OPERATIVE AND NONOPERATIVE
HYPERTENSION
Recent Advances in Treatment RICHARD
H. BARD.
M.D.
From the Urology Service, Department of Surgery, Montefiore Hospital and Medical Center, and Albert Einstein College of Medicine, New York, New York
ABSTRACT -In the past five years there have been signijcant advances in the diagnosis and treatment of operative and nonoperative forms of hypertension. Several areas of specijic interest to urologists will be discussed.
Hypertension is probably the most common disease-producing entity in the United States, affecting an estimated 16 per cent of the adult population, Cardiovascular complications of elevated blood pressure include heart disease, cerebral hemorrhage/stroke, renal failure, and blindness. The Veterans Administration Cooperative Study has conclusively demonstrated that even moderate elevations in diastolic blood pressure are associated with significantly shortened life expectancy. A diastolic blood pressure of95 mm. Hg in males age thirty-five to forty-five increases the mortality two and one-half times, and a diastolic pressure of 100 mm. Hg increases the mortality rate five times.’ It is now agreed that a considerable number of hypertensive diseases can be treated surgically (Table I). A conservative estimate indicates that there are more than a million people with renovascular hypertension nationwide who might benefit from surgical intervention. In a recent highly selective series, renovascular hypertensives comprised 15 to 16 per cent,’ although the accepted figure for renovascular hypertensive individuals in the general hypertensive population is 4 per cent. This is of paramount importance to urologists, especially in large metropolitan areas where such cases tend to be clustered. An examPresented at the Seventy-Third Annual Meeting, Section of the American Urological Association, Bermuda, September 21-25, 1975.
UROLOGY
/ MARCH1976
/ VOLUMEVII,
New York Hamilton,
NUMBER3
ple of this is the estimated 74,000 to 102,000 potentially operable hypertensives within a thirty mile radius of New York City. The obvious problem is in clearly identifying this group. The approach to working up the hypertensive patient involves patience, persistence, and clinical intuition. Most hypertensive patients being evaluated by urologists are referred by their internists. However, it should be a routine practice to obtain each new patient’s blood pressure as a screening measure. Any patient having three consecutive blood pressure determinations of 140/90 mm. Hg or greater by the same observer on three separate occasions must be considered to be hypertensive. I. Surgically correctable hypertensive diseases *
TABLE
Disease Essential hypertension Renal parenchymal Renovascular Coarctation of aorta Primary aldosteronism Cushing’s syndrome Pheochromocytoma Other *Estimated hypertensive
Per Cent 89
Population .
.
5 1
840,& tdl,&O,OOO 210,000 to 300,000
0.5 0.2 0.2 0.1
105,000 to 150,ooo 42,000 to 60,000 42,000 to 60,000 . . .
4
that 10 to 15 per cent of U.S. (21 to 30 million individuals).
population
is
239
Hypertensive
Evaluation
The pertinent steps in the hypertensive evaluation are as follows: A. History and physical examination B. Laboratory and diagnostic studies Urinalysis, urine culture Complete blood count, serum electrolytes, creatinine clearance, fasting blood sugar, blood urea nitrogen, serum calcium, phosphorus, uric acid, creatinine, T4, serum cholesterol, and fasting triglycerides Electrocardiogram, chest roentgenogram Twenty-four-hour urine for 17-ketosteroids and 17-OH steroids Urinary catecholamine screening test Rapid sequence intravenous pyelogram Renal scan and/or radioactive renogram (optional in initial evaluation but suggested for complete work-up) C. Results of findings If intravenous pyelogram is abnormal or there is a history of recent onset or rapidly progressive elevations in blood pressure, proceed with: Peripheral blood plasma renin activity (regular diet, upright posture) If peripheral renin is elevated: Renal vein and aortic catheterization for plasma renin activity. Renal arteriogram may be performed at the same time D. If blood pressure elevations are mild, the patient elderly, or if medical status makes surgery dangerous, antihypertensive drugs should be given. If a significant lesion is present, surgery is indicated. If the initial screening studies are negative, it is safe to assume that the patient has only a slim possibility of secondary hypertension and should be treated medically. All other patients should be considered to have potentially curable surgical lesions and should have a renal scan and selective renal arteriogram with concomitant collection of renal vein renins. Of 78 patients thoroughly evaluated for hypertension at the Presbyterian Hospital in New York City from 1967 to 1969, a surprisingly high percentage were found to have surgically correctable conditions who presented with hypertension as their principal physical finding (Fig. 1). These included renal and adrenal tumors, renal artery aneurysm, renal artery stenosis, hydronephrosis, and coarctation of the aorta. In all, a total of 26 of the 78 hypertensive patients underwent some type of surgical procedure (33 per cent). This is not to infer that these statistics apply to the general population. However, one is impressed with
