What Is Renin? Blood Test & Low Renin Causes

Contents
  1. Plasma Renin Test Reveals the Contribution of Body Sodium-Volume Content (V) and Renin–Angiotensin (R) Vasoconstriction to Long-Term Blood Pressure
  2. Physiology and Pathophysiology of the Renin–Angiotensin System
  3. The Anti-V and Anti-R Antihypertensive Drug Types
  4. Studies That Led To the Volume-Vasoconstriction Analytical Model For Long-Term BP Control
  5. Body sodium content, PRA, and their interactive relationship to BP
  6. Renin
  7. Renin
  8. Renin
  9. Alternative Names
  10. Plasma Renin Test Reveals the Contribution of Body Sodium-Volume Content (V) and Renin–Angiotensin (R) Vasoconstriction to Long-Term Blood Pressure
  11. The interacting relationship between body sodium and the circulating renin–angiotensin system to maintain blood pressure, tissue blood flow, and tissue health. ACEI, angiotensin-converting enzyme inhibitor; Ang I, angiotensin I; ARB, angiotensin receptor blocker; BP, blood pressure; DRI, direct renin inhibitor; R, vasoconstrictor activity of the circulating renin–angiotensin system; V, body sodium-volume content
  12. Renin
  13. Alternative Names
  14. How the test is performed
  15. Plasma Renin Test Reveals the Contribution of Body Sodium-Volume Content (V) and Renin–Angiotensin (R) Vasoconstriction to Long-Term Blood Pressure
  16. The interacting relationship between body sodium and the circulating renin–angiotensin system to maintain blood pressure, tissue blood flow, and tissue health. ACEI, angiotensin-converting enzyme inhibitor; Ang I, angiotensin I; ARB, angiotensin receptor blocker; BP, blood pressure; DRI, direct renin inhibitor; R, vasoconstrictor activity of the circulating renin–angiotensin system; V, body sodium-volume content
  17. Physiology and Pathophysiology of the Renin–Angiotensin System
  18. The Anti-V and Anti-R Antihypertensive Drug Types
  19. Studies That Led To the Volume-Vasoconstriction Analytical Model For Long-Term BP Control
  20. Body sodium content, PRA, and their interactive relationship to BP
  21. Relationship of the 24-h urine sodium excretion (a reflection of the daily sodium intake) to the ambulatory plasma renin activity (PRA) level and to the 24-h urinary aldosterone excretion values in normal subjects (from Laragh et al.99). Because there were only three ambulatory PRA levels Source: https://academic.oup.com/ajh/article/24/11/1164/2281914 Renin Renin Renin is a protein (enzyme) released by special kidney cells when you have decreased salt (sodium levels) or low blood volume. Renin increases the amount of angiotensinogen in the blood, which eventually increases blood pressure. It increases the release of aldosterone, a hormone that helps control the body's salt and water balance. This article discusses the test to measure the activity of renin in your blood. Alternative Names Alternative Names Plasma renin activity; Random plasma renin; PRA How the test is performed How the test is performed A blood sample is needed. For information on how this is done, see: Venipuncture How to prepare for the test How to prepare for the test Your health care provider may tell you to temporarily stop taking certain drugs that can affect test results. Drugs that can affect renin measurements include: Birth control pills Blood pressure medications Diuretics Vasodilators (drugs that enlarge blood vessels; they are usually used to treat high blood pressure or congestive heart failure) You should eat a normal, balanced diet with moderate sodium content (about 3 gm/day) for 3 days before the test. How the test will feel How the test will feel When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing. Why the test is performed Why the test is performed This test is done as part of the diagnosis and treatment of high blood pressure. If you have essential hypertension, your doctor may order a renin and aldosterone test to see if you are sensitive to salt (which causes low renin with normal aldosterone levels). The test results may help to guide your doctor in choosing the correct medication. Salt-sensitive patients with high blood pressure associated with low renin levels respond well to diuretic medications. Normal Values Normal Values Normal values range from 0.2 to 3.3 ng/mL/hour. The examples above are common measurements for results of these tests. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your doctor about the meaning of your specific test results. What abnormal results mean What abnormal results mean High levels of renin may be due to: Addison's disease Cirrhosis Congestive heart failure Dehydration Hemorrhage (bleeding) High blood pressure Hypokalemia Malignant hypertension Nephrotic syndrome Renin-producing renal tumors Renovascular hypertension Low renin levels may be due to: ADH therapy Hyperaldosteronism Sodium-retaining steroid therapy High blood pressure that is sodium-sensitive What the risks are What the risks are Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others. Other risks associated with having blood drawn are slight but may include: Excessive bleeding Fainting or feeling lightheaded Hematoma (blood accumulating under the skin) Infection (a slight risk any time the skin is broken) Special considerations Special considerations Renin measurements are affected by salt intake, pregnancy, time of day, and body position. References Plasma Renin Test Reveals the Contribution of Body Sodium-Volume Content (V) and Renin–Angiotensin (R) Vasoconstriction to Long-Term Blood Pressure Body sodium works together with the plasma renin–angiotensin system to ensure adequate blood flow to the tissues. Body sodium content determines the extracellular fluid (ECF) volume ensuring that, with each heart beat, a sufficient volume of fluid is delivered into the arterial space. At the same time the kidneys monitor ECF volume and blood pressure (BP), so that the juxtaglomerular cells can adjust their net secretion rate of renin to maintain an appropriate plasma renin activity (PRA) level. Plasma renin produces angiotensin II (Ang II) to constrict the arterioles and thereby ensure sufficient BP to deliver an appropriate rate of flow for cardiovascular homeostasis. The low renin, sodium-volume dependent (V) form of essential hypertension occurs whenever body sodium content increases beyond the point where plasma renin–angiotensin vasoconstrictor activity is turned off. In contrast, medium to high renin (R) hypertension occurs when too much renin is secreted relative to the body sodium content. Thus, BP = V × R. This volume-vasoconstriction dual support of long-term hypertension is validated by the fact that all effective long-term antihypertensive drug types are either (i) natriuretic to reduce body salt and volume content (anti-V), or (ii) antirenin to reduce or block the activity of the circulating renin–angiotensin system (anti-R). The PRA test defines the relative participation of the concurrent volume and vasoconstrictor factors. In the hypertensive patient PRA testing can guide initiation, addition or subtraction of anti-V or anti-R antihypertensive drug types to thereby improve BP control and prognosis while reducing drug type usage and cost. American Journal of Hypertension, advance online publication 22 September 2011; doi:10.1038/ajh.2011.171 angiotensin, blood pressure, hypertension, plasma renin activity, plasma renin test, PRA, renin, salt, sodium, vasoconstriction, volume Dietary salt is often portrayed as a killer that causes high blood pressure (BP). At the same time renin is often portrayed as a villain that causes heart attacks, heart failure, renal failure, and strokes. To combat these problems salt is removed from diets, and diuretics and renin–angiotensin system blocking drugs are given. But these approaches ignore the fact that the body salt and the circulating renin–angiotensin system play pivotal roles in determining the level of BP, to sustain an appropriate flow of blood to the tissues and thereby ensure the delivery of nutrients and the removal of metabolic products (Figure 1). In this review, we describe how the plasma renin activity (PRA) test can be used to define the relative involvement of sodium-volume (V) and renin–angiotensin-vasoconstrictor (R) factors in determining BP, making it possible to identify whether a natriuretic anti-V or an antirenin–angiotensin anti-R drug is the correct drug type to effectively and efficiently treat the hypertension of the individual patient. The interacting relationship between body sodium and the circulating renin–angiotensin system to maintain blood pressure, tissue blood flow, and tissue health. ACEI, angiotensin-converting enzyme inhibitor; Ang I, angiotensin I; ARB, angiotensin receptor blocker; BP, blood pressure; DRI, direct renin inhibitor; R, vasoconstrictor activity of the circulating renin–angiotensin system; V, body sodium-volume content Open in new tabDownload slide Physiology and Pathophysiology of the Renin–Angiotensin System The physiological basis for the dual volume-vasoconstriction conception of BP control emerged from many years of clinical research. 1–4 It postulates that long-term BP–as opposed to minute to minute changes in BP–is sustained by two interacting forces: (i) the body sodium-volume content (V) and (ii) the plasma renin–angiotensin (R) vasoconstrictor activity. This V and R interacting control system sustains all normotension, as well as all forms of hypertension–regardless of initiating cause. This twin control of BP is in keeping with the long held view that arterial BP is sensitive to changes in body salt. It also recognizes that body salt does not affect BP directly but does so only by increasing or decreasing the extracellular fluid volume (ECF) and thus (assuming normal cardiac function) the volume of fluid delivered to the arterial tree. This, per se affects arterial BP via an hydraulic effect. In addition, compensatory adjustments in arteriolar caliber are mediated by companion changes in circulating angiotensin II (Ang II). This adjustment occurs whenever the cells of the renal juxtaglomerular apparatus of each nephron detect increases or decreases in body sodium-volume content and then alter their secretion of renin–downward or upward. The vasoconstrictor effects of the induced changes in plasma Ang II, generated by PRA, alter the caliber of the arterioles thereby ensuring that BP is not significantly affected by changes in arterial sodium-volume. Thus, changes in body salt content are buffered by reciprocal changes in PRA to maintain BP homeostasis. In the simplest of terms, arterial BP control can be viewed from the perspective of the 1828 Poiseuille equation: BP = cardiac output × peripheral resistance. In this equation the body sodium-volume content and PRA become functional surrogates for cardiac output and arteriolar resistance respectively: Thus, BP = (sodium-volume) × (PRA), or BP = V × R. In this model, irrespective of the particular BP level, the degree of vasoconstriction caused by the circulating renin–angiotensin system is always proportional to the concurrent PRA level. Thus, a normal BP level can be associated with low, medium or high PRA levels when it is concurrently associated with reciprocally high, medium or low levels of body sodium volume content respectively. From another perspective, the PRA level can be viewed as an index of whether the subject is salt depleted and hypovolemic, or instead is hypervolemic from a salt excess. A high PRA level in a normotensive individual indicates some degree of body sodium-volume depletion, whereas a low PRA level indicates that body sodium-volume status is on the high side. Long-term hypertension (as opposed to acute fluctuations in BP) occurs whenever the kidneys fail to induce a sufficient fall in PRA in response to an increase in body salt. Hypertension may occur because renin secretion is already maximally suppressed, or because there is a defect in juxtaglomerular apparatus sensing mechanisms of individual nephrons that allows too much renin to be secreted for the level of body salt, or because there is overactivity of the sympathetic drive to renin release. Whatever the reason, for hypertension to develop, PRA levels need not be higher than normal–just too high for the concurrent body sodium-volume content. This is why many hypertensive patients with renin-dependent hypertension exhibit PRA levels within the normal range. Moreover, the reciprocals are also true. Whenever BP is successfully controlled, angiotensin-mediated vasoconstriction returns toward the medium range, indicating the return to an appropriate relationship to the body sodium-volume content to achieve optimal tissue flow. The Anti-V and Anti-R Antihypertensive Drug Types A fundamental verifying corollary of this volume-vasoconstriction dual servo-control system for long-term BP regulation is the fact that all effective antihypertensive drugs lower BP by either (i) reducing the body sodium-volume content or (ii) by reducing or blocking the vasoconstrictor activity of the circulating renin–angiotensin system. 5 This fits the underlying pathophysiology because all effective long-term antihypertensive drugs also fall into one of two categories: they are either (i) natriuretic agents that reduce body sodium-volume content–the anti-V drug types (i.e. , sulfonamide diuretics, aldosterone receptor blockers, α-adrenergic blockers,6 calcium channel blockers7–9) or (ii) instead they reduce or block the vasoconstrictor activity of the circulating renin–angiotensin system–these are the antirenin system anti-R drugs (i.e., β-blockers, centrally acting agents (e.g. , clonidine, guanfacine, reserpine), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), direct renin inhibitors (e.g., aliskiren)). The classification of all available antihypertensive drugs into only two functional categories greatly simplifies drug treatment selection strategies because an enormous array of commercially available pharmaceutical agents (Table 1) and combinations thereof can be reduced to only two broad categories, either the natriuretic anti-V or the anti-R drugs (Table 2). This has enabled the development of relatively simple plasma renin-guided algorithms for the treatment of hypertension (discussed below). How does the health care professional choose among the ten classes and 66 or more individual antihypertensive drugs? The anti-V and anti-R categories of antihypertensive drugs Studies That Led To the Volume-Vasoconstriction Analytical Model For Long-Term BP Control These studies were grounded in Poisseuille's formula: (BP = cardiac output × peripheral resistance), in Tigerstedt's discovery of renin,10 in Goldblatt's renovascular model of hypertension,11 and in Conn's discovery of primary aldosteronism. 12 They matured as the biochemical components of the renin–angiotensin system were discovered,13 the sensing mechanisms of the renal juxtaglomerular apparatus were identified,14,15 and at a time when Guyton was identifying the over-riding dominance of the kidneys for sustaining hypertension.16 Body sodium content, PRA, and their interactive relationship to BP The existence of two pathophysiological types of long-term hypertension became apparent during studies of malignant hypertension and of primary aldosteronism that led to our discovery of the link between the circulating renin–angiotensin system and adrenal cortical aldosterone secretion. 17–19 It became clear that these two clinical forms of hypertension were quite different; malignant hypertensive patients were very sick and died within a year whereas those with primary aldosteronism remained relatively healthy. Thus, malignant hypertensive patients had very high levels of both plasma renin and the sodium-retaining hormone, aldosterone, whereas those with primary aldosteronism had very high aldosterone levels but very low plasma renin levels. 1,2 Thus, in more modern terms,5,20 malignant hypertension had both R and V hypertension, while primary aldosteronism had pure V hypertension with suppressed PRA. The inter-relationships between body sodium content and PRA were examined in 1970 when Bull et al. 21 separately manipulated body sodium content as well as plasma and red blood cell volumes in six normal volunteers, who first underwent dietary and diuretic induced sodium-volume depletion during which PRA and aldosterone levels rose in parallel. Then during dietary sodium repletion, PRA and aldosterone levels fell in parallel as urinary sodium excretion increased even though blood volume was held at low levels by daily plasmapheresis. These findings indicate that expansion or contraction of the extracellular space is a more important determinant of sodium conservation or natriuresis than is the plasma or blood volume. In this model, body sodium-volume content exists in the extracellular fluids and is created by retained sodium chloride ions which hold enough water in the body to ensure that the ECF is isotonic. The links between body sodium content and PRA were again revealed when urinary aldosterone excretion and PRA levels were measured in normal subjects (Figure 2) and in hypertensive patients during wide ranges of sodium intake and related to the 24-h urinary sodium excretion.22,23 Relationship of the 24-h urine sodium excretion (a reflection of the daily sodium intake) to the ambulatory plasma renin activity (PRA) level and to the 24-h urinary aldosterone excretion values in normal subjects (from Laragh et al.99). Because there were only three ambulatory PRA levels Source: https://academic.oup.com/ajh/article/24/11/1164/2281914 Renin Renin is a protein (enzyme) released by special kidney cells when you have decreased salt (sodium levels) or low blood volume. Renin increases the amount of angiotensinogen in the blood, which eventually increases blood pressure. It increases the release of aldosterone, a hormone that helps control the body's salt and water balance. This article discusses the test to measure the activity of renin in your blood. Alternative Names Plasma renin activity; Random plasma renin; PRA How the test is performed A blood sample is needed. For information on how this is done, see: Venipuncture How to prepare for the test Your health care provider may tell you to temporarily stop taking certain drugs that can affect test results. Drugs that can affect renin measurements include: Birth control pills Blood pressure medications Diuretics Vasodilators (drugs that enlarge blood vessels; they are usually used to treat high blood pressure or congestive heart failure) You should eat a normal, balanced diet with moderate sodium content (about 3 gm/day) for 3 days before the test. How the test will feel When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing. Why the test is performed This test is done as part of the diagnosis and treatment of high blood pressure. If you have essential hypertension, your doctor may order a renin and aldosterone test to see if you are sensitive to salt (which causes low renin with normal aldosterone levels). The test results may help to guide your doctor in choosing the correct medication. Salt-sensitive patients with high blood pressure associated with low renin levels respond well to diuretic medications. Normal Values Normal values range from 0.2 to 3.3 ng/mL/hour. The examples above are common measurements for results of these tests. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your doctor about the meaning of your specific test results. What abnormal results mean High levels of renin may be due to: Addison's disease Cirrhosis Congestive heart failure Dehydration Hemorrhage (bleeding) High blood pressure Hypokalemia Malignant hypertension Nephrotic syndrome Renin-producing renal tumors Renovascular hypertension Low renin levels may be due to: ADH therapy Hyperaldosteronism Sodium-retaining steroid therapy High blood pressure that is sodium-sensitive What the risks are Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others. Other risks associated with having blood drawn are slight but may include: Excessive bleeding Fainting or feeling lightheaded Hematoma (blood accumulating under the skin) Infection (a slight risk any time the skin is broken) Special considerations Renin measurements are affected by salt intake, pregnancy, time of day, and body position. Plasma Renin Test Reveals the Contribution of Body Sodium-Volume Content (V) and Renin–Angiotensin (R) Vasoconstriction to Long-Term Blood Pressure Body sodium works together with the plasma renin–angiotensin system to ensure adequate blood flow to the tissues. Body sodium content determines the extracellular fluid (ECF) volume ensuring that, with each heart beat, a sufficient volume of fluid is delivered into the arterial space. At the same time the kidneys monitor ECF volume and blood pressure (BP), so that the juxtaglomerular cells can adjust their net secretion rate of renin to maintain an appropriate plasma renin activity (PRA) level. Plasma renin produces angiotensin II (Ang II) to constrict the arterioles and thereby ensure sufficient BP to deliver an appropriate rate of flow for cardiovascular homeostasis. The low renin, sodium-volume dependent (V) form of essential hypertension occurs whenever body sodium content increases beyond the point where plasma renin–angiotensin vasoconstrictor activity is turned off. In contrast, medium to high renin (R) hypertension occurs when too much renin is secreted relative to the body sodium content. Thus, BP = V × R. This volume-vasoconstriction dual support of long-term hypertension is validated by the fact that all effective long-term antihypertensive drug types are either (i) natriuretic to reduce body salt and volume content (anti-V), or (ii) antirenin to reduce or block the activity of the circulating renin–angiotensin system (anti-R). The PRA test defines the relative participation of the concurrent volume and vasoconstrictor factors. In the hypertensive patient PRA testing can guide initiation, addition or subtraction of anti-V or anti-R antihypertensive drug types to thereby improve BP control and prognosis while reducing drug type usage and cost. American Journal of Hypertension, advance online publication 22 September 2011; doi:10.1038/ajh.2011.171 angiotensin, blood pressure, hypertension, plasma renin activity, plasma renin test, PRA, renin, salt, sodium, vasoconstriction, volume Dietary salt is often portrayed as a killer that causes high blood pressure (BP). At the same time renin is often portrayed as a villain that causes heart attacks, heart failure, renal failure, and strokes. To combat these problems salt is removed from diets, and diuretics and renin–angiotensin system blocking drugs are given. But these approaches ignore the fact that the body salt and the circulating renin–angiotensin system play pivotal roles in determining the level of BP, to sustain an appropriate flow of blood to the tissues and thereby ensure the delivery of nutrients and the removal of metabolic products (Figure 1). In this review, we describe how the plasma renin activity (PRA) test can be used to define the relative involvement of sodium-volume (V) and renin–angiotensin-vasoconstrictor (R) factors in determining BP, making it possible to identify whether a natriuretic anti-V or an antirenin–angiotensin anti-R drug is the correct drug type to effectively and efficiently treat the hypertension of the individual patient. The interacting relationship between body sodium and the circulating renin–angiotensin system to maintain blood pressure, tissue blood flow, and tissue health. ACEI, angiotensin-converting enzyme inhibitor; Ang I, angiotensin I; ARB, angiotensin receptor blocker; BP, blood pressure; DRI, direct renin inhibitor; R, vasoconstrictor activity of the circulating renin–angiotensin system; V, body sodium-volume content Open in new tabDownload slide Physiology and Pathophysiology of the Renin–Angiotensin System The physiological basis for the dual volume-vasoconstriction conception of BP control emerged from many years of clinical research. 1–4 It postulates that long-term BP–as opposed to minute to minute changes in BP–is sustained by two interacting forces: (i) the body sodium-volume content (V) and (ii) the plasma renin–angiotensin (R) vasoconstrictor activity. This V and R interacting control system sustains all normotension, as well as all forms of hypertension–regardless of initiating cause. This twin control of BP is in keeping with the long held view that arterial BP is sensitive to changes in body salt. It also recognizes that body salt does not affect BP directly but does so only by increasing or decreasing the extracellular fluid volume (ECF) and thus (assuming normal cardiac function) the volume of fluid delivered to the arterial tree. This, per se affects arterial BP via an hydraulic effect. In addition, compensatory adjustments in arteriolar caliber are mediated by companion changes in circulating angiotensin II (Ang II). This adjustment occurs whenever the cells of the renal juxtaglomerular apparatus of each nephron detect increases or decreases in body sodium-volume content and then alter their secretion of renin–downward or upward. The vasoconstrictor effects of the induced changes in plasma Ang II, generated by PRA, alter the caliber of the arterioles thereby ensuring that BP is not significantly affected by changes in arterial sodium-volume. Thus, changes in body salt content are buffered by reciprocal changes in PRA to maintain BP homeostasis. In the simplest of terms, arterial BP control can be viewed from the perspective of the 1828 Poiseuille equation: BP = cardiac output × peripheral resistance. In this equation the body sodium-volume content and PRA become functional surrogates for cardiac output and arteriolar resistance respectively: Thus, BP = (sodium-volume) × (PRA), or BP = V × R. In this model, irrespective of the particular BP level, the degree of vasoconstriction caused by the circulating renin–angiotensin system is always proportional to the concurrent PRA level. Thus, a normal BP level can be associated with low, medium or high PRA levels when it is concurrently associated with reciprocally high, medium or low levels of body sodium volume content respectively. From another perspective, the PRA level can be viewed as an index of whether the subject is salt depleted and hypovolemic, or instead is hypervolemic from a salt excess. A high PRA level in a normotensive individual indicates some degree of body sodium-volume depletion, whereas a low PRA level indicates that body sodium-volume status is on the high side. Long-term hypertension (as opposed to acute fluctuations in BP) occurs whenever the kidneys fail to induce a sufficient fall in PRA in response to an increase in body salt. Hypertension may occur because renin secretion is already maximally suppressed, or because there is a defect in juxtaglomerular apparatus sensing mechanisms of individual nephrons that allows too much renin to be secreted for the level of body salt, or because there is overactivity of the sympathetic drive to renin release. Whatever the reason, for hypertension to develop, PRA levels need not be higher than normal–just too high for the concurrent body sodium-volume content. This is why many hypertensive patients with renin-dependent hypertension exhibit PRA levels within the normal range. Moreover, the reciprocals are also true. Whenever BP is successfully controlled, angiotensin-mediated vasoconstriction returns toward the medium range, indicating the return to an appropriate relationship to the body sodium-volume content to achieve optimal tissue flow. The Anti-V and Anti-R Antihypertensive Drug Types A fundamental verifying corollary of this volume-vasoconstriction dual servo-control system for long-term BP regulation is the fact that all effective antihypertensive drugs lower BP by either (i) reducing the body sodium-volume content or (ii) by reducing or blocking the vasoconstrictor activity of the circulating renin–angiotensin system. 