240
the variety of pathologic disorders that present themselves in the disguise of elevated blood pressure. There is little doubt that increased numbers of surgically curable hypertensives can be discovered if each hypertensive patient is given the benefit of a thorough evaluation. In many institutions internists strongly resist surgical intervention in patients with good indications for surgery, claiming that new antihypertensive drugs can adequately lower blood pressure and, therefore, arrest the disease process and eliminate the potential risks of surgery. However, long-term drug therapy involves unpredictable patient compliance as well as drug intolerance Table II), and improvement or cure by surgery with little or no medication is a much more satisfactory end point. Recent advances in the diagnosis of renovascular hypertension and the scoring for surgery make the surgical approach much more palatable and effective. Vaughn et al. in 19733 derived three renin indices to help determine if the hypertensive patient has a surgically correctable lesion. Renin Indices The three renin indices are as follows: (1) Peripheral plasma renin as it relates to the state of the patient’s sodium balance. Since plasma renin
0
5
No. of cases IO 152025303540
EH RAS (Renovoscular) Adrenal Undet. Renal
Etiology Tumors
Pyeloglomerulo RA
Aneurysms
Hydronephrosis Co-arctation the aorta
of
FIGURE 1. Various surgical and nonsurgical entities discovered on hypertensive evaluation. Key: EH, essential hypertension; BH, benign hypertension; AH, accelerated hypertension; MH, malignant hypertension; RAS, renal artery stenosis.
UROLOGY
/ MARCH 1976 !
VOLUME
VII, NUMBER
3
TABLE II. Antihypertensive and their side effects Drugs
Side Effects -___
DIURETICS Sulfonamide (thiazide)
Hypokalemia, hyperuricemia, hyperglycemia
Loop agents Furosemide Ethacrynic
acid
ANTIRENIN Propranolol Clonidine ANTIALDOSTERONE Spironolactone
Triameterene
SYMPATHOLYTIC Guanethidine
Reserpine
Methyldopa
Pargyline (MAO inhibitor) PERIPHERAL VASODILATORS Hydralazine
Minoxidil
drugs
(Same as for thiazides) (Same as for thiazides) Congestive heart failure, bradycardia Xerostomia, drowsiness Lethargy, hyperkalemia, in male decreased potency, breast enlargement and tenderness, masculinization in female Hyperkalemia, diarrhea, nausea, vomiting Postural hypotension, diarrhea, xerostomia, fluid retention, retrograde ejaculation, psychogenic impotence Nasal stuffiness, mental depression, diarrhea, gastric hyperacidity, peptic ulceration Drowsiness, xero, stomia, mood disturbance, fluid retention, drug hepatitis, positive Coombs’ test Hypertensive crisis with tyramine ingestion Tachycardia, palpitations, angina, headache, lupuslike syndrome Hirsuitism
UROLOGY / MARCH 1976 / VOLUME VII, NUMBER 3
activity will vary inversely with sodium excretion, it is imperative to know the status of a patient’s sodium balance to determine if elevated renin values are meaningful (Fig. 2). (2) Differential renal vein renin calculations* (a) V2 - A = 0: Renal venous renin from the uninvolved kidney (V2) minus the aortic renin (A) (essentially, the renin going into each kidney via renal arteries) approximates zero. This is because renin production is suppressed in the uninvolved kidney. If Vz - A > 0, there is evidence of contralateral renin production, indicating the possiblity of bilateral renal involvement. This equation aids in the establishment of laterality for the disease process and adds assurance that the “uninvolved” kidney is not contributing to the patient’s hypertension. (b) VI - AIA > 0.48: Elevated renin secretion from an ischemic kidney produces renin values greater than 0.48 provided there is complete suppression of contralateral renin secretion. A detailed explanation of the renin indices, their derivation and scoring for operability are clearly described in the original article on the subject. 3 A common error that continues to be repeated even in the most recent literature is the significance of renal vein renin ratios. Renal vein renin ratios (renal vein renin ischemic kidney/ renal vein renin uninvolved kidney) are not a particularly accurate method of determining laterality. Those patients with high renal vein renin from the affected kidney will have falsely low ratios (< 1.5) because the high levels of renin recirculating through each kidney have not been taken into account. It is well known that the liver extracts almost 100 per cent of the renin present in the splanchnic blood. 4,5 Blood returning to the heart from the renal veins via the vena cava must also contain renin which continues to be recirculated through both the ischemic and innocent kidney. Thus, only a fraction of the renin of renal venous blood represents true renin secretion, the remainder representing renin recirculation (Fig. 3). The following example illustrates this problem: Example
1
A thirty-three-year-old air controller was discovered to have a blood pressure of 190/136-140 mm. Hg when he volunteered to donate blood. Previous blood pressures had been normal. Six weeks prior to discovery of his hypertension the *Vi, renal vein renin in ischemic kidney; renin in uninvolved kidney; A, aortic renin.