5 This fits the underlying pathophysiology because all effective long-term antihypertensive drugs also fall into one of two categories: they are either (i) natriuretic agents that reduce body sodium-volume content–the anti-V drug types (i.e. , sulfonamide diuretics, aldosterone receptor blockers, α-adrenergic blockers,6 calcium channel blockers7–9) or (ii) instead they reduce or block the vasoconstrictor activity of the circulating renin–angiotensin system–these are the antirenin system anti-R drugs (i.e., β-blockers, centrally acting agents (e.g. , clonidine, guanfacine, reserpine), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), direct renin inhibitors (e.g., aliskiren)). The classification of all available antihypertensive drugs into only two functional categories greatly simplifies drug treatment selection strategies because an enormous array of commercially available pharmaceutical agents (Table 1) and combinations thereof can be reduced to only two broad categories, either the natriuretic anti-V or the anti-R drugs (Table 2). This has enabled the development of relatively simple plasma renin-guided algorithms for the treatment of hypertension (discussed below). How does the health care professional choose among the ten classes and 66 or more individual antihypertensive drugs? The anti-V and anti-R categories of antihypertensive drugs Studies That Led To the Volume-Vasoconstriction Analytical Model For Long-Term BP Control These studies were grounded in Poisseuille's formula: (BP = cardiac output × peripheral resistance), in Tigerstedt's discovery of renin,10 in Goldblatt's renovascular model of hypertension,11 and in Conn's discovery of primary aldosteronism. 12 They matured as the biochemical components of the renin–angiotensin system were discovered,13 the sensing mechanisms of the renal juxtaglomerular apparatus were identified,14,15 and at a time when Guyton was identifying the over-riding dominance of the kidneys for sustaining hypertension.16 Body sodium content, PRA, and their interactive relationship to BP The existence of two pathophysiological types of long-term hypertension became apparent during studies of malignant hypertension and of primary aldosteronism that led to our discovery of the link between the circulating renin–angiotensin system and adrenal cortical aldosterone secretion. 17–19 It became clear that these two clinical forms of hypertension were quite different; malignant hypertensive patients were very sick and died within a year whereas those with primary aldosteronism remained relatively healthy. Thus, malignant hypertensive patients had very high levels of both plasma renin and the sodium-retaining hormone, aldosterone, whereas those with primary aldosteronism had very high aldosterone levels but very low plasma renin levels. 1,2 Thus, in more modern terms,5,20 malignant hypertension had both R and V hypertension, while primary aldosteronism had pure V hypertension with suppressed PRA. The inter-relationships between body sodium content and PRA were examined in 1970 when Bull et al. 21 separately manipulated body sodium content as well as plasma and red blood cell volumes in six normal volunteers, who first underwent dietary and diuretic induced sodium-volume depletion during which PRA and aldosterone levels rose in parallel. Then during dietary sodium repletion, PRA and aldosterone levels fell in parallel as urinary sodium excretion increased even though blood volume was held at low levels by daily plasmapheresis. These findings indicate that expansion or contraction of the extracellular space is a more important determinant of sodium conservation or natriuresis than is the plasma or blood volume. In this model, body sodium-volume content exists in the extracellular fluids and is created by retained sodium chloride ions which hold enough water in the body to ensure that the ECF is isotonic. The links between body sodium content and PRA were again revealed when urinary aldosterone excretion and PRA levels were measured in normal subjects (Figure 2) and in hypertensive patients during wide ranges of sodium intake and related to the 24-h urinary sodium excretion.22,23 Relationship of the 24-h urine sodium excretion (a reflection of the daily sodium intake) to the ambulatory plasma renin activity (PRA) level and to the 24-h urinary aldosterone excretion values in normal subjects (from Laragh et al.99). Because there were only three ambulatory PRA levels Source: https://academic.oup.com/ajh/article/24/11/1164/2281914 Renin Renin Renin is a protein (enzyme) released by special kidney cells when you have decreased salt (sodium levels) or low blood volume. Renin increases the amount of angiotensinogen in the blood, which eventually increases blood pressure. It increases the release of aldosterone, a hormone that helps control the body's salt and water balance. This article discusses the test to measure the activity of renin in your blood. Alternative Names Alternative Names Plasma renin activity; Random plasma renin; PRA How the test is performed How the test is performed A blood sample is needed. For information on how this is done, see: Venipuncture How to prepare for the test How to prepare for the test Your health care provider may tell you to temporarily stop taking certain drugs that can affect test results. Drugs that can affect renin measurements include: Birth control pills Blood pressure medications Diuretics Vasodilators (drugs that enlarge blood vessels; they are usually used to treat high blood pressure or congestive heart failure) You should eat a normal, balanced diet with moderate sodium content (about 3 gm/day) for 3 days before the test. How the test will feel How the test will feel When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing. Why the test is performed Why the test is performed This test is done as part of the diagnosis and treatment of high blood pressure. If you have essential hypertension, your doctor may order a renin and aldosterone test to see if you are sensitive to salt (which causes low renin with normal aldosterone levels). The test results may help to guide your doctor in choosing the correct medication. Salt-sensitive patients with high blood pressure associated with low renin levels respond well to diuretic medications. Normal Values Normal Values Normal values range from 0.2 to 3.3 ng/mL/hour. The examples above are common measurements for results of these tests. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your doctor about the meaning of your specific test results. What abnormal results mean What abnormal results mean High levels of renin may be due to: Addison's disease Cirrhosis Congestive heart failure Dehydration Hemorrhage (bleeding) High blood pressure Hypokalemia Malignant hypertension Nephrotic syndrome Renin-producing renal tumors Renovascular hypertension Low renin levels may be due to: ADH therapy Hyperaldosteronism Sodium-retaining steroid therapy High blood pressure that is sodium-sensitive What the risks are What the risks are Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others. Other risks associated with having blood drawn are slight but may include: Excessive bleeding Fainting or feeling lightheaded Hematoma (blood accumulating under the skin) Infection (a slight risk any time the skin is broken) Special considerations Special considerations Renin measurements are affected by salt intake, pregnancy, time of day, and body position. References Plasma Renin Test Reveals the Contribution of Body Sodium-Volume Content (V) and Renin–Angiotensin (R) Vasoconstriction to Long-Term Blood Pressure Body sodium works together with the plasma renin–angiotensin system to ensure adequate blood flow to the tissues. Body sodium content determines the extracellular fluid (ECF) volume ensuring that, with each heart beat, a sufficient volume of fluid is delivered into the arterial space. At the same time the kidneys monitor ECF volume and blood pressure (BP), so that the juxtaglomerular cells can adjust their net secretion rate of renin to maintain an appropriate plasma renin activity (PRA) level. Plasma renin produces angiotensin II (Ang II) to constrict the arterioles and thereby ensure sufficient BP to deliver an appropriate rate of flow for cardiovascular homeostasis. The low renin, sodium-volume dependent (V) form of essential hypertension occurs whenever body sodium content increases beyond the point where plasma renin–angiotensin vasoconstrictor activity is turned off. In contrast, medium to high renin (R) hypertension occurs when too much renin is secreted relative to the body sodium content. Thus, BP = V × R. This volume-vasoconstriction dual support of long-term hypertension is validated by the fact that all effective long-term antihypertensive drug types are either (i) natriuretic to reduce body salt and volume content (anti-V), or (ii) antirenin to reduce or block the activity of the circulating renin–angiotensin system (anti-R). The PRA test defines the relative participation of the concurrent volume and vasoconstrictor factors. In the hypertensive patient PRA testing can guide initiation, addition or subtraction of anti-V or anti-R antihypertensive drug types to thereby improve BP control and prognosis while reducing drug type usage and cost. American Journal of Hypertension, advance online publication 22 September 2011; doi:10.1038/ajh.2011.171 angiotensin, blood pressure, hypertension, plasma renin activity, plasma renin test, PRA, renin, salt, sodium, vasoconstriction, volume Dietary salt is often portrayed as a killer that causes high blood pressure (BP). At the same time renin is often portrayed as a villain that causes heart attacks, heart failure, renal failure, and strokes. To combat these problems salt is removed from diets, and diuretics and renin–angiotensin system blocking drugs are given. But these approaches ignore the fact that the body salt and the circulating renin–angiotensin system play pivotal roles in determining the level of BP, to sustain an appropriate flow of blood to the tissues and thereby ensure the delivery of nutrients and the removal of metabolic products (Figure 1). In this review, we describe how the plasma renin activity (PRA) test can be used to define the relative involvement of sodium-volume (V) and renin–angiotensin-vasoconstrictor (R) factors in determining BP, making it possible to identify whether a natriuretic anti-V or an antirenin–angiotensin anti-R drug is the correct drug type to effectively and efficiently treat the hypertension of the individual patient. The interacting relationship between body sodium and the circulating renin–angiotensin system to maintain blood pressure, tissue blood flow, and tissue health. ACEI, angiotensin-converting enzyme inhibitor; Ang I, angiotensin I; ARB, angiotensin receptor blocker; BP, blood pressure; DRI, direct renin inhibitor; R, vasoconstrictor activity of the circulating renin–angiotensin system; V, body sodium-volume content Open in new tabDownload slide Physiology and Pathophysiology of the Renin–Angiotensin System The physiological basis for the dual volume-vasoconstriction conception of BP control emerged from many years of clinical research. 1–4 It postulates that long-term BP–as opposed to minute to minute changes in BP–is sustained by two interacting forces: (i) the body sodium-volume content (V) and (ii) the plasma renin–angiotensin (R) vasoconstrictor activity. This V and R interacting control system sustains all normotension, as well as all forms of hypertension–regardless of initiating cause. This twin control of BP is in keeping with the long held view that arterial BP is sensitive to changes in body salt. It also recognizes that body salt does not affect BP directly but does so only by increasing or decreasing the extracellular fluid volume (ECF) and thus (assuming normal cardiac function) the volume of fluid delivered to the arterial tree. This, per se affects arterial BP via an hydraulic effect. In addition, compensatory adjustments in arteriolar caliber are mediated by companion changes in circulating angiotensin II (Ang II). This adjustment occurs whenever the cells of the renal juxtaglomerular apparatus of each nephron detect increases or decreases in body sodium-volume content and then alter their secretion of renin–downward or upward. The vasoconstrictor effects of the induced changes in plasma Ang II, generated by PRA, alter the caliber of the arterioles thereby ensuring that BP is not significantly affected by changes in arterial sodium-volume. Thus, changes in body salt content are buffered by reciprocal changes in PRA to maintain BP homeostasis. In the simplest of terms, arterial BP control can be viewed from the perspective of the 1828 Poiseuille equation: BP = cardiac output × peripheral resistance. In this equation the body sodium-volume content and PRA become functional surrogates for cardiac output and arteriolar resistance respectively: Thus, BP = (sodium-volume) × (PRA), or BP = V × R. In this model, irrespective of the particular BP level, the degree of vasoconstriction caused by the circulating renin–angiotensin system is always proportional to the concurrent PRA level. Thus, a normal BP level can be associated with low, medium or high PRA levels when it is concurrently associated with reciprocally high, medium or low levels of body sodium volume content respectively. From another perspective, the PRA level can be viewed as an index of whether the subject is salt depleted and hypovolemic, or instead is hypervolemic from a salt excess. A high PRA level in a normotensive individual indicates some degree of body sodium-volume depletion, whereas a low PRA level indicates that body sodium-volume status is on the high side. Long-term hypertension (as opposed to acute fluctuations in BP) occurs whenever the kidneys fail to induce a sufficient fall in PRA in response to an increase in body salt. Hypertension may occur because renin secretion is already maximally suppressed, or because there is a defect in juxtaglomerular apparatus sensing mechanisms of individual nephrons that allows too much renin to be secreted for the level of body salt, or because there is overactivity of the sympathetic drive to renin release. Whatever the reason, for hypertension to develop, PRA levels need not be higher than normal–just too high for the concurrent body sodium-volume content. This is why many hypertensive patients with renin-dependent hypertension exhibit PRA levels within the normal range. Moreover, the reciprocals are also true. Whenever BP is successfully controlled, angiotensin-mediated vasoconstriction returns toward the medium range, indicating the return to an appropriate relationship to the body sodium-volume content to achieve optimal tissue flow. The Anti-V and Anti-R Antihypertensive Drug Types A fundamental verifying corollary of this volume-vasoconstriction dual servo-control system for long-term BP regulation is the fact that all effective antihypertensive drugs lower BP by either (i) reducing the body sodium-volume content or (ii) by reducing or blocking the vasoconstrictor activity of the circulating renin–angiotensin system. 5 This fits the underlying pathophysiology because all effective long-term antihypertensive drugs also fall into one of two categories: they are either (i) natriuretic agents that reduce body sodium-volume content–the anti-V drug types (i.e. , sulfonamide diuretics, aldosterone receptor blockers, α-adrenergic blockers,6 calcium channel blockers7–9) or (ii) instead they reduce or block the vasoconstrictor activity of the circulating renin–angiotensin system–these are the antirenin system anti-R drugs (i.e., β-blockers, centrally acting agents (e.g. , clonidine, guanfacine, reserpine), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), direct renin inhibitors (e.g., aliskiren)). The classification of all available antihypertensive drugs into only two functional categories greatly simplifies drug treatment selection strategies because an enormous array of commercially available pharmaceutical agents (Table 1) and combinations thereof can be reduced to only two broad categories, either the natriuretic anti-V or the anti-R drugs (Table 2). This has enabled the development of relatively simple plasma renin-guided algorithms for the treatment of hypertension (discussed below). How does the health care professional choose among the ten classes and 66 or more individual antihypertensive drugs? The anti-V and anti-R categories of antihypertensive drugs Studies That Led To the Volume-Vasoconstriction Analytical Model For Long-Term BP Control These studies were grounded in Poisseuille's formula: (BP = cardiac output × peripheral resistance), in Tigerstedt's discovery of renin,10 in Goldblatt's renovascular model of hypertension,11 and in Conn's discovery of primary aldosteronism. 12 They matured as the biochemical components of the renin–angiotensin system were discovered,13 the sensing mechanisms of the renal juxtaglomerular apparatus were identified,14,15 and at a time when Guyton was identifying the over-riding dominance of the kidneys for sustaining hypertension.16 Body sodium content, PRA, and their interactive relationship to BP The existence of two pathophysiological types of long-term hypertension became apparent during studies of malignant hypertension and of primary aldosteronism that led to our discovery of the link between the circulating renin–angiotensin system and adrenal cortical aldosterone secretion. 17–19 It became clear that these two clinical forms of hypertension were quite different; malignant hypertensive patients were very sick and died within a year whereas those with primary aldosteronism remained relatively healthy. Thus, malignant hypertensive patients had very high levels of both plasma renin and the sodium-retaining hormone, aldosterone, whereas those with primary aldosteronism had very high aldosterone levels but very low plasma renin levels. 1,2 Thus, in more modern terms,5,20 malignant hypertension had both R and V hypertension, while primary aldosteronism had pure V hypertension with suppressed PRA. The inter-relationships between body sodium content and PRA were examined in 1970 when Bull et al. 21 separately manipulated body sodium content as well as plasma and red blood cell volumes in six normal volunteers, who first underwent dietary and diuretic induced sodium-volume depletion during which PRA and aldosterone levels rose in parallel. Then during dietary sodium repletion, PRA and aldosterone levels fell in parallel as urinary sodium excretion increased even though blood volume was held at low levels by daily plasmapheresis. These findings indicate that expansion or contraction of the extracellular space is a more important determinant of sodium conservation or natriuresis than is the plasma or blood volume. In this model, body sodium-volume content exists in the extracellular fluids and is created by retained sodium chloride ions which hold enough water in the body to ensure that the ECF is isotonic. The links between body sodium content and PRA were again revealed when urinary aldosterone excretion and PRA levels were measured in normal subjects (Figure 2) and in hypertensive patients during wide ranges of sodium intake and related to the 24-h urinary sodium excretion.22,23 Relationship of the 24-h urine sodium excretion (a reflection of the daily sodium intake) to the ambulatory plasma renin activity (PRA) level and to the 24-h urinary aldosterone excretion values in normal subjects (from Laragh et al.99). Because there were only three ambulatory PRA levels Source: https://academic.oup.com/ajh/article/24/11/1164/2281914 Renin Renin is a protein (enzyme) released by special kidney cells when you have decreased salt (sodium levels) or low blood volume. Renin increases the amount of angiotensinogen in the blood, which eventually increases blood pressure. It increases the release of aldosterone, a hormone that helps control the body's salt and water balance. This article discusses the test to measure the activity of renin in your blood. Alternative Names Plasma renin activity; Random plasma renin; PRA How the test is performed A blood sample is needed. For information on how this is done, see: Venipuncture How to prepare for the test Your health care provider may tell you to temporarily stop taking certain drugs that can affect test results. Drugs that can affect renin measurements include: Birth control pills Blood pressure medications Diuretics Vasodilators (drugs that enlarge blood vessels; they are usually used to treat high blood pressure or congestive heart failure) You should eat a normal, balanced diet with moderate sodium content (about 3 gm/day) for 3 days before the test. How the test will feel When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing. Why the test is performed This test is done as part of the diagnosis and treatment of high blood pressure. If you have essential hypertension, your doctor may order a renin and aldosterone test to see if you are sensitive to salt (which causes low renin with normal aldosterone levels). The test results may help to guide your doctor in choosing the correct medication. Salt-sensitive patients with high blood pressure associated with low renin levels respond well to diuretic medications. Normal Values Normal values range from 0.2 to 3.3 ng/mL/hour. The examples above are common measurements for results of these tests. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your doctor about the meaning of your specific test results. What abnormal results mean High levels of renin may be due to: Addison's disease Cirrhosis Congestive heart failure Dehydration Hemorrhage (bleeding) High blood pressure Hypokalemia Malignant hypertension Nephrotic syndrome Renin-producing renal tumors Renovascular hypertension Low renin levels may be due to: ADH therapy Hyperaldosteronism Sodium-retaining steroid therapy High blood pressure that is sodium-sensitive What the risks are Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others. Other risks associated with having blood drawn are slight but may include: Excessive bleeding Fainting or feeling lightheaded Hematoma (blood accumulating under the skin) Infection (a slight risk any time the skin is broken) Special considerations Renin measurements are affected by salt intake, pregnancy, time of day, and body position. References Victor RG. Arterial hypertension. In: Goldman L, Schafer AI, eds. Cecil Medicine. 24th ed. Philadelphia, Pa: Saunders Elsevier; 2011:chap 67. Blumenfeld JD, Liu F, Laragh JR. Primary and secondary hypertension. In: Taal MW, Chertow GM, Marsden PA, Skorecki K, Yu ASL, Brenner BM, eds. Brenner & Rector's The Kidney. 9th ed. Philadelphia, PA: Saunders Elsevier; 2011:chap 46. Review Date: 9/3/2012 The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed physician should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only — they do not constitute endorsements of those other sites. Copyright ©2003 A.D.A.M., Inc., as modified by University of California San Francisco. Any duplication or distribution of the information contained herein is strictly prohibited. Information developed by A.D.A.M., Inc. regarding tests and test results may not directly correspond with information provided by UCSF Medical Center. Please discuss with your doctor any questions or concerns you may have. Source: https://www.ucsfbenioffchildrens.org/tests/003698.html
  22. Renin
  23. Renin
  24. Alternative Names
  25. Alternative Names
  26. How the test is performed
  27. How the test is performed
  28. How to prepare for the test
  29. How to prepare for the test
  30. How the test will feel
  31. How the test will feel
  32. Why the test is performed
  33. Why the test is performed
  34. Normal Values
  35. Normal Values
  36. What abnormal results mean
  37. What abnormal results mean
  38. What the risks are
  39. What the risks are
  40. Special considerations
  41. Special considerations
  42. References
  43. Plasma Renin Test Reveals the Contribution of Body Sodium-Volume Content (V) and Renin–Angiotensin (R) Vasoconstriction to Long-Term Blood Pressure
  44. The interacting relationship between body sodium and the circulating renin–angiotensin system to maintain blood pressure, tissue blood flow, and tissue health. ACEI, angiotensin-converting enzyme inhibitor; Ang I, angiotensin I; ARB, angiotensin receptor blocker; BP, blood pressure; DRI, direct renin inhibitor; R, vasoconstrictor activity of the circulating renin–angiotensin system; V, body sodium-volume content
  45. Physiology and Pathophysiology of the Renin–Angiotensin System
  46. The Anti-V and Anti-R Antihypertensive Drug Types
  47. Studies That Led To the Volume-Vasoconstriction Analytical Model For Long-Term BP Control
  48. Body sodium content, PRA, and their interactive relationship to BP
  49. Relationship of the 24-h urine sodium excretion (a reflection of the daily sodium intake) to the ambulatory plasma renin activity (PRA) level and to the 24-h urinary aldosterone excretion values in normal subjects (from Laragh et al.99). Because there were only three ambulatory PRA levels Source: https://academic.oup.com/ajh/article/24/11/1164/2281914 Renin Renin is a protein (enzyme) released by special kidney cells when you have decreased salt (sodium levels) or low blood volume. Renin increases the amount of angiotensinogen in the blood, which eventually increases blood pressure. It increases the release of aldosterone, a hormone that helps control the body's salt and water balance. This article discusses the test to measure the activity of renin in your blood. Alternative Names Plasma renin activity; Random plasma renin; PRA How the test is performed A blood sample is needed. For information on how this is done, see: Venipuncture How to prepare for the test Your health care provider may tell you to temporarily stop taking certain drugs that can affect test results. Drugs that can affect renin measurements include: Birth control pills Blood pressure medications Diuretics Vasodilators (drugs that enlarge blood vessels; they are usually used to treat high blood pressure or congestive heart failure) You should eat a normal, balanced diet with moderate sodium content (about 3 gm/day) for 3 days before the test. How the test will feel When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing. Why the test is performed This test is done as part of the diagnosis and treatment of high blood pressure. If you have essential hypertension, your doctor may order a renin and aldosterone test to see if you are sensitive to salt (which causes low renin with normal aldosterone levels). The test results may help to guide your doctor in choosing the correct medication. Salt-sensitive patients with high blood pressure associated with low renin levels respond well to diuretic medications. Normal Values Normal values range from 0.2 to 3.3 ng/mL/hour. The examples above are common measurements for results of these tests. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your doctor about the meaning of your specific test results. What abnormal results mean High levels of renin may be due to: Addison's disease Cirrhosis Congestive heart failure Dehydration Hemorrhage (bleeding) High blood pressure Hypokalemia Malignant hypertension Nephrotic syndrome Renin-producing renal tumors Renovascular hypertension Low renin levels may be due to: ADH therapy Hyperaldosteronism Sodium-retaining steroid therapy High blood pressure that is sodium-sensitive What the risks are Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others. Other risks associated with having blood drawn are slight but may include: Excessive bleeding Fainting or feeling lightheaded Hematoma (blood accumulating under the skin) Infection (a slight risk any time the skin is broken) Special considerations Renin measurements are affected by salt intake, pregnancy, time of day, and body position. Plasma Renin Test Reveals the Contribution of Body Sodium-Volume Content (V) and Renin–Angiotensin (R) Vasoconstriction to Long-Term Blood Pressure Body sodium works together with the plasma renin–angiotensin system to ensure adequate blood flow to the tissues. Body sodium content determines the extracellular fluid (ECF) volume ensuring that, with each heart beat, a sufficient volume of fluid is delivered into the arterial space. At the same time the kidneys monitor ECF volume and blood pressure (BP), so that the juxtaglomerular cells can adjust their net secretion rate of renin to maintain an appropriate plasma renin activity (PRA) level. Plasma renin produces angiotensin II (Ang II) to constrict the arterioles and thereby ensure sufficient BP to deliver an appropriate rate of flow for cardiovascular homeostasis. The low renin, sodium-volume dependent (V) form of essential hypertension occurs whenever body sodium content increases beyond the point where plasma renin–angiotensin vasoconstrictor activity is turned off. In contrast, medium to high renin (R) hypertension occurs when too much renin is secreted relative to the body sodium content. Thus, BP = V × R. This volume-vasoconstriction dual support of long-term hypertension is validated by the fact that all effective long-term antihypertensive drug types are either (i) natriuretic to reduce body salt and volume content (anti-V), or (ii) antirenin to reduce or block the activity of the circulating renin–angiotensin system (anti-R). The PRA test defines the relative participation of the concurrent volume and vasoconstrictor factors. In the hypertensive patient PRA testing can guide initiation, addition or subtraction of anti-V or anti-R antihypertensive drug types to thereby improve BP control and prognosis while reducing drug type usage and cost. American Journal of Hypertension, advance online publication 22 September 2011; doi:10.1038/ajh.2011.171 angiotensin, blood pressure, hypertension, plasma renin activity, plasma renin test, PRA, renin, salt, sodium, vasoconstriction, volume Dietary salt is often portrayed as a killer that causes high blood pressure (BP). At the same time renin is often portrayed as a villain that causes heart attacks, heart failure, renal failure, and strokes. To combat these problems salt is removed from diets, and diuretics and renin–angiotensin system blocking drugs are given. But these approaches ignore the fact that the body salt and the circulating renin–angiotensin system play pivotal roles in determining the level of BP, to sustain an appropriate flow of blood to the tissues and thereby ensure the delivery of nutrients and the removal of metabolic products (Figure 1). In this review, we describe how the plasma renin activity (PRA) test can be used to define the relative involvement of sodium-volume (V) and renin–angiotensin-vasoconstrictor (R) factors in determining BP, making it possible to identify whether a natriuretic anti-V or an antirenin–angiotensin anti-R drug is the correct drug type to effectively and efficiently treat the hypertension of the individual patient. The interacting relationship between body sodium and the circulating renin–angiotensin system to maintain blood pressure, tissue blood flow, and tissue health. ACEI, angiotensin-converting enzyme inhibitor; Ang I, angiotensin I; ARB, angiotensin receptor blocker; BP, blood pressure; DRI, direct renin inhibitor; R, vasoconstrictor activity of the circulating renin–angiotensin system; V, body sodium-volume content Open in new tabDownload slide Physiology and Pathophysiology of the Renin–Angiotensin System The physiological basis for the dual volume-vasoconstriction conception of BP control emerged from many years of clinical research. 1–4 It postulates that long-term BP–as opposed to minute to minute changes in BP–is sustained by two interacting forces: (i) the body sodium-volume content (V) and (ii) the plasma renin–angiotensin (R) vasoconstrictor activity. This V and R interacting control system sustains all normotension, as well as all forms of hypertension–regardless of initiating cause. This twin control of BP is in keeping with the long held view that arterial BP is sensitive to changes in body salt. It also recognizes that body salt does not affect BP directly but does so only by increasing or decreasing the extracellular fluid volume (ECF) and thus (assuming normal cardiac function) the volume of fluid delivered to the arterial tree. This, per se affects arterial BP via an hydraulic effect. In addition, compensatory adjustments in arteriolar caliber are mediated by companion changes in circulating angiotensin II (Ang II). This adjustment occurs whenever the cells of the renal juxtaglomerular apparatus of each nephron detect increases or decreases in body sodium-volume content and then alter their secretion of renin–downward or upward. The vasoconstrictor effects of the induced changes in plasma Ang II, generated by PRA, alter the caliber of the arterioles thereby ensuring that BP is not significantly affected by changes in arterial sodium-volume. Thus, changes in body salt content are buffered by reciprocal changes in PRA to maintain BP homeostasis. In the simplest of terms, arterial BP control can be viewed from the perspective of the 1828 Poiseuille equation: BP = cardiac output × peripheral resistance. In this equation the body sodium-volume content and PRA become functional surrogates for cardiac output and arteriolar resistance respectively: Thus, BP = (sodium-volume) × (PRA), or BP = V × R. In this model, irrespective of the particular BP level, the degree of vasoconstriction caused by the circulating renin–angiotensin system is always proportional to the concurrent PRA level. Thus, a normal BP level can be associated with low, medium or high PRA levels when it is concurrently associated with reciprocally high, medium or low levels of body sodium volume content respectively. From another perspective, the PRA level can be viewed as an index of whether the subject is salt depleted and hypovolemic, or instead is hypervolemic from a salt excess. A high PRA level in a normotensive individual indicates some degree of body sodium-volume depletion, whereas a low PRA level indicates that body sodium-volume status is on the high side. Long-term hypertension (as opposed to acute fluctuations in BP) occurs whenever the kidneys fail to induce a sufficient fall in PRA in response to an increase in body salt. Hypertension may occur because renin secretion is already maximally suppressed, or because there is a defect in juxtaglomerular apparatus sensing mechanisms of individual nephrons that allows too much renin to be secreted for the level of body salt, or because there is overactivity of the sympathetic drive to renin release. Whatever the reason, for hypertension to develop, PRA levels need not be higher than normal–just too high for the concurrent body sodium-volume content. This is why many hypertensive patients with renin-dependent hypertension exhibit PRA levels within the normal range. Moreover, the reciprocals are also true. Whenever BP is successfully controlled, angiotensin-mediated vasoconstriction returns toward the medium range, indicating the return to an appropriate relationship to the body sodium-volume content to achieve optimal tissue flow. The Anti-V and Anti-R Antihypertensive Drug Types A fundamental verifying corollary of this volume-vasoconstriction dual servo-control system for long-term BP regulation is the fact that all effective antihypertensive drugs lower BP by either (i) reducing the body sodium-volume content or (ii) by reducing or blocking the vasoconstrictor activity of the circulating renin–angiotensin system. 5 This fits the underlying pathophysiology because all effective long-term antihypertensive drugs also fall into one of two categories: they are either (i) natriuretic agents that reduce body sodium-volume content–the anti-V drug types (i.e. , sulfonamide diuretics, aldosterone receptor blockers, α-adrenergic blockers,6 calcium channel blockers7–9) or (ii) instead they reduce or block the vasoconstrictor activity of the circulating renin–angiotensin system–these are the antirenin system anti-R drugs (i.e., β-blockers, centrally acting agents (e.g. , clonidine, guanfacine, reserpine), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), direct renin inhibitors (e.g., aliskiren)). The classification of all available antihypertensive drugs into only two functional categories greatly simplifies drug treatment selection strategies because an enormous array of commercially available pharmaceutical agents (Table 1) and combinations thereof can be reduced to only two broad categories, either the natriuretic anti-V or the anti-R drugs (Table 2). This has enabled the development of relatively simple plasma renin-guided algorithms for the treatment of hypertension (discussed below). How does the health care professional choose among the ten classes and 66 or more individual antihypertensive drugs? The anti-V and anti-R categories of antihypertensive drugs Studies That Led To the Volume-Vasoconstriction Analytical Model For Long-Term BP Control These studies were grounded in Poisseuille's formula: (BP = cardiac output × peripheral resistance), in Tigerstedt's discovery of renin,10 in Goldblatt's renovascular model of hypertension,11 and in Conn's discovery of primary aldosteronism. 12 They matured as the biochemical components of the renin–angiotensin system were discovered,13 the sensing mechanisms of the renal juxtaglomerular apparatus were identified,14,15 and at a time when Guyton was identifying the over-riding dominance of the kidneys for sustaining hypertension.16 Body sodium content, PRA, and their interactive relationship to BP The existence of two pathophysiological types of long-term hypertension became apparent during studies of malignant hypertension and of primary aldosteronism that led to our discovery of the link between the circulating renin–angiotensin system and adrenal cortical aldosterone secretion. 17–19 It became clear that these two clinical forms of hypertension were quite different; malignant hypertensive patients were very sick and died within a year whereas those with primary aldosteronism remained relatively healthy. Thus, malignant hypertensive patients had very high levels of both plasma renin and the sodium-retaining hormone, aldosterone, whereas those with primary aldosteronism had very high aldosterone levels but very low plasma renin levels. 1,2 Thus, in more modern terms,5,20 malignant hypertension had both R and V hypertension, while primary aldosteronism had pure V hypertension with suppressed PRA. The inter-relationships between body sodium content and PRA were examined in 1970 when Bull et al. 21 separately manipulated body sodium content as well as plasma and red blood cell volumes in six normal volunteers, who first underwent dietary and diuretic induced sodium-volume depletion during which PRA and aldosterone levels rose in parallel. Then during dietary sodium repletion, PRA and aldosterone levels fell in parallel as urinary sodium excretion increased even though blood volume was held at low levels by daily plasmapheresis. These findings indicate that expansion or contraction of the extracellular space is a more important determinant of sodium conservation or natriuresis than is the plasma or blood volume. In this model, body sodium-volume content exists in the extracellular fluids and is created by retained sodium chloride ions which hold enough water in the body to ensure that the ECF is isotonic. The links between body sodium content and PRA were again revealed when urinary aldosterone excretion and PRA levels were measured in normal subjects (Figure 2) and in hypertensive patients during wide ranges of sodium intake and related to the 24-h urinary sodium excretion.22,23 Relationship of the 24-h urine sodium excretion (a reflection of the daily sodium intake) to the ambulatory plasma renin activity (PRA) level and to the 24-h urinary aldosterone excretion values in normal subjects (from Laragh et al.99). Because there were only three ambulatory PRA levels Source: https://academic.oup.com/ajh/article/24/11/1164/2281914 Renin Renin Renin is a protein (enzyme) released by special kidney cells when you have decreased salt (sodium levels) or low blood volume. Renin increases the amount of angiotensinogen in the blood, which eventually increases blood pressure. It increases the release of aldosterone, a hormone that helps control the body's salt and water balance. This article discusses the test to measure the activity of renin in your blood. Alternative Names Alternative Names Plasma renin activity; Random plasma renin; PRA How the test is performed How the test is performed A blood sample is needed. For information on how this is done, see: Venipuncture How to prepare for the test How to prepare for the test Your health care provider may tell you to temporarily stop taking certain drugs that can affect test results. Drugs that can affect renin measurements include: Birth control pills Blood pressure medications Diuretics Vasodilators (drugs that enlarge blood vessels; they are usually used to treat high blood pressure or congestive heart failure) You should eat a normal, balanced diet with moderate sodium content (about 3 gm/day) for 3 days before the test. How the test will feel How the test will feel When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing. Why the test is performed Why the test is performed This test is done as part of the diagnosis and treatment of high blood pressure. If you have essential hypertension, your doctor may order a renin and aldosterone test to see if you are sensitive to salt (which causes low renin with normal aldosterone levels). The test results may help to guide your doctor in choosing the correct medication. Salt-sensitive patients with high blood pressure associated with low renin levels respond well to diuretic medications. Normal Values Normal Values Normal values range from 0.2 to 3.3 ng/mL/hour. The examples above are common measurements for results of these tests. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your doctor about the meaning of your specific test results. What abnormal results mean What abnormal results mean High levels of renin may be due to: Addison's disease Cirrhosis Congestive heart failure Dehydration Hemorrhage (bleeding) High blood pressure Hypokalemia Malignant hypertension Nephrotic syndrome Renin-producing renal tumors Renovascular hypertension Low renin levels may be due to: ADH therapy Hyperaldosteronism Sodium-retaining steroid therapy High blood pressure that is sodium-sensitive What the risks are What the risks are Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others. Other risks associated with having blood drawn are slight but may include: Excessive bleeding Fainting or feeling lightheaded Hematoma (blood accumulating under the skin) Infection (a slight risk any time the skin is broken) Special considerations Special considerations Renin measurements are affected by salt intake, pregnancy, time of day, and body position. References Plasma Renin Test Reveals the Contribution of Body Sodium-Volume Content (V) and Renin–Angiotensin (R) Vasoconstriction to Long-Term Blood Pressure Body sodium works together with the plasma renin–angiotensin system to ensure adequate blood flow to the tissues. Body sodium content determines the extracellular fluid (ECF) volume ensuring that, with each heart beat, a sufficient volume of fluid is delivered into the arterial space. At the same time the kidneys monitor ECF volume and blood pressure (BP), so that the juxtaglomerular cells can adjust their net secretion rate of renin to maintain an appropriate plasma renin activity (PRA) level. Plasma renin produces angiotensin II (Ang II) to constrict the arterioles and thereby ensure sufficient BP to deliver an appropriate rate of flow for cardiovascular homeostasis. The low renin, sodium-volume dependent (V) form of essential hypertension occurs whenever body sodium content increases beyond the point where plasma renin–angiotensin vasoconstrictor activity is turned off. In contrast, medium to high renin (R) hypertension occurs when too much renin is secreted relative to the body sodium content. Thus, BP = V × R. This volume-vasoconstriction dual support of long-term hypertension is validated by the fact that all effective long-term antihypertensive drug types are either (i) natriuretic to reduce body salt and volume content (anti-V), or (ii) antirenin to reduce or block the activity of the circulating renin–angiotensin system (anti-R). The PRA test defines the relative participation of the concurrent volume and vasoconstrictor factors. In the hypertensive patient PRA testing can guide initiation, addition or subtraction of anti-V or anti-R antihypertensive drug types to thereby improve BP control and prognosis while reducing drug type usage and cost. American Journal of Hypertension, advance online publication 22 September 2011; doi:10.1038/ajh.2011.171 angiotensin, blood pressure, hypertension, plasma renin activity, plasma renin test, PRA, renin, salt, sodium, vasoconstriction, volume Dietary salt is often portrayed as a killer that causes high blood pressure (BP). At the same time renin is often portrayed as a villain that causes heart attacks, heart failure, renal failure, and strokes. To combat these problems salt is removed from diets, and diuretics and renin–angiotensin system blocking drugs are given. But these approaches ignore the fact that the body salt and the circulating renin–angiotensin system play pivotal roles in determining the level of BP, to sustain an appropriate flow of blood to the tissues and thereby ensure the delivery of nutrients and the removal of metabolic products (Figure 1). In this review, we describe how the plasma renin activity (PRA) test can be used to define the relative involvement of sodium-volume (V) and renin–angiotensin-vasoconstrictor (R) factors in determining BP, making it possible to identify whether a natriuretic anti-V or an antirenin–angiotensin anti-R drug is the correct drug type to effectively and efficiently treat the hypertension of the individual patient. The interacting relationship between body sodium and the circulating renin–angiotensin system to maintain blood pressure, tissue blood flow, and tissue health. ACEI, angiotensin-converting enzyme inhibitor; Ang I, angiotensin I; ARB, angiotensin receptor blocker; BP, blood pressure; DRI, direct renin inhibitor; R, vasoconstrictor activity of the circulating renin–angiotensin system; V, body sodium-volume content Open in new tabDownload slide Physiology and Pathophysiology of the Renin–Angiotensin System The physiological basis for the dual volume-vasoconstriction conception of BP control emerged from many years of clinical research. 1–4 It postulates that long-term BP–as opposed to minute to minute changes in BP–is sustained by two interacting forces: (i) the body sodium-volume content (V) and (ii) the plasma renin–angiotensin (R) vasoconstrictor activity. This V and R interacting control system sustains all normotension, as well as all forms of hypertension–regardless of initiating cause. This twin control of BP is in keeping with the long held view that arterial BP is sensitive to changes in body salt. It also recognizes that body salt does not affect BP directly but does so only by increasing or decreasing the extracellular fluid volume (ECF) and thus (assuming normal cardiac function) the volume of fluid delivered to the arterial tree. This, per se affects arterial BP via an hydraulic effect. In addition, compensatory adjustments in arteriolar caliber are mediated by companion changes in circulating angiotensin II (Ang II). This adjustment occurs whenever the cells of the renal juxtaglomerular apparatus of each nephron detect increases or decreases in body sodium-volume content and then alter their secretion of renin–downward or upward. The vasoconstrictor effects of the induced changes in plasma Ang II, generated by PRA, alter the caliber of the arterioles thereby ensuring that BP is not significantly affected by changes in arterial sodium-volume. Thus, changes in body salt content are buffered by reciprocal changes in PRA to maintain BP homeostasis. In the simplest of terms, arterial BP control can be viewed from the perspective of the 1828 Poiseuille equation: BP = cardiac output × peripheral resistance. In this equation the body sodium-volume content and PRA become functional surrogates for cardiac output and arteriolar resistance respectively: Thus, BP = (sodium-volume) × (PRA), or BP = V × R. In this model, irrespective of the particular BP level, the degree of vasoconstriction caused by the circulating renin–angiotensin system is always proportional to the concurrent PRA level. Thus, a normal BP level can be associated with low, medium or high PRA levels when it is concurrently associated with reciprocally high, medium or low levels of body sodium volume content respectively. From another perspective, the PRA level can be viewed as an index of whether the subject is salt depleted and hypovolemic, or instead is hypervolemic from a salt excess. A high PRA level in a normotensive individual indicates some degree of body sodium-volume depletion, whereas a low PRA level indicates that body sodium-volume status is on the high side. Long-term hypertension (as opposed to acute fluctuations in BP) occurs whenever the kidneys fail to induce a sufficient fall in PRA in response to an increase in body salt. Hypertension may occur because renin secretion is already maximally suppressed, or because there is a defect in juxtaglomerular apparatus sensing mechanisms of individual nephrons that allows too much renin to be secreted for the level of body salt, or because there is overactivity of the sympathetic drive to renin release. Whatever the reason, for hypertension to develop, PRA levels need not be higher than normal–just too high for the concurrent body sodium-volume content. This is why many hypertensive patients with renin-dependent hypertension exhibit PRA levels within the normal range. Moreover, the reciprocals are also true. Whenever BP is successfully controlled, angiotensin-mediated vasoconstriction returns toward the medium range, indicating the return to an appropriate relationship to the body sodium-volume content to achieve optimal tissue flow. The Anti-V and Anti-R Antihypertensive Drug Types A fundamental verifying corollary of this volume-vasoconstriction dual servo-control system for long-term BP regulation is the fact that all effective antihypertensive drugs lower BP by either (i) reducing the body sodium-volume content or (ii) by reducing or blocking the vasoconstrictor activity of the circulating renin–angiotensin system. 5 This fits the underlying pathophysiology because all effective long-term antihypertensive drugs also fall into one of two categories: they are either (i) natriuretic agents that reduce body sodium-volume content–the anti-V drug types (i.e. , sulfonamide diuretics, aldosterone receptor blockers, α-adrenergic blockers,6 calcium channel blockers7–9) or (ii) instead they reduce or block the vasoconstrictor activity of the circulating renin–angiotensin system–these are the antirenin system anti-R drugs (i.e., β-blockers, centrally acting agents (e.g. , clonidine, guanfacine, reserpine), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), direct renin inhibitors (e.g., aliskiren)). The classification of all available antihypertensive drugs into only two functional categories greatly simplifies drug treatment selection strategies because an enormous array of commercially available pharmaceutical agents (Table 1) and combinations thereof can be reduced to only two broad categories, either the natriuretic anti-V or the anti-R drugs (Table 2). This has enabled the development of relatively simple plasma renin-guided algorithms for the treatment of hypertension (discussed below). How does the health care professional choose among the ten classes and 66 or more individual antihypertensive drugs? The anti-V and anti-R categories of antihypertensive drugs Studies That Led To the Volume-Vasoconstriction Analytical Model For Long-Term BP Control These studies were grounded in Poisseuille's formula: (BP = cardiac output × peripheral resistance), in Tigerstedt's discovery of renin,10 in Goldblatt's renovascular model of hypertension,11 and in Conn's discovery of primary aldosteronism. 12 They matured as the biochemical components of the renin–angiotensin system were discovered,13 the sensing mechanisms of the renal juxtaglomerular apparatus were identified,14,15 and at a time when Guyton was identifying the over-riding dominance of the kidneys for sustaining hypertension.16 Body sodium content, PRA, and their interactive relationship to BP The existence of two pathophysiological types of long-term hypertension became apparent during studies of malignant hypertension and of primary aldosteronism that led to our discovery of the link between the circulating renin–angiotensin system and adrenal cortical aldosterone secretion. 17–19 It became clear that these two clinical forms of hypertension were quite different; malignant hypertensive patients were very sick and died within a year whereas those with primary aldosteronism remained relatively healthy. Thus, malignant hypertensive patients had very high levels of both plasma renin and the sodium-retaining hormone, aldosterone, whereas those with primary aldosteronism had very high aldosterone levels but very low plasma renin levels. 1,2 Thus, in more modern terms,5,20 malignant hypertension had both R and V hypertension, while primary aldosteronism had pure V hypertension with suppressed PRA. The inter-relationships between body sodium content and PRA were examined in 1970 when Bull et al. 21 separately manipulated body sodium content as well as plasma and red blood cell volumes in six normal volunteers, who first underwent dietary and diuretic induced sodium-volume depletion during which PRA and aldosterone levels rose in parallel. Then during dietary sodium repletion, PRA and aldosterone levels fell in parallel as urinary sodium excretion increased even though blood volume was held at low levels by daily plasmapheresis. These findings indicate that expansion or contraction of the extracellular space is a more important determinant of sodium conservation or natriuresis than is the plasma or blood volume. In this model, body sodium-volume content exists in the extracellular fluids and is created by retained sodium chloride ions which hold enough water in the body to ensure that the ECF is isotonic. The links between body sodium content and PRA were again revealed when urinary aldosterone excretion and PRA levels were measured in normal subjects (Figure 2) and in hypertensive patients during wide ranges of sodium intake and related to the 24-h urinary sodium excretion.22,23 Relationship of the 24-h urine sodium excretion (a reflection of the daily sodium intake) to the ambulatory plasma renin activity (PRA) level and to the 24-h urinary aldosterone excretion values in normal subjects (from Laragh et al.99). Because there were only three ambulatory PRA levels Source: https://academic.oup.com/ajh/article/24/11/1164/2281914 Renin Renin is a protein (enzyme) released by special kidney cells when you have decreased salt (sodium levels) or low blood volume. Renin increases the amount of angiotensinogen in the blood, which eventually increases blood pressure. It increases the release of aldosterone, a hormone that helps control the body's salt and water balance. This article discusses the test to measure the activity of renin in your blood. Alternative Names Plasma renin activity; Random plasma renin; PRA How the test is performed A blood sample is needed. For information on how this is done, see: Venipuncture How to prepare for the test Your health care provider may tell you to temporarily stop taking certain drugs that can affect test results. Drugs that can affect renin measurements include: Birth control pills Blood pressure medications Diuretics Vasodilators (drugs that enlarge blood vessels; they are usually used to treat high blood pressure or congestive heart failure) You should eat a normal, balanced diet with moderate sodium content (about 3 gm/day) for 3 days before the test. How the test will feel When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing. Why the test is performed This test is done as part of the diagnosis and treatment of high blood pressure. If you have essential hypertension, your doctor may order a renin and aldosterone test to see if you are sensitive to salt (which causes low renin with normal aldosterone levels). The test results may help to guide your doctor in choosing the correct medication. Salt-sensitive patients with high blood pressure associated with low renin levels respond well to diuretic medications. Normal Values Normal values range from 0.2 to 3.3 ng/mL/hour. The examples above are common measurements for results of these tests. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your doctor about the meaning of your specific test results. What abnormal results mean High levels of renin may be due to: Addison's disease Cirrhosis Congestive heart failure Dehydration Hemorrhage (bleeding) High blood pressure Hypokalemia Malignant hypertension Nephrotic syndrome Renin-producing renal tumors Renovascular hypertension Low renin levels may be due to: ADH therapy Hyperaldosteronism Sodium-retaining steroid therapy High blood pressure that is sodium-sensitive What the risks are Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others. Other risks associated with having blood drawn are slight but may include: Excessive bleeding Fainting or feeling lightheaded Hematoma (blood accumulating under the skin) Infection (a slight risk any time the skin is broken) Special considerations Renin measurements are affected by salt intake, pregnancy, time of day, and body position. References Victor RG. Arterial hypertension. In: Goldman L, Schafer AI, eds. Cecil Medicine. 24th ed. Philadelphia, Pa: Saunders Elsevier; 2011:chap 67. Blumenfeld JD, Liu F, Laragh JR. Primary and secondary hypertension. In: Taal MW, Chertow GM, Marsden PA, Skorecki K, Yu ASL, Brenner BM, eds. Brenner & Rector's The Kidney. 9th ed. Philadelphia, PA: Saunders Elsevier; 2011:chap 46. Review Date: 9/3/2012 The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed physician should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only — they do not constitute endorsements of those other sites. Copyright ©2003 A.D.A.M., Inc., as modified by University of California San Francisco. Any duplication or distribution of the information contained herein is strictly prohibited. Information developed by A.D.A.M., Inc. regarding tests and test results may not directly correspond with information provided by UCSF Medical Center. Please discuss with your doctor any questions or concerns you may have. Source: https://www.ucsfbenioffchildrens.org/tests/003698.html