V2,
renal vein
241
1
100
0
200
300
24-Hour Urinary Sodium Excretion FIGURE 2. Renin normogram. Normal renin secretion {shaded area) includes wide range of values that vary inversely with sodium excretion. When sodium excretion is low (< 100 mEq. IL.), renin values are elevated. This represents homeostatic mechanism of renin-angiotensin-aldosterone system to maintain electrolyte balance. Renin values may be accurately interpreted only in light of known concomitant sodium excretion. patient suffered
the sudden onset of severe right flank pain which slowly subsided over a period of three days. Hypertensive evaluation three months after this episode revealed evidence of multiple renal infarcts and an aneurysm of the right renal artery. The patient’s renin values, using the described indices, were as follows: inferior vena cava, I5 ng. per milliliter per hour (peripheral renin); right renal vein, 24 ng. ; left renal vein, 18 ng. (normal peripheral renin 0.4 to 4.5 ng.).
FIGURE 3. Renin extracted from splanchnic blood by liver. Therefwe, hepatic vein blood entering vena cava is renin free. Renin produced by ischemic left kidney enters vena cava and is subsequently pumped by heart into systemic circulation. Consequently, renal vein renin determinations represent active renin secretion by ischemic kidney plus renin which is constantly present in systemic circulation. By subtracting systemic circulating renin from renal vein renin (V-AIA) one arrives atJigure representing active renin secretion by ischemic kidney.
(innocent) kidney, the patient subsequently underwent a right nephrectomy and excision of the right renal artery aneurysm. His right kidney was found to be markedly scarred secondary to several vascular infarctions. Postoperatively, the patient’s blood pressure returned to normal levels without medication. If our decision to operate had been predicated solely on the renal vein renin ratio, we would not have been able to establish significant laterality since the ratio was less than 1.5. Renal vein renin involved kidney = 2% Renal vein renin uninvolved kidney 18
1.33
Because of marked right laterality and evidence of renin suppression in the contralateral
This false negative exists frequently when there are high levels of “recirculating” renin in the systemic circulation. In those patients who present unacceptable operative risks or in whom surgery is not likely to alter long-term prognosis, medical therapy must be considered. Since secondary hypertension is caused by a series of biologic mechanisms (reninangiotensin-aldosterone system, catecholamine elevation, and so on), there are several pathways in which drugs can either block or enzymes detoxify pressor agents or their precursors. The new antihypertensive drugs now on the market, and others soon to be available, have greatly improved our treatment of hypertensive patients in the nonsurgical category (Table III). A brief example of an
242
UROLOGY
Left V-A=
V-A=0
Right V-A= 24 - 15= 9
9>0.48
24 - 15 F=
18 - 15_ 15
9 G = 0.60
3 15 = 0.20
18 - 15= 3
/ MARCH1976
/ VOLUMEVII,
NUMBER3
TABLE III.
New drugs and their
antihypertensive
.
. .