  50. Renin
  51. Alternative Names
  52. How the test is performed
  53. How to prepare for the test
  54. How the test will feel
  55. Why the test is performed
  56. Normal Values
  57. What abnormal results mean
  58. What the risks are
  59. Special considerations
  60. Plasma Renin Test Reveals the Contribution of Body Sodium-Volume Content (V) and Renin–Angiotensin (R) Vasoconstriction to Long-Term Blood Pressure
  61. The interacting relationship between body sodium and the circulating renin–angiotensin system to maintain blood pressure, tissue blood flow, and tissue health. ACEI, angiotensin-converting enzyme inhibitor; Ang I, angiotensin I; ARB, angiotensin receptor blocker; BP, blood pressure; DRI, direct renin inhibitor; R, vasoconstrictor activity of the circulating renin–angiotensin system; V, body sodium-volume content
  62. Physiology and Pathophysiology of the Renin–Angiotensin System
  63. The Anti-V and Anti-R Antihypertensive Drug Types
  64. Studies That Led To the Volume-Vasoconstriction Analytical Model For Long-Term BP Control
  65. Body sodium content, PRA, and their interactive relationship to BP
  66. Relationship of the 24-h urine sodium excretion (a reflection of the daily sodium intake) to the ambulatory plasma renin activity (PRA) level and to the 24-h urinary aldosterone excretion values in normal subjects (from Laragh et al.99). Because there were only three ambulatory PRA levels Source: https://academic.oup.com/ajh/article/24/11/1164/2281914 Renin Renin Renin is a protein (enzyme) released by special kidney cells when you have decreased salt (sodium levels) or low blood volume. Renin increases the amount of angiotensinogen in the blood, which eventually increases blood pressure. It increases the release of aldosterone, a hormone that helps control the body's salt and water balance. This article discusses the test to measure the activity of renin in your blood. Alternative Names Alternative Names Plasma renin activity; Random plasma renin; PRA How the test is performed How the test is performed A blood sample is needed. For information on how this is done, see: Venipuncture How to prepare for the test How to prepare for the test Your health care provider may tell you to temporarily stop taking certain drugs that can affect test results. Drugs that can affect renin measurements include: Birth control pills Blood pressure medications Diuretics Vasodilators (drugs that enlarge blood vessels; they are usually used to treat high blood pressure or congestive heart failure) You should eat a normal, balanced diet with moderate sodium content (about 3 gm/day) for 3 days before the test. How the test will feel How the test will feel When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing. Why the test is performed Why the test is performed This test is done as part of the diagnosis and treatment of high blood pressure. If you have essential hypertension, your doctor may order a renin and aldosterone test to see if you are sensitive to salt (which causes low renin with normal aldosterone levels). The test results may help to guide your doctor in choosing the correct medication. Salt-sensitive patients with high blood pressure associated with low renin levels respond well to diuretic medications. Normal Values Normal Values Normal values range from 0.2 to 3.3 ng/mL/hour. The examples above are common measurements for results of these tests. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your doctor about the meaning of your specific test results. What abnormal results mean What abnormal results mean High levels of renin may be due to: Addison's disease Cirrhosis Congestive heart failure Dehydration Hemorrhage (bleeding) High blood pressure Hypokalemia Malignant hypertension Nephrotic syndrome Renin-producing renal tumors Renovascular hypertension Low renin levels may be due to: ADH therapy Hyperaldosteronism Sodium-retaining steroid therapy High blood pressure that is sodium-sensitive What the risks are What the risks are Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others. Other risks associated with having blood drawn are slight but may include: Excessive bleeding Fainting or feeling lightheaded Hematoma (blood accumulating under the skin) Infection (a slight risk any time the skin is broken) Special considerations Special considerations Renin measurements are affected by salt intake, pregnancy, time of day, and body position. References Plasma Renin Test Reveals the Contribution of Body Sodium-Volume Content (V) and Renin–Angiotensin (R) Vasoconstriction to Long-Term Blood Pressure Body sodium works together with the plasma renin–angiotensin system to ensure adequate blood flow to the tissues. Body sodium content determines the extracellular fluid (ECF) volume ensuring that, with each heart beat, a sufficient volume of fluid is delivered into the arterial space. At the same time the kidneys monitor ECF volume and blood pressure (BP), so that the juxtaglomerular cells can adjust their net secretion rate of renin to maintain an appropriate plasma renin activity (PRA) level. Plasma renin produces angiotensin II (Ang II) to constrict the arterioles and thereby ensure sufficient BP to deliver an appropriate rate of flow for cardiovascular homeostasis. The low renin, sodium-volume dependent (V) form of essential hypertension occurs whenever body sodium content increases beyond the point where plasma renin–angiotensin vasoconstrictor activity is turned off. In contrast, medium to high renin (R) hypertension occurs when too much renin is secreted relative to the body sodium content. Thus, BP = V × R. This volume-vasoconstriction dual support of long-term hypertension is validated by the fact that all effective long-term antihypertensive drug types are either (i) natriuretic to reduce body salt and volume content (anti-V), or (ii) antirenin to reduce or block the activity of the circulating renin–angiotensin system (anti-R). The PRA test defines the relative participation of the concurrent volume and vasoconstrictor factors. In the hypertensive patient PRA testing can guide initiation, addition or subtraction of anti-V or anti-R antihypertensive drug types to thereby improve BP control and prognosis while reducing drug type usage and cost. American Journal of Hypertension, advance online publication 22 September 2011; doi:10.1038/ajh.2011.171 angiotensin, blood pressure, hypertension, plasma renin activity, plasma renin test, PRA, renin, salt, sodium, vasoconstriction, volume Dietary salt is often portrayed as a killer that causes high blood pressure (BP). At the same time renin is often portrayed as a villain that causes heart attacks, heart failure, renal failure, and strokes. To combat these problems salt is removed from diets, and diuretics and renin–angiotensin system blocking drugs are given. But these approaches ignore the fact that the body salt and the circulating renin–angiotensin system play pivotal roles in determining the level of BP, to sustain an appropriate flow of blood to the tissues and thereby ensure the delivery of nutrients and the removal of metabolic products (Figure 1). In this review, we describe how the plasma renin activity (PRA) test can be used to define the relative involvement of sodium-volume (V) and renin–angiotensin-vasoconstrictor (R) factors in determining BP, making it possible to identify whether a natriuretic anti-V or an antirenin–angiotensin anti-R drug is the correct drug type to effectively and efficiently treat the hypertension of the individual patient. The interacting relationship between body sodium and the circulating renin–angiotensin system to maintain blood pressure, tissue blood flow, and tissue health. ACEI, angiotensin-converting enzyme inhibitor; Ang I, angiotensin I; ARB, angiotensin receptor blocker; BP, blood pressure; DRI, direct renin inhibitor; R, vasoconstrictor activity of the circulating renin–angiotensin system; V, body sodium-volume content Open in new tabDownload slide Physiology and Pathophysiology of the Renin–Angiotensin System The physiological basis for the dual volume-vasoconstriction conception of BP control emerged from many years of clinical research. 1–4 It postulates that long-term BP–as opposed to minute to minute changes in BP–is sustained by two interacting forces: (i) the body sodium-volume content (V) and (ii) the plasma renin–angiotensin (R) vasoconstrictor activity. This V and R interacting control system sustains all normotension, as well as all forms of hypertension–regardless of initiating cause. This twin control of BP is in keeping with the long held view that arterial BP is sensitive to changes in body salt. It also recognizes that body salt does not affect BP directly but does so only by increasing or decreasing the extracellular fluid volume (ECF) and thus (assuming normal cardiac function) the volume of fluid delivered to the arterial tree. This, per se affects arterial BP via an hydraulic effect. In addition, compensatory adjustments in arteriolar caliber are mediated by companion changes in circulating angiotensin II (Ang II). This adjustment occurs whenever the cells of the renal juxtaglomerular apparatus of each nephron detect increases or decreases in body sodium-volume content and then alter their secretion of renin–downward or upward. The vasoconstrictor effects of the induced changes in plasma Ang II, generated by PRA, alter the caliber of the arterioles thereby ensuring that BP is not significantly affected by changes in arterial sodium-volume. Thus, changes in body salt content are buffered by reciprocal changes in PRA to maintain BP homeostasis. In the simplest of terms, arterial BP control can be viewed from the perspective of the 1828 Poiseuille equation: BP = cardiac output × peripheral resistance. In this equation the body sodium-volume content and PRA become functional surrogates for cardiac output and arteriolar resistance respectively: Thus, BP = (sodium-volume) × (PRA), or BP = V × R. In this model, irrespective of the particular BP level, the degree of vasoconstriction caused by the circulating renin–angiotensin system is always proportional to the concurrent PRA level. Thus, a normal BP level can be associated with low, medium or high PRA levels when it is concurrently associated with reciprocally high, medium or low levels of body sodium volume content respectively. From another perspective, the PRA level can be viewed as an index of whether the subject is salt depleted and hypovolemic, or instead is hypervolemic from a salt excess. A high PRA level in a normotensive individual indicates some degree of body sodium-volume depletion, whereas a low PRA level indicates that body sodium-volume status is on the high side. Long-term hypertension (as opposed to acute fluctuations in BP) occurs whenever the kidneys fail to induce a sufficient fall in PRA in response to an increase in body salt. Hypertension may occur because renin secretion is already maximally suppressed, or because there is a defect in juxtaglomerular apparatus sensing mechanisms of individual nephrons that allows too much renin to be secreted for the level of body salt, or because there is overactivity of the sympathetic drive to renin release. Whatever the reason, for hypertension to develop, PRA levels need not be higher than normal–just too high for the concurrent body sodium-volume content. This is why many hypertensive patients with renin-dependent hypertension exhibit PRA levels within the normal range. Moreover, the reciprocals are also true. Whenever BP is successfully controlled, angiotensin-mediated vasoconstriction returns toward the medium range, indicating the return to an appropriate relationship to the body sodium-volume content to achieve optimal tissue flow. The Anti-V and Anti-R Antihypertensive Drug Types A fundamental verifying corollary of this volume-vasoconstriction dual servo-control system for long-term BP regulation is the fact that all effective antihypertensive drugs lower BP by either (i) reducing the body sodium-volume content or (ii) by reducing or blocking the vasoconstrictor activity of the circulating renin–angiotensin system. 5 This fits the underlying pathophysiology because all effective long-term antihypertensive drugs also fall into one of two categories: they are either (i) natriuretic agents that reduce body sodium-volume content–the anti-V drug types (i.e. , sulfonamide diuretics, aldosterone receptor blockers, α-adrenergic blockers,6 calcium channel blockers7–9) or (ii) instead they reduce or block the vasoconstrictor activity of the circulating renin–angiotensin system–these are the antirenin system anti-R drugs (i.e., β-blockers, centrally acting agents (e.g. , clonidine, guanfacine, reserpine), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), direct renin inhibitors (e.g., aliskiren)). The classification of all available antihypertensive drugs into only two functional categories greatly simplifies drug treatment selection strategies because an enormous array of commercially available pharmaceutical agents (Table 1) and combinations thereof can be reduced to only two broad categories, either the natriuretic anti-V or the anti-R drugs (Table 2). This has enabled the development of relatively simple plasma renin-guided algorithms for the treatment of hypertension (discussed below). How does the health care professional choose among the ten classes and 66 or more individual antihypertensive drugs? The anti-V and anti-R categories of antihypertensive drugs Studies That Led To the Volume-Vasoconstriction Analytical Model For Long-Term BP Control These studies were grounded in Poisseuille's formula: (BP = cardiac output × peripheral resistance), in Tigerstedt's discovery of renin,10 in Goldblatt's renovascular model of hypertension,11 and in Conn's discovery of primary aldosteronism. 12 They matured as the biochemical components of the renin–angiotensin system were discovered,13 the sensing mechanisms of the renal juxtaglomerular apparatus were identified,14,15 and at a time when Guyton was identifying the over-riding dominance of the kidneys for sustaining hypertension.16 Body sodium content, PRA, and their interactive relationship to BP The existence of two pathophysiological types of long-term hypertension became apparent during studies of malignant hypertension and of primary aldosteronism that led to our discovery of the link between the circulating renin–angiotensin system and adrenal cortical aldosterone secretion. 17–19 It became clear that these two clinical forms of hypertension were quite different; malignant hypertensive patients were very sick and died within a year whereas those with primary aldosteronism remained relatively healthy. Thus, malignant hypertensive patients had very high levels of both plasma renin and the sodium-retaining hormone, aldosterone, whereas those with primary aldosteronism had very high aldosterone levels but very low plasma renin levels. 1,2 Thus, in more modern terms,5,20 malignant hypertension had both R and V hypertension, while primary aldosteronism had pure V hypertension with suppressed PRA. The inter-relationships between body sodium content and PRA were examined in 1970 when Bull et al. 21 separately manipulated body sodium content as well as plasma and red blood cell volumes in six normal volunteers, who first underwent dietary and diuretic induced sodium-volume depletion during which PRA and aldosterone levels rose in parallel. Then during dietary sodium repletion, PRA and aldosterone levels fell in parallel as urinary sodium excretion increased even though blood volume was held at low levels by daily plasmapheresis. These findings indicate that expansion or contraction of the extracellular space is a more important determinant of sodium conservation or natriuresis than is the plasma or blood volume. In this model, body sodium-volume content exists in the extracellular fluids and is created by retained sodium chloride ions which hold enough water in the body to ensure that the ECF is isotonic. The links between body sodium content and PRA were again revealed when urinary aldosterone excretion and PRA levels were measured in normal subjects (Figure 2) and in hypertensive patients during wide ranges of sodium intake and related to the 24-h urinary sodium excretion.22,23 Relationship of the 24-h urine sodium excretion (a reflection of the daily sodium intake) to the ambulatory plasma renin activity (PRA) level and to the 24-h urinary aldosterone excretion values in normal subjects (from Laragh et al.99). Because there were only three ambulatory PRA levels Source: https://academic.oup.com/ajh/article/24/11/1164/2281914 Renin Renin is a protein (enzyme) released by special kidney cells when you have decreased salt (sodium levels) or low blood volume. Renin increases the amount of angiotensinogen in the blood, which eventually increases blood pressure. It increases the release of aldosterone, a hormone that helps control the body's salt and water balance. This article discusses the test to measure the activity of renin in your blood. Alternative Names Plasma renin activity; Random plasma renin; PRA How the test is performed A blood sample is needed. For information on how this is done, see: Venipuncture How to prepare for the test Your health care provider may tell you to temporarily stop taking certain drugs that can affect test results. Drugs that can affect renin measurements include: Birth control pills Blood pressure medications Diuretics Vasodilators (drugs that enlarge blood vessels; they are usually used to treat high blood pressure or congestive heart failure) You should eat a normal, balanced diet with moderate sodium content (about 3 gm/day) for 3 days before the test. How the test will feel When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing. Why the test is performed This test is done as part of the diagnosis and treatment of high blood pressure. If you have essential hypertension, your doctor may order a renin and aldosterone test to see if you are sensitive to salt (which causes low renin with normal aldosterone levels). The test results may help to guide your doctor in choosing the correct medication. Salt-sensitive patients with high blood pressure associated with low renin levels respond well to diuretic medications. Normal Values Normal values range from 0.2 to 3.3 ng/mL/hour. The examples above are common measurements for results of these tests. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your doctor about the meaning of your specific test results. What abnormal results mean High levels of renin may be due to: Addison's disease Cirrhosis Congestive heart failure Dehydration Hemorrhage (bleeding) High blood pressure Hypokalemia Malignant hypertension Nephrotic syndrome Renin-producing renal tumors Renovascular hypertension Low renin levels may be due to: ADH therapy Hyperaldosteronism Sodium-retaining steroid therapy High blood pressure that is sodium-sensitive What the risks are Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others. Other risks associated with having blood drawn are slight but may include: Excessive bleeding Fainting or feeling lightheaded Hematoma (blood accumulating under the skin) Infection (a slight risk any time the skin is broken) Special considerations Renin measurements are affected by salt intake, pregnancy, time of day, and body position. References Victor RG. Arterial hypertension. In: Goldman L, Schafer AI, eds. Cecil Medicine. 24th ed. Philadelphia, Pa: Saunders Elsevier; 2011:chap 67. Blumenfeld JD, Liu F, Laragh JR. Primary and secondary hypertension. In: Taal MW, Chertow GM, Marsden PA, Skorecki K, Yu ASL, Brenner BM, eds. Brenner & Rector's The Kidney. 9th ed. Philadelphia, PA: Saunders Elsevier; 2011:chap 46. Review Date: 9/3/2012 The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed physician should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only — they do not constitute endorsements of those other sites. Copyright ©2003 A.D.A.M., Inc., as modified by University of California San Francisco. Any duplication or distribution of the information contained herein is strictly prohibited. Information developed by A.D.A.M., Inc. regarding tests and test results may not directly correspond with information provided by UCSF Medical Center. Please discuss with your doctor any questions or concerns you may have. Source: https://www.ucsfbenioffchildrens.org/tests/003698.html
  67. Renin
  68. Renin
  69. Alternative Names
  70. Alternative Names
  71. How the test is performed
  72. How the test is performed
  73. How to prepare for the test
  74. How to prepare for the test
  75. How the test will feel
  76. How the test will feel
  77. Why the test is performed
  78. Why the test is performed
  79. Normal Values
  80. Normal Values
  81. What abnormal results mean
  82. What abnormal results mean
  83. What the risks are
  84. What the risks are
  85. Special considerations
  86. Special considerations
  87. References
  88. Plasma Renin Test Reveals the Contribution of Body Sodium-Volume Content (V) and Renin–Angiotensin (R) Vasoconstriction to Long-Term Blood Pressure
  89. The interacting relationship between body sodium and the circulating renin–angiotensin system to maintain blood pressure, tissue blood flow, and tissue health. ACEI, angiotensin-converting enzyme inhibitor; Ang I, angiotensin I; ARB, angiotensin receptor blocker; BP, blood pressure; DRI, direct renin inhibitor; R, vasoconstrictor activity of the circulating renin–angiotensin system; V, body sodium-volume content
  90. Physiology and Pathophysiology of the Renin–Angiotensin System
  91. The Anti-V and Anti-R Antihypertensive Drug Types
  92. Studies That Led To the Volume-Vasoconstriction Analytical Model For Long-Term BP Control
  93. Body sodium content, PRA, and their interactive relationship to BP
  94. Relationship of the 24-h urine sodium excretion (a reflection of the daily sodium intake) to the ambulatory plasma renin activity (PRA) level and to the 24-h urinary aldosterone excretion values in normal subjects (from Laragh et al.99). Because there were only three ambulatory PRA levels Source: https://academic.oup.com/ajh/article/24/11/1164/2281914 Renin Renin is a protein (enzyme) released by special kidney cells when you have decreased salt (sodium levels) or low blood volume. Renin increases the amount of angiotensinogen in the blood, which eventually increases blood pressure. It increases the release of aldosterone, a hormone that helps control the body's salt and water balance. This article discusses the test to measure the activity of renin in your blood. Alternative Names Plasma renin activity; Random plasma renin; PRA How the test is performed A blood sample is needed. For information on how this is done, see: Venipuncture How to prepare for the test Your health care provider may tell you to temporarily stop taking certain drugs that can affect test results. Drugs that can affect renin measurements include: Birth control pills Blood pressure medications Diuretics Vasodilators (drugs that enlarge blood vessels; they are usually used to treat high blood pressure or congestive heart failure) You should eat a normal, balanced diet with moderate sodium content (about 3 gm/day) for 3 days before the test. How the test will feel When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing. Why the test is performed This test is done as part of the diagnosis and treatment of high blood pressure. If you have essential hypertension, your doctor may order a renin and aldosterone test to see if you are sensitive to salt (which causes low renin with normal aldosterone levels). The test results may help to guide your doctor in choosing the correct medication. Salt-sensitive patients with high blood pressure associated with low renin levels respond well to diuretic medications. Normal Values Normal values range from 0.2 to 3.3 ng/mL/hour. The examples above are common measurements for results of these tests. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your doctor about the meaning of your specific test results. What abnormal results mean High levels of renin may be due to: Addison's disease Cirrhosis Congestive heart failure Dehydration Hemorrhage (bleeding) High blood pressure Hypokalemia Malignant hypertension Nephrotic syndrome Renin-producing renal tumors Renovascular hypertension Low renin levels may be due to: ADH therapy Hyperaldosteronism Sodium-retaining steroid therapy High blood pressure that is sodium-sensitive What the risks are Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others. Other risks associated with having blood drawn are slight but may include: Excessive bleeding Fainting or feeling lightheaded Hematoma (blood accumulating under the skin) Infection (a slight risk any time the skin is broken) Special considerations Renin measurements are affected by salt intake, pregnancy, time of day, and body position. References Victor RG. Arterial hypertension. In: Goldman L, Schafer AI, eds. Cecil Medicine. 24th ed. Philadelphia, Pa: Saunders Elsevier; 2011:chap 67. Blumenfeld JD, Liu F, Laragh JR. Primary and secondary hypertension. In: Taal MW, Chertow GM, Marsden PA, Skorecki K, Yu ASL, Brenner BM, eds. Brenner & Rector's The Kidney. 9th ed. Philadelphia, PA: Saunders Elsevier; 2011:chap 46. Review Date: 9/3/2012 The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed physician should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only — they do not constitute endorsements of those other sites. Copyright ©2003 A.D.A.M., Inc., as modified by University of California San Francisco. Any duplication or distribution of the information contained herein is strictly prohibited. Information developed by A.D.A.M., Inc. regarding tests and test results may not directly correspond with information provided by UCSF Medical Center. Please discuss with your doctor any questions or concerns you may have. Source: https://www.ucsfbenioffchildrens.org/tests/003698.html
  95. Renin
  96. Alternative Names
  97. How the test is performed
  98. How to prepare for the test
  99. How the test will feel
  100. Why the test is performed
  101. Normal Values
  102. What abnormal results mean
  103. What the risks are
  104. Special considerations
  105. References

Plasma Renin Test Reveals the Contribution of Body Sodium-Volume Content (V) and Renin–Angiotensin (R) Vasoconstriction to Long-Term Blood Pressure

What Is Renin? Blood Test & Low Renin Causes
What Is Renin? Blood Test & Low Renin Causes

Body sodium works together with the plasma renin–angiotensin system to ensure adequate blood flow to the tissues. Body sodium content determines the extracellular fluid (ECF) volume ensuring that, with each heart beat, a sufficient volume of fluid is delivered into the arterial space.

At the same time the kidneys monitor ECF volume and blood pressure (BP), so that the juxtaglomerular cells can adjust their net secretion rate of renin to maintain an appropriate plasma renin activity (PRA) level.

Plasma renin produces angiotensin II (Ang II) to constrict the arterioles and thereby ensure sufficient BP to deliver an appropriate rate of flow for cardiovascular homeostasis.

The low renin, sodium-volume dependent (V) form of essential hypertension occurs whenever body sodium content increases beyond the point where plasma renin–angiotensin vasoconstrictor activity is turned off. In contrast, medium to high renin (R) hypertension occurs when too much renin is secreted relative to the body sodium content.

Thus, BP = V × R.

This volume-vasoconstriction dual support of long-term hypertension is validated by the fact that all effective long-term antihypertensive drug types are either (i) natriuretic to reduce body salt and volume content (anti-V), or (ii) antirenin to reduce or block the activity of the circulating renin–angiotensin system (anti-R). The PRA test defines the relative participation of the concurrent volume and vasoconstrictor factors. In the hypertensive patient PRA testing can guide initiation, addition or subtraction of anti-V or anti-R antihypertensive drug types to thereby improve BP control and prognosis while reducing drug type usage and cost.

American Journal of Hypertension, advance online publication 22 September 2011; doi:10.1038/ajh.2011.171

angiotensin, blood pressure, hypertension, plasma renin activity, plasma renin test, PRA, renin, salt, sodium, vasoconstriction, volume

Dietary salt is often portrayed as a killer that causes high blood pressure (BP). At the same time renin is often portrayed as a villain that causes heart attacks, heart failure, renal failure, and strokes. To combat these problems salt is removed from diets, and diuretics and renin–angiotensin system blocking drugs are given.

But these approaches ignore the fact that the body salt and the circulating renin–angiotensin system play pivotal roles in determining the level of BP, to sustain an appropriate flow of blood to the tissues and thereby ensure the delivery of nutrients and the removal of metabolic products (Figure 1).

In this review, we describe how the plasma renin activity (PRA) test can be used to define the relative involvement of sodium-volume (V) and renin–angiotensin-vasoconstrictor (R) factors in determining BP, making it possible to identify whether a natriuretic anti-V or an antirenin–angiotensin anti-R drug is the correct drug type to effectively and efficiently treat the hypertension of the individual patient.

Physiology and Pathophysiology of the Renin–Angiotensin System

The physiological basis for the dual volume-vasoconstriction conception of BP control emerged from many years of clinical research.

1–4 It postulates that long-term BP–as opposed to minute to minute changes in BP–is sustained by two interacting forces: (i) the body sodium-volume content (V) and (ii) the plasma renin–angiotensin (R) vasoconstrictor activity.

This V and R interacting control system sustains all normotension, as well as all forms of hypertension–regardless of initiating cause.

This twin control of BP is in keeping with the long held view that arterial BP is sensitive to changes in body salt. It also recognizes that body salt does not affect BP directly but does so only by increasing or decreasing the extracellular fluid volume (ECF) and thus (assuming normal cardiac function) the volume of fluid delivered to the arterial tree.

This, per se affects arterial BP via an hydraulic effect. In addition, compensatory adjustments in arteriolar caliber are mediated by companion changes in circulating angiotensin II (Ang II).

This adjustment occurs whenever the cells of the renal juxtaglomerular apparatus of each nephron detect increases or decreases in body sodium-volume content and then alter their secretion of renin–downward or upward.

The vasoconstrictor effects of the induced changes in plasma Ang II, generated by PRA, alter the caliber of the arterioles thereby ensuring that BP is not significantly affected by changes in arterial sodium-volume. Thus, changes in body salt content are buffered by reciprocal changes in PRA to maintain BP homeostasis.

In the simplest of terms, arterial BP control can be viewed from the perspective of the 1828 Poiseuille equation: BP = cardiac output × peripheral resistance. In this equation the body sodium-volume content and PRA become functional surrogates for cardiac output and arteriolar resistance respectively: Thus, BP = (sodium-volume) × (PRA), or BP = V × R.

In this model, irrespective of the particular BP level, the degree of vasoconstriction caused by the circulating renin–angiotensin system is always proportional to the concurrent PRA level.

Thus, a normal BP level can be associated with low, medium or high PRA levels when it is concurrently associated with reciprocally high, medium or low levels of body sodium volume content respectively. From another perspective, the PRA level can be viewed as an index of whether the subject is salt depleted and hypovolemic, or instead is hypervolemic from a salt excess.

A high PRA level in a normotensive individual indicates some degree of body sodium-volume depletion, whereas a low PRA level indicates that body sodium-volume status is on the high side.

Long-term hypertension (as opposed to acute fluctuations in BP) occurs whenever the kidneys fail to induce a sufficient fall in PRA in response to an increase in body salt.

Hypertension may occur because renin secretion is already maximally suppressed, or because there is a defect in juxtaglomerular apparatus sensing mechanisms of individual nephrons that allows too much renin to be secreted for the level of body salt, or because there is overactivity of the sympathetic drive to renin release.

Whatever the reason, for hypertension to develop, PRA levels need not be higher than normal–just too high for the concurrent body sodium-volume content. This is why many hypertensive patients with renin-dependent hypertension exhibit PRA levels within the normal range.

Moreover, the reciprocals are also true. Whenever BP is successfully controlled, angiotensin-mediated vasoconstriction returns toward the medium range, indicating the return to an appropriate relationship to the body sodium-volume content to achieve optimal tissue flow.