. *
since the patient’s blood pressure was frequently as high as 250/160 mm. Hg. However, renal vein renins were collected, indicating marked left laterality. Because of age, a reduced creatinine clearance (22 cc. per minute), and lack of clinical symptoms, a nephrectomy was deferred in lieu of intensive medical therapy. The patient has been maintained on propranolol (40 mg. four times a day), clonidine (0.2 mg. three times a day), and furosemide (40 mg. daily). Blood pressure has been in the 160-170/80-90 mm. Hg range for the past year. Thus medical therapy becomes an important alternative when the patient’s over-all status precludes surgery. 6-8 With each passing year, urologists are becoming more involved with the basic mechanisms of hypertension and renal disease and their attendant sequelae. Urologists can now feel secure in treating the essential hypertensive patient because of the excellent medical modalities available. Recent schematization of the medical management of essential hypertension has helped to eliminate the problem of selecting the proper antihypertensive drug(s). g Thus, it may not be inappropriate to predict that within the next decade urologists may be called on to treat both the medical and surgical aspects of renal disease, thereby achieving a unified approach to such problems.
. .
. .
. .
111 East 210th Street New York, New York 10467
mechanisms Dose
Mechanisms
(Mg. per Day)
RENIN SUPPRESSORS
40- 160 0.3-0.6
Propranolol Clonidine ANGIOTENSIN ANTAGONIST
Saralasin (1-Sarcosine, Angiotensin II)*
8-Alanine,
ALDOSTERONE BLOCKERS
50-200 200-300
Spironolactone Triamterene SYMPATHOLYTIC DRUGS
15-450 40-80 50-75
Bethanidinet Debrisoquinet Pargyline (MAO inhibitor) PERIPHERAL VASODILATORS
40-200 8-40 400-800 3-15 75- 100
Hydralazine Minoxidill D&oxide Prazosinf Guancydinet Bupicomide* ALPHA ADRENERGIC BLOCKERS$
20-60 200-300
Phenoxybenzamine Phentolamine BETA ADRENERGIC BLOCKER@
Trasicor* Erladin* Aptine* Visken* Propranolol (see above) Pindolol* Practolol*
References
*Being used in clinical investigation. tNot FDA approved, but used clinically in Europe. jAlpha adrenergic receptors produce arteriolar constriction to raise total peripheral resistance and venous constriction to increase venous return to heart.
QBeta adrenergic receptors increase heart rate and myocardial contractility, thus increasing cardiac output.
1. Veterans Administration Cooperative Study Group on
Anti-Hypertensive Agents: Effects of treatment on morbidity in hypertension, J.A.M.A. 202: 1028 (1967);
ibid. 213: 1143 (1970).
2. FOSTER, H., and OATES, J. A.: 3. 4.
elderly patient with renovascular hypertension can adequately illustrate when drug therapy should be used in lieu of surgery. Example
6.
2
A seventy-three-year-old white male presented with a twenty-year history of essential hypertension, easily controlled with diuretics. During the preceding twelve months, his blood pressure steadily began to rise and became unmanageable on antihypertensive medication. Intravenous pyelogram revealed a shrunken left kidney. Renal arteriography was deemed excessively dangerous
UROLOGY /
5.
MARCH 1976 /
VOLUME VII, NUMBER 3
Recognition and management of renovascular hypertension, Hosp. Practice 10: 61 (1975). VAUGHN, E. D., et al.: Renovascular hypertension, Am. J. Med. 55: 402 (1973). HEACOX, R., HARVEY, A. M., and VANDER, A. J.: Hepatic inactivation of renin, Clin. Res. 21: 149 (1967). SCHNEIDER,E. G., et al. : Hepatic clearance of renin in canine experimental models for low-and-high-output heart failure, ibid. 24: 213 (1969). DUSTAN,H. P., MEANEY, T. F., and PAGE, I. H.: Conservative treatment of renovascular hypertension, in Gross, F., Ed.: Anti-Hypertensive Therapy: Principles and Practice, Berlin, Springer-Verlag, 1966, p. 544. GIFFORD, R. W., JR.: Renovascular hypertension, Postgrad. Med. 52: 110 (1972). GIFFORD, R. W., JR., STEWART, B. H., ALFIDI, R. J., and DUSTAN, H. P.: Controlling atherosclerotic renovascular hypertension, Geriatrics 28: 124 (1973). GIFFORD, R. W., JR.: A standard approach to therapy, Postgrad. Med. 56: 20 (1974).