The Anti-V and Anti-R Antihypertensive Drug Types

A fundamental verifying corollary of this volume-vasoconstriction dual servo-control system for long-term BP regulation is the fact that all effective antihypertensive drugs lower BP by either (i) reducing the body sodium-volume content or (ii) by reducing or blocking the vasoconstrictor activity of the circulating renin–angiotensin system.

5 This fits the underlying pathophysiology because all effective long-term antihypertensive drugs also fall into one of two categories: they are either (i) natriuretic agents that reduce body sodium-volume content–the anti-V drug types (i.e.

, sulfonamide diuretics, aldosterone receptor blockers, α-adrenergic blockers,6 calcium channel blockers7–9) or (ii) instead they reduce or block the vasoconstrictor activity of the circulating renin–angiotensin system–these are the antirenin system anti-R drugs (i.e., β-blockers, centrally acting agents (e.g.

, clonidine, guanfacine, reserpine), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), direct renin inhibitors (e.g., aliskiren)).

The classification of all available antihypertensive drugs into only two functional categories greatly simplifies drug treatment selection strategies because an enormous array of commercially available pharmaceutical agents (Table 1) and combinations thereof can be reduced to only two broad categories, either the natriuretic anti-V or the anti-R drugs (Table 2). This has enabled the development of relatively simple plasma renin-guided algorithms for the treatment of hypertension (discussed below).

How does the health care professional choose among the ten classes and 66 or more individual antihypertensive drugs?

The anti-V and anti-R categories of antihypertensive drugs

Studies That Led To the Volume-Vasoconstriction Analytical Model For Long-Term BP Control

These studies were grounded in Poisseuille's formula: (BP = cardiac output × peripheral resistance), in Tigerstedt's discovery of renin,10 in Goldblatt's renovascular model of hypertension,11 and in Conn's discovery of primary aldosteronism.

12 They matured as the biochemical components of the renin–angiotensin system were discovered,13 the sensing mechanisms of the renal juxtaglomerular apparatus were identified,14,15 and at a time when Guyton was identifying the over-riding dominance of the kidneys for sustaining hypertension.16

Body sodium content, PRA, and their interactive relationship to BP

The existence of two pathophysiological types of long-term hypertension became apparent during studies of malignant hypertension and of primary aldosteronism that led to our discovery of the link between the circulating renin–angiotensin system and adrenal cortical aldosterone secretion.

17–19 It became clear that these two clinical forms of hypertension were quite different; malignant hypertensive patients were very sick and died within a year whereas those with primary aldosteronism remained relatively healthy.

Thus, malignant hypertensive patients had very high levels of both plasma renin and the sodium-retaining hormone, aldosterone, whereas those with primary aldosteronism had very high aldosterone levels but very low plasma renin levels.

1,2 Thus, in more modern terms,5,20 malignant hypertension had both R and V hypertension, while primary aldosteronism had pure V hypertension with suppressed PRA.

The inter-relationships between body sodium content and PRA were examined in 1970 when Bull et al.

21 separately manipulated body sodium content as well as plasma and red blood cell volumes in six normal volunteers, who first underwent dietary and diuretic induced sodium-volume depletion during which PRA and aldosterone levels rose in parallel.

Then during dietary sodium repletion, PRA and aldosterone levels fell in parallel as urinary sodium excretion increased even though blood volume was held at low levels by daily plasmapheresis.

These findings indicate that expansion or contraction of the extracellular space is a more important determinant of sodium conservation or natriuresis than is the plasma or blood volume. In this model, body sodium-volume content exists in the extracellular fluids and is created by retained sodium chloride ions which hold enough water in the body to ensure that the ECF is isotonic.

The links between body sodium content and PRA were again revealed when urinary aldosterone excretion and PRA levels were measured in normal subjects (Figure 2) and in hypertensive patients during wide ranges of sodium intake and related to the 24-h urinary sodium excretion.22,23

Renin

What Is Renin? Blood Test & Low Renin Causes

Renin

What Is Renin? Blood Test & Low Renin Causes

Renin

What Is Renin? Blood Test & Low Renin Causes

Renin is a protein (enzyme) released by special kidney cells when you have decreased salt (sodium levels) or low blood volume.

Renin increases the amount of angiotensinogen in the blood, which eventually increases blood pressure. It increases the release of aldosterone, a hormone that helps control the body's salt and water balance.

This article discusses the test to measure the activity of renin in your blood.

Alternative Names

Plasma Renin Test Reveals the Contribution of Body Sodium-Volume Content (V) and Renin–Angiotensin (R) Vasoconstriction to Long-Term Blood Pressure

What Is Renin? Blood Test & Low Renin Causes
What Is Renin? Blood Test & Low Renin Causes

Body sodium works together with the plasma renin–angiotensin system to ensure adequate blood flow to the tissues. Body sodium content determines the extracellular fluid (ECF) volume ensuring that, with each heart beat, a sufficient volume of fluid is delivered into the arterial space.

At the same time the kidneys monitor ECF volume and blood pressure (BP), so that the juxtaglomerular cells can adjust their net secretion rate of renin to maintain an appropriate plasma renin activity (PRA) level.

Plasma renin produces angiotensin II (Ang II) to constrict the arterioles and thereby ensure sufficient BP to deliver an appropriate rate of flow for cardiovascular homeostasis.

The low renin, sodium-volume dependent (V) form of essential hypertension occurs whenever body sodium content increases beyond the point where plasma renin–angiotensin vasoconstrictor activity is turned off. In contrast, medium to high renin (R) hypertension occurs when too much renin is secreted relative to the body sodium content.

Thus, BP = V × R.

This volume-vasoconstriction dual support of long-term hypertension is validated by the fact that all effective long-term antihypertensive drug types are either (i) natriuretic to reduce body salt and volume content (anti-V), or (ii) antirenin to reduce or block the activity of the circulating renin–angiotensin system (anti-R). The PRA test defines the relative participation of the concurrent volume and vasoconstrictor factors. In the hypertensive patient PRA testing can guide initiation, addition or subtraction of anti-V or anti-R antihypertensive drug types to thereby improve BP control and prognosis while reducing drug type usage and cost.

American Journal of Hypertension, advance online publication 22 September 2011; doi:10.1038/ajh.2011.171

angiotensin, blood pressure, hypertension, plasma renin activity, plasma renin test, PRA, renin, salt, sodium, vasoconstriction, volume

Dietary salt is often portrayed as a killer that causes high blood pressure (BP). At the same time renin is often portrayed as a villain that causes heart attacks, heart failure, renal failure, and strokes. To combat these problems salt is removed from diets, and diuretics and renin–angiotensin system blocking drugs are given.

But these approaches ignore the fact that the body salt and the circulating renin–angiotensin system play pivotal roles in determining the level of BP, to sustain an appropriate flow of blood to the tissues and thereby ensure the delivery of nutrients and the removal of metabolic products (Figure 1).

In this review, we describe how the plasma renin activity (PRA) test can be used to define the relative involvement of sodium-volume (V) and renin–angiotensin-vasoconstrictor (R) factors in determining BP, making it possible to identify whether a natriuretic anti-V or an antirenin–angiotensin anti-R drug is the correct drug type to effectively and efficiently treat the hypertension of the individual patient.

The interacting relationship between body sodium and the circulating renin–angiotensin system to maintain blood pressure, tissue blood flow, and tissue health. ACEI, angiotensin-converting enzyme inhibitor; Ang I, angiotensin I; ARB, angiotensin receptor blocker; BP, blood pressure; DRI, direct renin inhibitor; R, vasoconstrictor activity of the circulating renin–angiotensin system; V, body sodium-volume content

Renin

What Is Renin? Blood Test & Low Renin Causes

Renin is a protein (enzyme) released by special kidney cells when you have decreased salt (sodium levels) or low blood volume.

Renin increases the amount of angiotensinogen in the blood, which eventually increases blood pressure. It increases the release of aldosterone, a hormone that helps control the body's salt and water balance.

This article discusses the test to measure the activity of renin in your blood.

Alternative Names

Plasma renin activity; Random plasma renin; PRA

How the test is performed

Plasma Renin Test Reveals the Contribution of Body Sodium-Volume Content (V) and Renin–Angiotensin (R) Vasoconstriction to Long-Term Blood Pressure

What Is Renin? Blood Test & Low Renin Causes
What Is Renin? Blood Test & Low Renin Causes

Body sodium works together with the plasma renin–angiotensin system to ensure adequate blood flow to the tissues. Body sodium content determines the extracellular fluid (ECF) volume ensuring that, with each heart beat, a sufficient volume of fluid is delivered into the arterial space.

At the same time the kidneys monitor ECF volume and blood pressure (BP), so that the juxtaglomerular cells can adjust their net secretion rate of renin to maintain an appropriate plasma renin activity (PRA) level.

Plasma renin produces angiotensin II (Ang II) to constrict the arterioles and thereby ensure sufficient BP to deliver an appropriate rate of flow for cardiovascular homeostasis.

The low renin, sodium-volume dependent (V) form of essential hypertension occurs whenever body sodium content increases beyond the point where plasma renin–angiotensin vasoconstrictor activity is turned off. In contrast, medium to high renin (R) hypertension occurs when too much renin is secreted relative to the body sodium content.

Thus, BP = V × R.

This volume-vasoconstriction dual support of long-term hypertension is validated by the fact that all effective long-term antihypertensive drug types are either (i) natriuretic to reduce body salt and volume content (anti-V), or (ii) antirenin to reduce or block the activity of the circulating renin–angiotensin system (anti-R). The PRA test defines the relative participation of the concurrent volume and vasoconstrictor factors. In the hypertensive patient PRA testing can guide initiation, addition or subtraction of anti-V or anti-R antihypertensive drug types to thereby improve BP control and prognosis while reducing drug type usage and cost.

American Journal of Hypertension, advance online publication 22 September 2011; doi:10.1038/ajh.2011.171

angiotensin, blood pressure, hypertension, plasma renin activity, plasma renin test, PRA, renin, salt, sodium, vasoconstriction, volume

Dietary salt is often portrayed as a killer that causes high blood pressure (BP). At the same time renin is often portrayed as a villain that causes heart attacks, heart failure, renal failure, and strokes. To combat these problems salt is removed from diets, and diuretics and renin–angiotensin system blocking drugs are given.

But these approaches ignore the fact that the body salt and the circulating renin–angiotensin system play pivotal roles in determining the level of BP, to sustain an appropriate flow of blood to the tissues and thereby ensure the delivery of nutrients and the removal of metabolic products (Figure 1).

In this review, we describe how the plasma renin activity (PRA) test can be used to define the relative involvement of sodium-volume (V) and renin–angiotensin-vasoconstrictor (R) factors in determining BP, making it possible to identify whether a natriuretic anti-V or an antirenin–angiotensin anti-R drug is the correct drug type to effectively and efficiently treat the hypertension of the individual patient.

The interacting relationship between body sodium and the circulating renin–angiotensin system to maintain blood pressure, tissue blood flow, and tissue health. ACEI, angiotensin-converting enzyme inhibitor; Ang I, angiotensin I; ARB, angiotensin receptor blocker; BP, blood pressure; DRI, direct renin inhibitor; R, vasoconstrictor activity of the circulating renin–angiotensin system; V, body sodium-volume content

Open in new tabDownload slide

Physiology and Pathophysiology of the Renin–Angiotensin System

The physiological basis for the dual volume-vasoconstriction conception of BP control emerged from many years of clinical research.

1–4 It postulates that long-term BP–as opposed to minute to minute changes in BP–is sustained by two interacting forces: (i) the body sodium-volume content (V) and (ii) the plasma renin–angiotensin (R) vasoconstrictor activity.

This V and R interacting control system sustains all normotension, as well as all forms of hypertension–regardless of initiating cause.

This twin control of BP is in keeping with the long held view that arterial BP is sensitive to changes in body salt. It also recognizes that body salt does not affect BP directly but does so only by increasing or decreasing the extracellular fluid volume (ECF) and thus (assuming normal cardiac function) the volume of fluid delivered to the arterial tree.

This, per se affects arterial BP via an hydraulic effect. In addition, compensatory adjustments in arteriolar caliber are mediated by companion changes in circulating angiotensin II (Ang II).

This adjustment occurs whenever the cells of the renal juxtaglomerular apparatus of each nephron detect increases or decreases in body sodium-volume content and then alter their secretion of renin–downward or upward.

The vasoconstrictor effects of the induced changes in plasma Ang II, generated by PRA, alter the caliber of the arterioles thereby ensuring that BP is not significantly affected by changes in arterial sodium-volume. Thus, changes in body salt content are buffered by reciprocal changes in PRA to maintain BP homeostasis.

In the simplest of terms, arterial BP control can be viewed from the perspective of the 1828 Poiseuille equation: BP = cardiac output × peripheral resistance. In this equation the body sodium-volume content and PRA become functional surrogates for cardiac output and arteriolar resistance respectively: Thus, BP = (sodium-volume) × (PRA), or BP = V × R.

In this model, irrespective of the particular BP level, the degree of vasoconstriction caused by the circulating renin–angiotensin system is always proportional to the concurrent PRA level.

Thus, a normal BP level can be associated with low, medium or high PRA levels when it is concurrently associated with reciprocally high, medium or low levels of body sodium volume content respectively. From another perspective, the PRA level can be viewed as an index of whether the subject is salt depleted and hypovolemic, or instead is hypervolemic from a salt excess.

A high PRA level in a normotensive individual indicates some degree of body sodium-volume depletion, whereas a low PRA level indicates that body sodium-volume status is on the high side.

Long-term hypertension (as opposed to acute fluctuations in BP) occurs whenever the kidneys fail to induce a sufficient fall in PRA in response to an increase in body salt.

Hypertension may occur because renin secretion is already maximally suppressed, or because there is a defect in juxtaglomerular apparatus sensing mechanisms of individual nephrons that allows too much renin to be secreted for the level of body salt, or because there is overactivity of the sympathetic drive to renin release.

Whatever the reason, for hypertension to develop, PRA levels need not be higher than normal–just too high for the concurrent body sodium-volume content. This is why many hypertensive patients with renin-dependent hypertension exhibit PRA levels within the normal range.

Moreover, the reciprocals are also true. Whenever BP is successfully controlled, angiotensin-mediated vasoconstriction returns toward the medium range, indicating the return to an appropriate relationship to the body sodium-volume content to achieve optimal tissue flow.

The Anti-V and Anti-R Antihypertensive Drug Types

A fundamental verifying corollary of this volume-vasoconstriction dual servo-control system for long-term BP regulation is the fact that all effective antihypertensive drugs lower BP by either (i) reducing the body sodium-volume content or (ii) by reducing or blocking the vasoconstrictor activity of the circulating renin–angiotensin system.

5 This fits the underlying pathophysiology because all effective long-term antihypertensive drugs also fall into one of two categories: they are either (i) natriuretic agents that reduce body sodium-volume content–the anti-V drug types (i.e.

, sulfonamide diuretics, aldosterone receptor blockers, α-adrenergic blockers,6 calcium channel blockers7–9) or (ii) instead they reduce or block the vasoconstrictor activity of the circulating renin–angiotensin system–these are the antirenin system anti-R drugs (i.e., β-blockers, centrally acting agents (e.g.

, clonidine, guanfacine, reserpine), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), direct renin inhibitors (e.g., aliskiren)).

The classification of all available antihypertensive drugs into only two functional categories greatly simplifies drug treatment selection strategies because an enormous array of commercially available pharmaceutical agents (Table 1) and combinations thereof can be reduced to only two broad categories, either the natriuretic anti-V or the anti-R drugs (Table 2). This has enabled the development of relatively simple plasma renin-guided algorithms for the treatment of hypertension (discussed below).

How does the health care professional choose among the ten classes and 66 or more individual antihypertensive drugs?

The anti-V and anti-R categories of antihypertensive drugs

Studies That Led To the Volume-Vasoconstriction Analytical Model For Long-Term BP Control

These studies were grounded in Poisseuille's formula: (BP = cardiac output × peripheral resistance), in Tigerstedt's discovery of renin,10 in Goldblatt's renovascular model of hypertension,11 and in Conn's discovery of primary aldosteronism.

12 They matured as the biochemical components of the renin–angiotensin system were discovered,13 the sensing mechanisms of the renal juxtaglomerular apparatus were identified,14,15 and at a time when Guyton was identifying the over-riding dominance of the kidneys for sustaining hypertension.16

Body sodium content, PRA, and their interactive relationship to BP

The existence of two pathophysiological types of long-term hypertension became apparent during studies of malignant hypertension and of primary aldosteronism that led to our discovery of the link between the circulating renin–angiotensin system and adrenal cortical aldosterone secretion.

17–19 It became clear that these two clinical forms of hypertension were quite different; malignant hypertensive patients were very sick and died within a year whereas those with primary aldosteronism remained relatively healthy.

Thus, malignant hypertensive patients had very high levels of both plasma renin and the sodium-retaining hormone, aldosterone, whereas those with primary aldosteronism had very high aldosterone levels but very low plasma renin levels.

1,2 Thus, in more modern terms,5,20 malignant hypertension had both R and V hypertension, while primary aldosteronism had pure V hypertension with suppressed PRA.

The inter-relationships between body sodium content and PRA were examined in 1970 when Bull et al.

21 separately manipulated body sodium content as well as plasma and red blood cell volumes in six normal volunteers, who first underwent dietary and diuretic induced sodium-volume depletion during which PRA and aldosterone levels rose in parallel.

Then during dietary sodium repletion, PRA and aldosterone levels fell in parallel as urinary sodium excretion increased even though blood volume was held at low levels by daily plasmapheresis.

These findings indicate that expansion or contraction of the extracellular space is a more important determinant of sodium conservation or natriuresis than is the plasma or blood volume. In this model, body sodium-volume content exists in the extracellular fluids and is created by retained sodium chloride ions which hold enough water in the body to ensure that the ECF is isotonic.

The links between body sodium content and PRA were again revealed when urinary aldosterone excretion and PRA levels were measured in normal subjects (Figure 2) and in hypertensive patients during wide ranges of sodium intake and related to the 24-h urinary sodium excretion.22,23

Relationship of the 24-h urine sodium excretion (a reflection of the daily sodium intake) to the ambulatory plasma renin activity (PRA) level and to the 24-h urinary aldosterone excretion values in normal subjects (from Laragh et al.99). Because there were only three ambulatory PRA levels

Source: https://academic.oup.com/ajh/article/24/11/1164/2281914

Renin

What Is Renin? Blood Test & Low Renin Causes

Renin

What Is Renin? Blood Test & Low Renin Causes

Renin is a protein (enzyme) released by special kidney cells when you have decreased salt (sodium levels) or low blood volume.

Renin increases the amount of angiotensinogen in the blood, which eventually increases blood pressure. It increases the release of aldosterone, a hormone that helps control the body's salt and water balance.

This article discusses the test to measure the activity of renin in your blood.

Alternative Names

Alternative Names

Plasma renin activity; Random plasma renin; PRA

How the test is performed

How the test is performed

A blood sample is needed. For information on how this is done, see: Venipuncture

How to prepare for the test

How to prepare for the test

Your health care provider may tell you to temporarily stop taking certain drugs that can affect test results.

Drugs that can affect renin measurements include:

  • Birth control pills
  • Blood pressure medications
  • Diuretics
  • Vasodilators (drugs that enlarge blood vessels; they are usually used to treat high blood pressure or congestive heart failure)

You should eat a normal, balanced diet with moderate sodium content (about 3 gm/day) for 3 days before the test.

How the test will feel

How the test will feel

When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing.

Why the test is performed

Why the test is performed

This test is done as part of the diagnosis and treatment of high blood pressure.

If you have essential hypertension, your doctor may order a renin and aldosterone test to see if you are sensitive to salt (which causes low renin with normal aldosterone levels).

The test results may help to guide your doctor in choosing the correct medication. Salt-sensitive patients with high blood pressure associated with low renin levels respond well to diuretic medications.

Normal Values

Normal Values

Normal values range from 0.2 to 3.3 ng/mL/hour.

The examples above are common measurements for results of these tests. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your doctor about the meaning of your specific test results.

What abnormal results mean

What abnormal results mean

High levels of renin may be due to:

  • Addison's disease
  • Cirrhosis
  • Congestive heart failure
  • Dehydration
  • Hemorrhage (bleeding)
  • High blood pressure
  • Hypokalemia
  • Malignant hypertension
  • Nephrotic syndrome
  • Renin-producing renal tumors
  • Renovascular hypertension

Low renin levels may be due to:

  • ADH therapy
  • Hyperaldosteronism
  • Sodium-retaining steroid therapy
  • High blood pressure that is sodium-sensitive

What the risks are

What the risks are

Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others.

Other risks associated with having blood drawn are slight but may include:

  • Excessive bleeding
  • Fainting or feeling lightheaded
  • Hematoma (blood accumulating under the skin)
  • Infection (a slight risk any time the skin is broken)

Special considerations

Special considerations

Renin measurements are affected by salt intake, pregnancy, time of day, and body position.

References

Plasma Renin Test Reveals the Contribution of Body Sodium-Volume Content (V) and Renin–Angiotensin (R) Vasoconstriction to Long-Term Blood Pressure

What Is Renin? Blood Test & Low Renin Causes
What Is Renin? Blood Test & Low Renin Causes

Body sodium works together with the plasma renin–angiotensin system to ensure adequate blood flow to the tissues. Body sodium content determines the extracellular fluid (ECF) volume ensuring that, with each heart beat, a sufficient volume of fluid is delivered into the arterial space.

At the same time the kidneys monitor ECF volume and blood pressure (BP), so that the juxtaglomerular cells can adjust their net secretion rate of renin to maintain an appropriate plasma renin activity (PRA) level.

Plasma renin produces angiotensin II (Ang II) to constrict the arterioles and thereby ensure sufficient BP to deliver an appropriate rate of flow for cardiovascular homeostasis.

The low renin, sodium-volume dependent (V) form of essential hypertension occurs whenever body sodium content increases beyond the point where plasma renin–angiotensin vasoconstrictor activity is turned off. In contrast, medium to high renin (R) hypertension occurs when too much renin is secreted relative to the body sodium content.

Thus, BP = V × R.

This volume-vasoconstriction dual support of long-term hypertension is validated by the fact that all effective long-term antihypertensive drug types are either (i) natriuretic to reduce body salt and volume content (anti-V), or (ii) antirenin to reduce or block the activity of the circulating renin–angiotensin system (anti-R). The PRA test defines the relative participation of the concurrent volume and vasoconstrictor factors. In the hypertensive patient PRA testing can guide initiation, addition or subtraction of anti-V or anti-R antihypertensive drug types to thereby improve BP control and prognosis while reducing drug type usage and cost.

American Journal of Hypertension, advance online publication 22 September 2011; doi:10.1038/ajh.2011.171

angiotensin, blood pressure, hypertension, plasma renin activity, plasma renin test, PRA, renin, salt, sodium, vasoconstriction, volume

Dietary salt is often portrayed as a killer that causes high blood pressure (BP). At the same time renin is often portrayed as a villain that causes heart attacks, heart failure, renal failure, and strokes. To combat these problems salt is removed from diets, and diuretics and renin–angiotensin system blocking drugs are given.

But these approaches ignore the fact that the body salt and the circulating renin–angiotensin system play pivotal roles in determining the level of BP, to sustain an appropriate flow of blood to the tissues and thereby ensure the delivery of nutrients and the removal of metabolic products (Figure 1).

In this review, we describe how the plasma renin activity (PRA) test can be used to define the relative involvement of sodium-volume (V) and renin–angiotensin-vasoconstrictor (R) factors in determining BP, making it possible to identify whether a natriuretic anti-V or an antirenin–angiotensin anti-R drug is the correct drug type to effectively and efficiently treat the hypertension of the individual patient.

The interacting relationship between body sodium and the circulating renin–angiotensin system to maintain blood pressure, tissue blood flow, and tissue health. ACEI, angiotensin-converting enzyme inhibitor; Ang I, angiotensin I; ARB, angiotensin receptor blocker; BP, blood pressure; DRI, direct renin inhibitor; R, vasoconstrictor activity of the circulating renin–angiotensin system; V, body sodium-volume content

Open in new tabDownload slide

Physiology and Pathophysiology of the Renin–Angiotensin System

The physiological basis for the dual volume-vasoconstriction conception of BP control emerged from many years of clinical research.

1–4 It postulates that long-term BP–as opposed to minute to minute changes in BP–is sustained by two interacting forces: (i) the body sodium-volume content (V) and (ii) the plasma renin–angiotensin (R) vasoconstrictor activity.

This V and R interacting control system sustains all normotension, as well as all forms of hypertension–regardless of initiating cause.

This twin control of BP is in keeping with the long held view that arterial BP is sensitive to changes in body salt. It also recognizes that body salt does not affect BP directly but does so only by increasing or decreasing the extracellular fluid volume (ECF) and thus (assuming normal cardiac function) the volume of fluid delivered to the arterial tree.

This, per se affects arterial BP via an hydraulic effect. In addition, compensatory adjustments in arteriolar caliber are mediated by companion changes in circulating angiotensin II (Ang II).

This adjustment occurs whenever the cells of the renal juxtaglomerular apparatus of each nephron detect increases or decreases in body sodium-volume content and then alter their secretion of renin–downward or upward.

The vasoconstrictor effects of the induced changes in plasma Ang II, generated by PRA, alter the caliber of the arterioles thereby ensuring that BP is not significantly affected by changes in arterial sodium-volume. Thus, changes in body salt content are buffered by reciprocal changes in PRA to maintain BP homeostasis.

In the simplest of terms, arterial BP control can be viewed from the perspective of the 1828 Poiseuille equation: BP = cardiac output × peripheral resistance. In this equation the body sodium-volume content and PRA become functional surrogates for cardiac output and arteriolar resistance respectively: Thus, BP = (sodium-volume) × (PRA), or BP = V × R.

In this model, irrespective of the particular BP level, the degree of vasoconstriction caused by the circulating renin–angiotensin system is always proportional to the concurrent PRA level.

Thus, a normal BP level can be associated with low, medium or high PRA levels when it is concurrently associated with reciprocally high, medium or low levels of body sodium volume content respectively. From another perspective, the PRA level can be viewed as an index of whether the subject is salt depleted and hypovolemic, or instead is hypervolemic from a salt excess.

A high PRA level in a normotensive individual indicates some degree of body sodium-volume depletion, whereas a low PRA level indicates that body sodium-volume status is on the high side.

Long-term hypertension (as opposed to acute fluctuations in BP) occurs whenever the kidneys fail to induce a sufficient fall in PRA in response to an increase in body salt.

Hypertension may occur because renin secretion is already maximally suppressed, or because there is a defect in juxtaglomerular apparatus sensing mechanisms of individual nephrons that allows too much renin to be secreted for the level of body salt, or because there is overactivity of the sympathetic drive to renin release.

Whatever the reason, for hypertension to develop, PRA levels need not be higher than normal–just too high for the concurrent body sodium-volume content. This is why many hypertensive patients with renin-dependent hypertension exhibit PRA levels within the normal range.

Moreover, the reciprocals are also true. Whenever BP is successfully controlled, angiotensin-mediated vasoconstriction returns toward the medium range, indicating the return to an appropriate relationship to the body sodium-volume content to achieve optimal tissue flow.

The Anti-V and Anti-R Antihypertensive Drug Types

A fundamental verifying corollary of this volume-vasoconstriction dual servo-control system for long-term BP regulation is the fact that all effective antihypertensive drugs lower BP by either (i) reducing the body sodium-volume content or (ii) by reducing or blocking the vasoconstrictor activity of the circulating renin–angiotensin system.

5 This fits the underlying pathophysiology because all effective long-term antihypertensive drugs also fall into one of two categories: they are either (i) natriuretic agents that reduce body sodium-volume content–the anti-V drug types (i.e.

, sulfonamide diuretics, aldosterone receptor blockers, α-adrenergic blockers,6 calcium channel blockers7–9) or (ii) instead they reduce or block the vasoconstrictor activity of the circulating renin–angiotensin system–these are the antirenin system anti-R drugs (i.e., β-blockers, centrally acting agents (e.g.

, clonidine, guanfacine, reserpine), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), direct renin inhibitors (e.g., aliskiren)).

The classification of all available antihypertensive drugs into only two functional categories greatly simplifies drug treatment selection strategies because an enormous array of commercially available pharmaceutical agents (Table 1) and combinations thereof can be reduced to only two broad categories, either the natriuretic anti-V or the anti-R drugs (Table 2). This has enabled the development of relatively simple plasma renin-guided algorithms for the treatment of hypertension (discussed below).

How does the health care professional choose among the ten classes and 66 or more individual antihypertensive drugs?

The anti-V and anti-R categories of antihypertensive drugs

Studies That Led To the Volume-Vasoconstriction Analytical Model For Long-Term BP Control

These studies were grounded in Poisseuille's formula: (BP = cardiac output × peripheral resistance), in Tigerstedt's discovery of renin,10 in Goldblatt's renovascular model of hypertension,11 and in Conn's discovery of primary aldosteronism.

12 They matured as the biochemical components of the renin–angiotensin system were discovered,13 the sensing mechanisms of the renal juxtaglomerular apparatus were identified,14,15 and at a time when Guyton was identifying the over-riding dominance of the kidneys for sustaining hypertension.16

Body sodium content, PRA, and their interactive relationship to BP

The existence of two pathophysiological types of long-term hypertension became apparent during studies of malignant hypertension and of primary aldosteronism that led to our discovery of the link between the circulating renin–angiotensin system and adrenal cortical aldosterone secretion.

17–19 It became clear that these two clinical forms of hypertension were quite different; malignant hypertensive patients were very sick and died within a year whereas those with primary aldosteronism remained relatively healthy.

Thus, malignant hypertensive patients had very high levels of both plasma renin and the sodium-retaining hormone, aldosterone, whereas those with primary aldosteronism had very high aldosterone levels but very low plasma renin levels.

1,2 Thus, in more modern terms,5,20 malignant hypertension had both R and V hypertension, while primary aldosteronism had pure V hypertension with suppressed PRA.

The inter-relationships between body sodium content and PRA were examined in 1970 when Bull et al.

21 separately manipulated body sodium content as well as plasma and red blood cell volumes in six normal volunteers, who first underwent dietary and diuretic induced sodium-volume depletion during which PRA and aldosterone levels rose in parallel.

Then during dietary sodium repletion, PRA and aldosterone levels fell in parallel as urinary sodium excretion increased even though blood volume was held at low levels by daily plasmapheresis.

These findings indicate that expansion or contraction of the extracellular space is a more important determinant of sodium conservation or natriuresis than is the plasma or blood volume. In this model, body sodium-volume content exists in the extracellular fluids and is created by retained sodium chloride ions which hold enough water in the body to ensure that the ECF is isotonic.

The links between body sodium content and PRA were again revealed when urinary aldosterone excretion and PRA levels were measured in normal subjects (Figure 2) and in hypertensive patients during wide ranges of sodium intake and related to the 24-h urinary sodium excretion.22,23

Relationship of the 24-h urine sodium excretion (a reflection of the daily sodium intake) to the ambulatory plasma renin activity (PRA) level and to the 24-h urinary aldosterone excretion values in normal subjects (from Laragh et al.99). Because there were only three ambulatory PRA levels

Source: https://academic.oup.com/ajh/article/24/11/1164/2281914

Renin

What Is Renin? Blood Test & Low Renin Causes

Renin is a protein (enzyme) released by special kidney cells when you have decreased salt (sodium levels) or low blood volume.

Renin increases the amount of angiotensinogen in the blood, which eventually increases blood pressure. It increases the release of aldosterone, a hormone that helps control the body's salt and water balance.

This article discusses the test to measure the activity of renin in your blood.

Alternative Names

Plasma renin activity; Random plasma renin; PRA

How the test is performed

A blood sample is needed. For information on how this is done, see: Venipuncture

How to prepare for the test

Your health care provider may tell you to temporarily stop taking certain drugs that can affect test results.

Drugs that can affect renin measurements include:

  • Birth control pills
  • Blood pressure medications
  • Diuretics
  • Vasodilators (drugs that enlarge blood vessels; they are usually used to treat high blood pressure or congestive heart failure)

You should eat a normal, balanced diet with moderate sodium content (about 3 gm/day) for 3 days before the test.

How the test will feel

When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing.

Why the test is performed

This test is done as part of the diagnosis and treatment of high blood pressure.

If you have essential hypertension, your doctor may order a renin and aldosterone test to see if you are sensitive to salt (which causes low renin with normal aldosterone levels).

The test results may help to guide your doctor in choosing the correct medication. Salt-sensitive patients with high blood pressure associated with low renin levels respond well to diuretic medications.

Normal Values

Normal values range from 0.2 to 3.3 ng/mL/hour.

The examples above are common measurements for results of these tests. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your doctor about the meaning of your specific test results.

What abnormal results mean

High levels of renin may be due to:

  • Addison's disease
  • Cirrhosis
  • Congestive heart failure
  • Dehydration
  • Hemorrhage (bleeding)
  • High blood pressure
  • Hypokalemia
  • Malignant hypertension
  • Nephrotic syndrome
  • Renin-producing renal tumors
  • Renovascular hypertension

Low renin levels may be due to:

  • ADH therapy
  • Hyperaldosteronism
  • Sodium-retaining steroid therapy
  • High blood pressure that is sodium-sensitive

What the risks are

Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others.

Other risks associated with having blood drawn are slight but may include:

  • Excessive bleeding
  • Fainting or feeling lightheaded
  • Hematoma (blood accumulating under the skin)
  • Infection (a slight risk any time the skin is broken)

Special considerations

Renin measurements are affected by salt intake, pregnancy, time of day, and body position.

Plasma Renin Test Reveals the Contribution of Body Sodium-Volume Content (V) and Renin–Angiotensin (R) Vasoconstriction to Long-Term Blood Pressure

What Is Renin? Blood Test & Low Renin Causes
What Is Renin? Blood Test & Low Renin Causes

Body sodium works together with the plasma renin–angiotensin system to ensure adequate blood flow to the tissues. Body sodium content determines the extracellular fluid (ECF) volume ensuring that, with each heart beat, a sufficient volume of fluid is delivered into the arterial space.

At the same time the kidneys monitor ECF volume and blood pressure (BP), so that the juxtaglomerular cells can adjust their net secretion rate of renin to maintain an appropriate plasma renin activity (PRA) level.

Plasma renin produces angiotensin II (Ang II) to constrict the arterioles and thereby ensure sufficient BP to deliver an appropriate rate of flow for cardiovascular homeostasis.

The low renin, sodium-volume dependent (V) form of essential hypertension occurs whenever body sodium content increases beyond the point where plasma renin–angiotensin vasoconstrictor activity is turned off. In contrast, medium to high renin (R) hypertension occurs when too much renin is secreted relative to the body sodium content.

Thus, BP = V × R.

This volume-vasoconstriction dual support of long-term hypertension is validated by the fact that all effective long-term antihypertensive drug types are either (i) natriuretic to reduce body salt and volume content (anti-V), or (ii) antirenin to reduce or block the activity of the circulating renin–angiotensin system (anti-R). The PRA test defines the relative participation of the concurrent volume and vasoconstrictor factors. In the hypertensive patient PRA testing can guide initiation, addition or subtraction of anti-V or anti-R antihypertensive drug types to thereby improve BP control and prognosis while reducing drug type usage and cost.

American Journal of Hypertension, advance online publication 22 September 2011; doi:10.1038/ajh.2011.171

angiotensin, blood pressure, hypertension, plasma renin activity, plasma renin test, PRA, renin, salt, sodium, vasoconstriction, volume

Dietary salt is often portrayed as a killer that causes high blood pressure (BP). At the same time renin is often portrayed as a villain that causes heart attacks, heart failure, renal failure, and strokes. To combat these problems salt is removed from diets, and diuretics and renin–angiotensin system blocking drugs are given.

But these approaches ignore the fact that the body salt and the circulating renin–angiotensin system play pivotal roles in determining the level of BP, to sustain an appropriate flow of blood to the tissues and thereby ensure the delivery of nutrients and the removal of metabolic products (Figure 1).

In this review, we describe how the plasma renin activity (PRA) test can be used to define the relative involvement of sodium-volume (V) and renin–angiotensin-vasoconstrictor (R) factors in determining BP, making it possible to identify whether a natriuretic anti-V or an antirenin–angiotensin anti-R drug is the correct drug type to effectively and efficiently treat the hypertension of the individual patient.

The interacting relationship between body sodium and the circulating renin–angiotensin system to maintain blood pressure, tissue blood flow, and tissue health. ACEI, angiotensin-converting enzyme inhibitor; Ang I, angiotensin I; ARB, angiotensin receptor blocker; BP, blood pressure; DRI, direct renin inhibitor; R, vasoconstrictor activity of the circulating renin–angiotensin system; V, body sodium-volume content

Open in new tabDownload slide

Physiology and Pathophysiology of the Renin–Angiotensin System

The physiological basis for the dual volume-vasoconstriction conception of BP control emerged from many years of clinical research.

1–4 It postulates that long-term BP–as opposed to minute to minute changes in BP–is sustained by two interacting forces: (i) the body sodium-volume content (V) and (ii) the plasma renin–angiotensin (R) vasoconstrictor activity.

This V and R interacting control system sustains all normotension, as well as all forms of hypertension–regardless of initiating cause.

This twin control of BP is in keeping with the long held view that arterial BP is sensitive to changes in body salt. It also recognizes that body salt does not affect BP directly but does so only by increasing or decreasing the extracellular fluid volume (ECF) and thus (assuming normal cardiac function) the volume of fluid delivered to the arterial tree.

This, per se affects arterial BP via an hydraulic effect. In addition, compensatory adjustments in arteriolar caliber are mediated by companion changes in circulating angiotensin II (Ang II).

This adjustment occurs whenever the cells of the renal juxtaglomerular apparatus of each nephron detect increases or decreases in body sodium-volume content and then alter their secretion of renin–downward or upward.

The vasoconstrictor effects of the induced changes in plasma Ang II, generated by PRA, alter the caliber of the arterioles thereby ensuring that BP is not significantly affected by changes in arterial sodium-volume. Thus, changes in body salt content are buffered by reciprocal changes in PRA to maintain BP homeostasis.

In the simplest of terms, arterial BP control can be viewed from the perspective of the 1828 Poiseuille equation: BP = cardiac output × peripheral resistance. In this equation the body sodium-volume content and PRA become functional surrogates for cardiac output and arteriolar resistance respectively: Thus, BP = (sodium-volume) × (PRA), or BP = V × R.

In this model, irrespective of the particular BP level, the degree of vasoconstriction caused by the circulating renin–angiotensin system is always proportional to the concurrent PRA level.

Thus, a normal BP level can be associated with low, medium or high PRA levels when it is concurrently associated with reciprocally high, medium or low levels of body sodium volume content respectively. From another perspective, the PRA level can be viewed as an index of whether the subject is salt depleted and hypovolemic, or instead is hypervolemic from a salt excess.

A high PRA level in a normotensive individual indicates some degree of body sodium-volume depletion, whereas a low PRA level indicates that body sodium-volume status is on the high side.

Long-term hypertension (as opposed to acute fluctuations in BP) occurs whenever the kidneys fail to induce a sufficient fall in PRA in response to an increase in body salt.

Hypertension may occur because renin secretion is already maximally suppressed, or because there is a defect in juxtaglomerular apparatus sensing mechanisms of individual nephrons that allows too much renin to be secreted for the level of body salt, or because there is overactivity of the sympathetic drive to renin release.

Whatever the reason, for hypertension to develop, PRA levels need not be higher than normal–just too high for the concurrent body sodium-volume content. This is why many hypertensive patients with renin-dependent hypertension exhibit PRA levels within the normal range.

Moreover, the reciprocals are also true. Whenever BP is successfully controlled, angiotensin-mediated vasoconstriction returns toward the medium range, indicating the return to an appropriate relationship to the body sodium-volume content to achieve optimal tissue flow.