243
HYPERTENSION
Recent Advances in Treatment RICHARD
H. BARD.
M.D.
From the Urology Service, Department of Surgery, Montefiore Hospital and Medical Center, and Albert Einstein College of Medicine, New York, New York
ABSTRACT -In the past five years there have been signijcant advances in the diagnosis and treatment of operative and nonoperative forms of hypertension. Several areas of specijic interest to urologists will be discussed.
Hypertension is probably the most common disease-producing entity in the United States, affecting an estimated 16 per cent of the adult population, Cardiovascular complications of elevated blood pressure include heart disease, cerebral hemorrhage/stroke, renal failure, and blindness. The Veterans Administration Cooperative Study has conclusively demonstrated that even moderate elevations in diastolic blood pressure are associated with significantly shortened life expectancy. A diastolic blood pressure of95 mm. Hg in males age thirty-five to forty-five increases the mortality two and one-half times, and a diastolic pressure of 100 mm. Hg increases the mortality rate five times.’ It is now agreed that a considerable number of hypertensive diseases can be treated surgically (Table I). A conservative estimate indicates that there are more than a million people with renovascular hypertension nationwide who might benefit from surgical intervention. In a recent highly selective series, renovascular hypertensives comprised 15 to 16 per cent,’ although the accepted figure for renovascular hypertensive individuals in the general hypertensive population is 4 per cent. This is of paramount importance to urologists, especially in large metropolitan areas where such cases tend to be clustered. An examPresented at the Seventy-Third Annual Meeting, Section of the American Urological Association, Bermuda, September 21-25, 1975.
UROLOGY
/ MARCH1976
/ VOLUMEVII,
New York Hamilton,
NUMBER3
ple of this is the estimated 74,000 to 102,000 potentially operable hypertensives within a thirty mile radius of New York City. The obvious problem is in clearly identifying this group. The approach to working up the hypertensive patient involves patience, persistence, and clinical intuition. Most hypertensive patients being evaluated by urologists are referred by their internists. However, it should be a routine practice to obtain each new patient’s blood pressure as a screening measure. Any patient having three consecutive blood pressure determinations of 140/90 mm. Hg or greater by the same observer on three separate occasions must be considered to be hypertensive. I. Surgically correctable hypertensive diseases *
TABLE
Disease Essential hypertension Renal parenchymal Renovascular Coarctation of aorta Primary aldosteronism Cushing’s syndrome Pheochromocytoma Other *Estimated hypertensive
Per Cent 89
Population .
.
5 1
840,& tdl,&O,OOO 210,000 to 300,000
0.5 0.2 0.2 0.1
105,000 to 150,ooo 42,000 to 60,000 42,000 to 60,000 . . .
4
that 10 to 15 per cent of U.S. (21 to 30 million individuals).
population
is
239
Hypertensive
Evaluation
The pertinent steps in the hypertensive evaluation are as follows: A. History and physical examination B. Laboratory and diagnostic studies Urinalysis, urine culture Complete blood count, serum electrolytes, creatinine clearance, fasting blood sugar, blood urea nitrogen, serum calcium, phosphorus, uric acid, creatinine, T4, serum cholesterol, and fasting triglycerides Electrocardiogram, chest roentgenogram Twenty-four-hour urine for 17-ketosteroids and 17-OH steroids Urinary catecholamine screening test Rapid sequence intravenous pyelogram Renal scan and/or radioactive renogram (optional in initial evaluation but suggested for complete work-up) C. Results of findings If intravenous pyelogram is abnormal or there is a history of recent onset or rapidly progressive elevations in blood pressure, proceed with: Peripheral blood plasma renin activity (regular diet, upright posture) If peripheral renin is elevated: Renal vein and aortic catheterization for plasma renin activity. Renal arteriogram may be performed at the same time D. If blood pressure elevations are mild, the patient elderly, or if medical status makes surgery dangerous, antihypertensive drugs should be given. If a significant lesion is present, surgery is indicated. If the initial screening studies are negative, it is safe to assume that the patient has only a slim possibility of secondary hypertension and should be treated medically. All other patients should be considered to have potentially curable surgical lesions and should have a renal scan and selective renal arteriogram with concomitant collection of renal vein renins. Of 78 patients thoroughly evaluated for hypertension at the Presbyterian Hospital in New York City from 1967 to 1969, a surprisingly high percentage were found to have surgically correctable conditions who presented with hypertension as their principal physical finding (Fig. 1). These included renal and adrenal tumors, renal artery aneurysm, renal artery stenosis, hydronephrosis, and coarctation of the aorta. In all, a total of 26 of the 78 hypertensive patients underwent some type of surgical procedure (33 per cent). This is not to infer that these statistics apply to the general population. However, one is impressed with
240
the variety of pathologic disorders that present themselves in the disguise of elevated blood pressure. There is little doubt that increased numbers of surgically curable hypertensives can be discovered if each hypertensive patient is given the benefit of a thorough evaluation. In many institutions internists strongly resist surgical intervention in patients with good indications for surgery, claiming that new antihypertensive drugs can adequately lower blood pressure and, therefore, arrest the disease process and eliminate the potential risks of surgery. However, long-term drug therapy involves unpredictable patient compliance as well as drug intolerance Table II), and improvement or cure by surgery with little or no medication is a much more satisfactory end point. Recent advances in the diagnosis of renovascular hypertension and the scoring for surgery make the surgical approach much more palatable and effective. Vaughn et al. in 19733 derived three renin indices to help determine if the hypertensive patient has a surgically correctable lesion. Renin Indices The three renin indices are as follows: (1) Peripheral plasma renin as it relates to the state of the patient’s sodium balance. Since plasma renin
0
5
No. of cases IO 152025303540
EH RAS (Renovoscular) Adrenal Undet. Renal
Etiology Tumors
Pyeloglomerulo RA
Aneurysms
Hydronephrosis Co-arctation the aorta
of
FIGURE 1. Various surgical and nonsurgical entities discovered on hypertensive evaluation. Key: EH, essential hypertension; BH, benign hypertension; AH, accelerated hypertension; MH, malignant hypertension; RAS, renal artery stenosis.
UROLOGY
/ MARCH 1976 !
VOLUME
VII, NUMBER
3
TABLE II. Antihypertensive and their side effects Drugs
Side Effects -___
DIURETICS Sulfonamide (thiazide)
Hypokalemia, hyperuricemia, hyperglycemia
Loop agents Furosemide Ethacrynic
acid
ANTIRENIN Propranolol Clonidine ANTIALDOSTERONE Spironolactone
Triameterene
SYMPATHOLYTIC Guanethidine
Reserpine
Methyldopa
Pargyline (MAO inhibitor) PERIPHERAL VASODILATORS Hydralazine
Minoxidil
drugs
(Same as for thiazides) (Same as for thiazides) Congestive heart failure, bradycardia Xerostomia, drowsiness Lethargy, hyperkalemia, in male decreased potency, breast enlargement and tenderness, masculinization in female Hyperkalemia, diarrhea, nausea, vomiting Postural hypotension, diarrhea, xerostomia, fluid retention, retrograde ejaculation, psychogenic impotence Nasal stuffiness, mental depression, diarrhea, gastric hyperacidity, peptic ulceration Drowsiness, xero, stomia, mood disturbance, fluid retention, drug hepatitis, positive Coombs’ test Hypertensive crisis with tyramine ingestion Tachycardia, palpitations, angina, headache, lupuslike syndrome Hirsuitism
UROLOGY / MARCH 1976 / VOLUME VII, NUMBER 3
activity will vary inversely with sodium excretion, it is imperative to know the status of a patient’s sodium balance to determine if elevated renin values are meaningful (Fig. 2). (2) Differential renal vein renin calculations* (a) V2 - A = 0: Renal venous renin from the uninvolved kidney (V2) minus the aortic renin (A) (essentially, the renin going into each kidney via renal arteries) approximates zero. This is because renin production is suppressed in the uninvolved kidney. If Vz - A > 0, there is evidence of contralateral renin production, indicating the possiblity of bilateral renal involvement. This equation aids in the establishment of laterality for the disease process and adds assurance that the “uninvolved” kidney is not contributing to the patient’s hypertension. (b) VI - AIA > 0.48: Elevated renin secretion from an ischemic kidney produces renin values greater than 0.48 provided there is complete suppression of contralateral renin secretion. A detailed explanation of the renin indices, their derivation and scoring for operability are clearly described in the original article on the subject. 3 A common error that continues to be repeated even in the most recent literature is the significance of renal vein renin ratios. Renal vein renin ratios (renal vein renin ischemic kidney/ renal vein renin uninvolved kidney) are not a particularly accurate method of determining laterality. Those patients with high renal vein renin from the affected kidney will have falsely low ratios (< 1.5) because the high levels of renin recirculating through each kidney have not been taken into account. It is well known that the liver extracts almost 100 per cent of the renin present in the splanchnic blood. 4,5 Blood returning to the heart from the renal veins via the vena cava must also contain renin which continues to be recirculated through both the ischemic and innocent kidney. Thus, only a fraction of the renin of renal venous blood represents true renin secretion, the remainder representing renin recirculation (Fig. 3). The following example illustrates this problem: Example
1
A thirty-three-year-old air controller was discovered to have a blood pressure of 190/136-140 mm. Hg when he volunteered to donate blood. Previous blood pressures had been normal. Six weeks prior to discovery of his hypertension the *Vi, renal vein renin in ischemic kidney; renin in uninvolved kidney; A, aortic renin.