The Anti-V and Anti-R Antihypertensive Drug Types

A fundamental verifying corollary of this volume-vasoconstriction dual servo-control system for long-term BP regulation is the fact that all effective antihypertensive drugs lower BP by either (i) reducing the body sodium-volume content or (ii) by reducing or blocking the vasoconstrictor activity of the circulating renin–angiotensin system.

5 This fits the underlying pathophysiology because all effective long-term antihypertensive drugs also fall into one of two categories: they are either (i) natriuretic agents that reduce body sodium-volume content–the anti-V drug types (i.e.

, sulfonamide diuretics, aldosterone receptor blockers, α-adrenergic blockers,6 calcium channel blockers7–9) or (ii) instead they reduce or block the vasoconstrictor activity of the circulating renin–angiotensin system–these are the antirenin system anti-R drugs (i.e., β-blockers, centrally acting agents (e.g.

, clonidine, guanfacine, reserpine), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), direct renin inhibitors (e.g., aliskiren)).

The classification of all available antihypertensive drugs into only two functional categories greatly simplifies drug treatment selection strategies because an enormous array of commercially available pharmaceutical agents (Table 1) and combinations thereof can be reduced to only two broad categories, either the natriuretic anti-V or the anti-R drugs (Table 2). This has enabled the development of relatively simple plasma renin-guided algorithms for the treatment of hypertension (discussed below).

How does the health care professional choose among the ten classes and 66 or more individual antihypertensive drugs?

The anti-V and anti-R categories of antihypertensive drugs

Studies That Led To the Volume-Vasoconstriction Analytical Model For Long-Term BP Control

These studies were grounded in Poisseuille's formula: (BP = cardiac output × peripheral resistance), in Tigerstedt's discovery of renin,10 in Goldblatt's renovascular model of hypertension,11 and in Conn's discovery of primary aldosteronism.

12 They matured as the biochemical components of the renin–angiotensin system were discovered,13 the sensing mechanisms of the renal juxtaglomerular apparatus were identified,14,15 and at a time when Guyton was identifying the over-riding dominance of the kidneys for sustaining hypertension.16

Body sodium content, PRA, and their interactive relationship to BP

The existence of two pathophysiological types of long-term hypertension became apparent during studies of malignant hypertension and of primary aldosteronism that led to our discovery of the link between the circulating renin–angiotensin system and adrenal cortical aldosterone secretion.

17–19 It became clear that these two clinical forms of hypertension were quite different; malignant hypertensive patients were very sick and died within a year whereas those with primary aldosteronism remained relatively healthy.

Thus, malignant hypertensive patients had very high levels of both plasma renin and the sodium-retaining hormone, aldosterone, whereas those with primary aldosteronism had very high aldosterone levels but very low plasma renin levels.

1,2 Thus, in more modern terms,5,20 malignant hypertension had both R and V hypertension, while primary aldosteronism had pure V hypertension with suppressed PRA.

The inter-relationships between body sodium content and PRA were examined in 1970 when Bull et al.

21 separately manipulated body sodium content as well as plasma and red blood cell volumes in six normal volunteers, who first underwent dietary and diuretic induced sodium-volume depletion during which PRA and aldosterone levels rose in parallel.

Then during dietary sodium repletion, PRA and aldosterone levels fell in parallel as urinary sodium excretion increased even though blood volume was held at low levels by daily plasmapheresis.

These findings indicate that expansion or contraction of the extracellular space is a more important determinant of sodium conservation or natriuresis than is the plasma or blood volume. In this model, body sodium-volume content exists in the extracellular fluids and is created by retained sodium chloride ions which hold enough water in the body to ensure that the ECF is isotonic.

The links between body sodium content and PRA were again revealed when urinary aldosterone excretion and PRA levels were measured in normal subjects (Figure 2) and in hypertensive patients during wide ranges of sodium intake and related to the 24-h urinary sodium excretion.22,23

Relationship of the 24-h urine sodium excretion (a reflection of the daily sodium intake) to the ambulatory plasma renin activity (PRA) level and to the 24-h urinary aldosterone excretion values in normal subjects (from Laragh et al.99). Because there were only three ambulatory PRA levels

Source: https://academic.oup.com/ajh/article/24/11/1164/2281914

Renin

What Is Renin? Blood Test & Low Renin Causes

Renin

What Is Renin? Blood Test & Low Renin Causes

Renin is a protein (enzyme) released by special kidney cells when you have decreased salt (sodium levels) or low blood volume.

Renin increases the amount of angiotensinogen in the blood, which eventually increases blood pressure. It increases the release of aldosterone, a hormone that helps control the body's salt and water balance.

This article discusses the test to measure the activity of renin in your blood.

Alternative Names

Alternative Names

Plasma renin activity; Random plasma renin; PRA

How the test is performed

How the test is performed

A blood sample is needed. For information on how this is done, see: Venipuncture

How to prepare for the test

How to prepare for the test

Your health care provider may tell you to temporarily stop taking certain drugs that can affect test results.

Drugs that can affect renin measurements include:

  • Birth control pills
  • Blood pressure medications
  • Diuretics
  • Vasodilators (drugs that enlarge blood vessels; they are usually used to treat high blood pressure or congestive heart failure)

You should eat a normal, balanced diet with moderate sodium content (about 3 gm/day) for 3 days before the test.

How the test will feel

How the test will feel

When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing.

Why the test is performed

Why the test is performed

This test is done as part of the diagnosis and treatment of high blood pressure.

If you have essential hypertension, your doctor may order a renin and aldosterone test to see if you are sensitive to salt (which causes low renin with normal aldosterone levels).

The test results may help to guide your doctor in choosing the correct medication. Salt-sensitive patients with high blood pressure associated with low renin levels respond well to diuretic medications.

Normal Values

Normal Values

Normal values range from 0.2 to 3.3 ng/mL/hour.

The examples above are common measurements for results of these tests. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your doctor about the meaning of your specific test results.

What abnormal results mean

What abnormal results mean

High levels of renin may be due to:

  • Addison's disease
  • Cirrhosis
  • Congestive heart failure
  • Dehydration
  • Hemorrhage (bleeding)
  • High blood pressure
  • Hypokalemia
  • Malignant hypertension
  • Nephrotic syndrome
  • Renin-producing renal tumors
  • Renovascular hypertension

Low renin levels may be due to:

  • ADH therapy
  • Hyperaldosteronism
  • Sodium-retaining steroid therapy
  • High blood pressure that is sodium-sensitive

What the risks are

What the risks are

Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others.

Other risks associated with having blood drawn are slight but may include:

  • Excessive bleeding
  • Fainting or feeling lightheaded
  • Hematoma (blood accumulating under the skin)
  • Infection (a slight risk any time the skin is broken)

Special considerations

Special considerations

Renin measurements are affected by salt intake, pregnancy, time of day, and body position.

References

Plasma Renin Test Reveals the Contribution of Body Sodium-Volume Content (V) and Renin–Angiotensin (R) Vasoconstriction to Long-Term Blood Pressure

What Is Renin? Blood Test & Low Renin Causes
What Is Renin? Blood Test & Low Renin Causes

Body sodium works together with the plasma renin–angiotensin system to ensure adequate blood flow to the tissues. Body sodium content determines the extracellular fluid (ECF) volume ensuring that, with each heart beat, a sufficient volume of fluid is delivered into the arterial space.

At the same time the kidneys monitor ECF volume and blood pressure (BP), so that the juxtaglomerular cells can adjust their net secretion rate of renin to maintain an appropriate plasma renin activity (PRA) level.

Plasma renin produces angiotensin II (Ang II) to constrict the arterioles and thereby ensure sufficient BP to deliver an appropriate rate of flow for cardiovascular homeostasis.

The low renin, sodium-volume dependent (V) form of essential hypertension occurs whenever body sodium content increases beyond the point where plasma renin–angiotensin vasoconstrictor activity is turned off. In contrast, medium to high renin (R) hypertension occurs when too much renin is secreted relative to the body sodium content.

Thus, BP = V × R.

This volume-vasoconstriction dual support of long-term hypertension is validated by the fact that all effective long-term antihypertensive drug types are either (i) natriuretic to reduce body salt and volume content (anti-V), or (ii) antirenin to reduce or block the activity of the circulating renin–angiotensin system (anti-R). The PRA test defines the relative participation of the concurrent volume and vasoconstrictor factors. In the hypertensive patient PRA testing can guide initiation, addition or subtraction of anti-V or anti-R antihypertensive drug types to thereby improve BP control and prognosis while reducing drug type usage and cost.

American Journal of Hypertension, advance online publication 22 September 2011; doi:10.1038/ajh.2011.171

angiotensin, blood pressure, hypertension, plasma renin activity, plasma renin test, PRA, renin, salt, sodium, vasoconstriction, volume

Dietary salt is often portrayed as a killer that causes high blood pressure (BP). At the same time renin is often portrayed as a villain that causes heart attacks, heart failure, renal failure, and strokes. To combat these problems salt is removed from diets, and diuretics and renin–angiotensin system blocking drugs are given.

But these approaches ignore the fact that the body salt and the circulating renin–angiotensin system play pivotal roles in determining the level of BP, to sustain an appropriate flow of blood to the tissues and thereby ensure the delivery of nutrients and the removal of metabolic products (Figure 1).

In this review, we describe how the plasma renin activity (PRA) test can be used to define the relative involvement of sodium-volume (V) and renin–angiotensin-vasoconstrictor (R) factors in determining BP, making it possible to identify whether a natriuretic anti-V or an antirenin–angiotensin anti-R drug is the correct drug type to effectively and efficiently treat the hypertension of the individual patient.

The interacting relationship between body sodium and the circulating renin–angiotensin system to maintain blood pressure, tissue blood flow, and tissue health. ACEI, angiotensin-converting enzyme inhibitor; Ang I, angiotensin I; ARB, angiotensin receptor blocker; BP, blood pressure; DRI, direct renin inhibitor; R, vasoconstrictor activity of the circulating renin–angiotensin system; V, body sodium-volume content

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Physiology and Pathophysiology of the Renin–Angiotensin System

The physiological basis for the dual volume-vasoconstriction conception of BP control emerged from many years of clinical research.

1–4 It postulates that long-term BP–as opposed to minute to minute changes in BP–is sustained by two interacting forces: (i) the body sodium-volume content (V) and (ii) the plasma renin–angiotensin (R) vasoconstrictor activity.

This V and R interacting control system sustains all normotension, as well as all forms of hypertension–regardless of initiating cause.

This twin control of BP is in keeping with the long held view that arterial BP is sensitive to changes in body salt. It also recognizes that body salt does not affect BP directly but does so only by increasing or decreasing the extracellular fluid volume (ECF) and thus (assuming normal cardiac function) the volume of fluid delivered to the arterial tree.

This, per se affects arterial BP via an hydraulic effect. In addition, compensatory adjustments in arteriolar caliber are mediated by companion changes in circulating angiotensin II (Ang II).

This adjustment occurs whenever the cells of the renal juxtaglomerular apparatus of each nephron detect increases or decreases in body sodium-volume content and then alter their secretion of renin–downward or upward.

The vasoconstrictor effects of the induced changes in plasma Ang II, generated by PRA, alter the caliber of the arterioles thereby ensuring that BP is not significantly affected by changes in arterial sodium-volume. Thus, changes in body salt content are buffered by reciprocal changes in PRA to maintain BP homeostasis.

In the simplest of terms, arterial BP control can be viewed from the perspective of the 1828 Poiseuille equation: BP = cardiac output × peripheral resistance. In this equation the body sodium-volume content and PRA become functional surrogates for cardiac output and arteriolar resistance respectively: Thus, BP = (sodium-volume) × (PRA), or BP = V × R.

In this model, irrespective of the particular BP level, the degree of vasoconstriction caused by the circulating renin–angiotensin system is always proportional to the concurrent PRA level.

Thus, a normal BP level can be associated with low, medium or high PRA levels when it is concurrently associated with reciprocally high, medium or low levels of body sodium volume content respectively. From another perspective, the PRA level can be viewed as an index of whether the subject is salt depleted and hypovolemic, or instead is hypervolemic from a salt excess.

A high PRA level in a normotensive individual indicates some degree of body sodium-volume depletion, whereas a low PRA level indicates that body sodium-volume status is on the high side.

Long-term hypertension (as opposed to acute fluctuations in BP) occurs whenever the kidneys fail to induce a sufficient fall in PRA in response to an increase in body salt.

Hypertension may occur because renin secretion is already maximally suppressed, or because there is a defect in juxtaglomerular apparatus sensing mechanisms of individual nephrons that allows too much renin to be secreted for the level of body salt, or because there is overactivity of the sympathetic drive to renin release.

Whatever the reason, for hypertension to develop, PRA levels need not be higher than normal–just too high for the concurrent body sodium-volume content. This is why many hypertensive patients with renin-dependent hypertension exhibit PRA levels within the normal range.

Moreover, the reciprocals are also true. Whenever BP is successfully controlled, angiotensin-mediated vasoconstriction returns toward the medium range, indicating the return to an appropriate relationship to the body sodium-volume content to achieve optimal tissue flow.

The Anti-V and Anti-R Antihypertensive Drug Types

A fundamental verifying corollary of this volume-vasoconstriction dual servo-control system for long-term BP regulation is the fact that all effective antihypertensive drugs lower BP by either (i) reducing the body sodium-volume content or (ii) by reducing or blocking the vasoconstrictor activity of the circulating renin–angiotensin system.

5 This fits the underlying pathophysiology because all effective long-term antihypertensive drugs also fall into one of two categories: they are either (i) natriuretic agents that reduce body sodium-volume content–the anti-V drug types (i.e.

, sulfonamide diuretics, aldosterone receptor blockers, α-adrenergic blockers,6 calcium channel blockers7–9) or (ii) instead they reduce or block the vasoconstrictor activity of the circulating renin–angiotensin system–these are the antirenin system anti-R drugs (i.e., β-blockers, centrally acting agents (e.g.

, clonidine, guanfacine, reserpine), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), direct renin inhibitors (e.g., aliskiren)).

The classification of all available antihypertensive drugs into only two functional categories greatly simplifies drug treatment selection strategies because an enormous array of commercially available pharmaceutical agents (Table 1) and combinations thereof can be reduced to only two broad categories, either the natriuretic anti-V or the anti-R drugs (Table 2). This has enabled the development of relatively simple plasma renin-guided algorithms for the treatment of hypertension (discussed below).

How does the health care professional choose among the ten classes and 66 or more individual antihypertensive drugs?

The anti-V and anti-R categories of antihypertensive drugs

Studies That Led To the Volume-Vasoconstriction Analytical Model For Long-Term BP Control

These studies were grounded in Poisseuille's formula: (BP = cardiac output × peripheral resistance), in Tigerstedt's discovery of renin,10 in Goldblatt's renovascular model of hypertension,11 and in Conn's discovery of primary aldosteronism.

12 They matured as the biochemical components of the renin–angiotensin system were discovered,13 the sensing mechanisms of the renal juxtaglomerular apparatus were identified,14,15 and at a time when Guyton was identifying the over-riding dominance of the kidneys for sustaining hypertension.16

Body sodium content, PRA, and their interactive relationship to BP

The existence of two pathophysiological types of long-term hypertension became apparent during studies of malignant hypertension and of primary aldosteronism that led to our discovery of the link between the circulating renin–angiotensin system and adrenal cortical aldosterone secretion.

17–19 It became clear that these two clinical forms of hypertension were quite different; malignant hypertensive patients were very sick and died within a year whereas those with primary aldosteronism remained relatively healthy.

Thus, malignant hypertensive patients had very high levels of both plasma renin and the sodium-retaining hormone, aldosterone, whereas those with primary aldosteronism had very high aldosterone levels but very low plasma renin levels.

1,2 Thus, in more modern terms,5,20 malignant hypertension had both R and V hypertension, while primary aldosteronism had pure V hypertension with suppressed PRA.

The inter-relationships between body sodium content and PRA were examined in 1970 when Bull et al.

21 separately manipulated body sodium content as well as plasma and red blood cell volumes in six normal volunteers, who first underwent dietary and diuretic induced sodium-volume depletion during which PRA and aldosterone levels rose in parallel.

Then during dietary sodium repletion, PRA and aldosterone levels fell in parallel as urinary sodium excretion increased even though blood volume was held at low levels by daily plasmapheresis.

These findings indicate that expansion or contraction of the extracellular space is a more important determinant of sodium conservation or natriuresis than is the plasma or blood volume. In this model, body sodium-volume content exists in the extracellular fluids and is created by retained sodium chloride ions which hold enough water in the body to ensure that the ECF is isotonic.

The links between body sodium content and PRA were again revealed when urinary aldosterone excretion and PRA levels were measured in normal subjects (Figure 2) and in hypertensive patients during wide ranges of sodium intake and related to the 24-h urinary sodium excretion.22,23

Relationship of the 24-h urine sodium excretion (a reflection of the daily sodium intake) to the ambulatory plasma renin activity (PRA) level and to the 24-h urinary aldosterone excretion values in normal subjects (from Laragh et al.99). Because there were only three ambulatory PRA levels

Source: https://academic.oup.com/ajh/article/24/11/1164/2281914

Renin

What Is Renin? Blood Test & Low Renin Causes

Renin is a protein (enzyme) released by special kidney cells when you have decreased salt (sodium levels) or low blood volume.

Renin increases the amount of angiotensinogen in the blood, which eventually increases blood pressure. It increases the release of aldosterone, a hormone that helps control the body's salt and water balance.

This article discusses the test to measure the activity of renin in your blood.

Alternative Names

Plasma renin activity; Random plasma renin; PRA

How the test is performed

A blood sample is needed. For information on how this is done, see: Venipuncture

How to prepare for the test

Your health care provider may tell you to temporarily stop taking certain drugs that can affect test results.

Drugs that can affect renin measurements include:

  • Birth control pills
  • Blood pressure medications
  • Diuretics
  • Vasodilators (drugs that enlarge blood vessels; they are usually used to treat high blood pressure or congestive heart failure)

You should eat a normal, balanced diet with moderate sodium content (about 3 gm/day) for 3 days before the test.

How the test will feel

When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing.

Why the test is performed

This test is done as part of the diagnosis and treatment of high blood pressure.

If you have essential hypertension, your doctor may order a renin and aldosterone test to see if you are sensitive to salt (which causes low renin with normal aldosterone levels).

The test results may help to guide your doctor in choosing the correct medication. Salt-sensitive patients with high blood pressure associated with low renin levels respond well to diuretic medications.

Normal Values

Normal values range from 0.2 to 3.3 ng/mL/hour.

The examples above are common measurements for results of these tests. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your doctor about the meaning of your specific test results.

What abnormal results mean

High levels of renin may be due to:

  • Addison's disease
  • Cirrhosis
  • Congestive heart failure
  • Dehydration
  • Hemorrhage (bleeding)
  • High blood pressure
  • Hypokalemia
  • Malignant hypertension
  • Nephrotic syndrome
  • Renin-producing renal tumors
  • Renovascular hypertension

Low renin levels may be due to:

  • ADH therapy
  • Hyperaldosteronism
  • Sodium-retaining steroid therapy
  • High blood pressure that is sodium-sensitive

What the risks are

Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others.

Other risks associated with having blood drawn are slight but may include:

  • Excessive bleeding
  • Fainting or feeling lightheaded
  • Hematoma (blood accumulating under the skin)
  • Infection (a slight risk any time the skin is broken)

Special considerations

Renin measurements are affected by salt intake, pregnancy, time of day, and body position.

References

Victor RG. Arterial hypertension. In: Goldman L, Schafer AI, eds. Cecil Medicine. 24th ed. Philadelphia, Pa: Saunders Elsevier; 2011:chap 67.

Blumenfeld JD, Liu F, Laragh JR. Primary and secondary hypertension. In: Taal MW, Chertow GM, Marsden PA, Skorecki K, Yu ASL, Brenner BM, eds. Brenner & Rector's The Kidney. 9th ed. Philadelphia, PA: Saunders Elsevier; 2011:chap 46.

Review Date: 9/3/2012

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