V2,
renal vein
241
1
100
0
200
300
24-Hour Urinary Sodium Excretion FIGURE 2. Renin normogram. Normal renin secretion {shaded area) includes wide range of values that vary inversely with sodium excretion. When sodium excretion is low (< 100 mEq. IL.), renin values are elevated. This represents homeostatic mechanism of renin-angiotensin-aldosterone system to maintain electrolyte balance. Renin values may be accurately interpreted only in light of known concomitant sodium excretion. patient suffered
the sudden onset of severe right flank pain which slowly subsided over a period of three days. Hypertensive evaluation three months after this episode revealed evidence of multiple renal infarcts and an aneurysm of the right renal artery. The patient’s renin values, using the described indices, were as follows: inferior vena cava, I5 ng. per milliliter per hour (peripheral renin); right renal vein, 24 ng. ; left renal vein, 18 ng. (normal peripheral renin 0.4 to 4.5 ng.).
FIGURE 3. Renin extracted from splanchnic blood by liver. Therefwe, hepatic vein blood entering vena cava is renin free. Renin produced by ischemic left kidney enters vena cava and is subsequently pumped by heart into systemic circulation. Consequently, renal vein renin determinations represent active renin secretion by ischemic kidney plus renin which is constantly present in systemic circulation. By subtracting systemic circulating renin from renal vein renin (V-AIA) one arrives atJigure representing active renin secretion by ischemic kidney.
(innocent) kidney, the patient subsequently underwent a right nephrectomy and excision of the right renal artery aneurysm. His right kidney was found to be markedly scarred secondary to several vascular infarctions. Postoperatively, the patient’s blood pressure returned to normal levels without medication. If our decision to operate had been predicated solely on the renal vein renin ratio, we would not have been able to establish significant laterality since the ratio was less than 1.5. Renal vein renin involved kidney = 2% Renal vein renin uninvolved kidney 18
1.33
Because of marked right laterality and evidence of renin suppression in the contralateral
This false negative exists frequently when there are high levels of “recirculating” renin in the systemic circulation. In those patients who present unacceptable operative risks or in whom surgery is not likely to alter long-term prognosis, medical therapy must be considered. Since secondary hypertension is caused by a series of biologic mechanisms (reninangiotensin-aldosterone system, catecholamine elevation, and so on), there are several pathways in which drugs can either block or enzymes detoxify pressor agents or their precursors. The new antihypertensive drugs now on the market, and others soon to be available, have greatly improved our treatment of hypertensive patients in the nonsurgical category (Table III). A brief example of an
242
UROLOGY
Left V-A=
V-A=0
Right V-A= 24 - 15= 9
9>0.48
24 - 15 F=
18 - 15_ 15
9 G = 0.60
3 15 = 0.20
18 - 15= 3
/ MARCH1976
/ VOLUMEVII,
NUMBER3
TABLE III.
New drugs and their
antihypertensive
.
. .
. *
since the patient’s blood pressure was frequently as high as 250/160 mm. Hg. However, renal vein renins were collected, indicating marked left laterality. Because of age, a reduced creatinine clearance (22 cc. per minute), and lack of clinical symptoms, a nephrectomy was deferred in lieu of intensive medical therapy. The patient has been maintained on propranolol (40 mg. four times a day), clonidine (0.2 mg. three times a day), and furosemide (40 mg. daily). Blood pressure has been in the 160-170/80-90 mm. Hg range for the past year. Thus medical therapy becomes an important alternative when the patient’s over-all status precludes surgery. 6-8 With each passing year, urologists are becoming more involved with the basic mechanisms of hypertension and renal disease and their attendant sequelae. Urologists can now feel secure in treating the essential hypertensive patient because of the excellent medical modalities available. Recent schematization of the medical management of essential hypertension has helped to eliminate the problem of selecting the proper antihypertensive drug(s). g Thus, it may not be inappropriate to predict that within the next decade urologists may be called on to treat both the medical and surgical aspects of renal disease, thereby achieving a unified approach to such problems.
. .
. .
. .
111 East 210th Street New York, New York 10467
mechanisms Dose
Mechanisms
(Mg. per Day)
RENIN SUPPRESSORS
40- 160 0.3-0.6
Propranolol Clonidine ANGIOTENSIN ANTAGONIST
Saralasin (1-Sarcosine, Angiotensin II)*
8-Alanine,
ALDOSTERONE BLOCKERS
50-200 200-300
Spironolactone Triamterene SYMPATHOLYTIC DRUGS
15-450 40-80 50-75
Bethanidinet Debrisoquinet Pargyline (MAO inhibitor) PERIPHERAL VASODILATORS
40-200 8-40 400-800 3-15 75- 100
Hydralazine Minoxidill D&oxide Prazosinf Guancydinet Bupicomide* ALPHA ADRENERGIC BLOCKERS$
20-60 200-300
Phenoxybenzamine Phentolamine BETA ADRENERGIC BLOCKER@
Trasicor* Erladin* Aptine* Visken* Propranolol (see above) Pindolol* Practolol*
References
*Being used in clinical investigation. tNot FDA approved, but used clinically in Europe. jAlpha adrenergic receptors produce arteriolar constriction to raise total peripheral resistance and venous constriction to increase venous return to heart.
QBeta adrenergic receptors increase heart rate and myocardial contractility, thus increasing cardiac output.
1. Veterans Administration Cooperative Study Group on
Anti-Hypertensive Agents: Effects of treatment on morbidity in hypertension, J.A.M.A. 202: 1028 (1967);
ibid. 213: 1143 (1970).
2. FOSTER, H., and OATES, J. A.: 3. 4.
elderly patient with renovascular hypertension can adequately illustrate when drug therapy should be used in lieu of surgery. Example
6.
2
A seventy-three-year-old white male presented with a twenty-year history of essential hypertension, easily controlled with diuretics. During the preceding twelve months, his blood pressure steadily began to rise and became unmanageable on antihypertensive medication. Intravenous pyelogram revealed a shrunken left kidney. Renal arteriography was deemed excessively dangerous
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VOLUME VII, NUMBER 3
Recognition and management of renovascular hypertension, Hosp. Practice 10: 61 (1975). VAUGHN, E. D., et al.: Renovascular hypertension, Am. J. Med. 55: 402 (1973). HEACOX, R., HARVEY, A. M., and VANDER, A. J.: Hepatic inactivation of renin, Clin. Res. 21: 149 (1967). SCHNEIDER,E. G., et al. : Hepatic clearance of renin in canine experimental models for low-and-high-output heart failure, ibid. 24: 213 (1969). DUSTAN,H. P., MEANEY, T. F., and PAGE, I. H.: Conservative treatment of renovascular hypertension, in Gross, F., Ed.: Anti-Hypertensive Therapy: Principles and Practice, Berlin, Springer-Verlag, 1966, p. 544. GIFFORD, R. W., JR.: Renovascular hypertension, Postgrad. Med. 52: 110 (1972). GIFFORD, R. W., JR., STEWART, B. H., ALFIDI, R. J., and DUSTAN, H. P.: Controlling atherosclerotic renovascular hypertension, Geriatrics 28: 124 (1973). GIFFORD, R. W., JR.: A standard approach to therapy, Postgrad. Med. 56: 20 (1974).
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