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Effects of Bilateral Nephrectomy on Blood Pressure and Renin Activity
Vol. 107, May Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright © 1972 by The Williams & Wilkins Co.
EFFECTS OF BILATERAL NEPHRECTOMY ON BLOOD PRESSURE AND RENIN ACTIVITY J. W. MOSTERT, R. H. MOORE
AND
G. P. MURPHY*
From the Roswell Park Memorial Institute, New York State Department of Health and the State University of New York, Buffalo, New York
Peripheral vascular tone may be subject to rapid regional and general adjustments by both neural and hormonal biochemicals, especially the catecholamines and the renin angiotensin system. However, bilateral nephrectomy performed prior to renal allotransplantation can reduce blood pressure associated with plasma renin levels which are inappropriately high. 1 \.Ye have observed that mild hypertension seemed to be corrected by hemodialysis for variable periods of 12 to 24 hours. However, in some patients bilateral nephrectomy frequently produced normal blood pressure for an observed period of 1 year. Herein we report on the relationships between plasma renin and blood pressure. Studies were carried out on 25 patients in end-stage renal failure with creatinine clearances of less than 5 ml. per minute (table 1). Studies were carried out before and after bilateral nephrectomy and after renal allotransplantation. MATERIALS AND METHODS
The mean age of patients was 37.8 years, ranging from 20 to 62 years. Hemodynamic studies with right heart catheterization, using a small catheter "floated" into the right ventricle after percutaneous insertion into an internal jugular vein, were carried out before and after bilateral nephrectomy and after renal allotransplantation. 2 Venous plasma renin activity was measured by a modification of the method of Boucher and associates. 3 This technique measures renin-like activity as well as renin. Results are therefore different from radio-immunoassay which is usually negative in the anephric state. Plasma dialyzed for 24 hours in distilled water, incubated for 1 hour and compared with a known standard of angiotensin in nephrectomized rats gives a Accepted for publication June 11, 1971. Supported in part by the National Institutes of Health Grant FR05648-05. * Requests for reprints: 666 Elm Street, Buffalo, New York 14206. 1 Wilkinson, R., Scott, D. F., Uldall, P.R., Kerr, D. N. S. and Swinney, J.: Plasma renin and exchangeable sodium in the hypertension of chronic renal failure. The effect of bilateral nephrectomy. Quart. J. Med., 39: 377, 1970. 2 Mostert, J. W., Evers, J. L., Hobika, G. H., Moore, R.H., Kenny, G. M. and Murphy, G. P.: The haemodynamic response to chronic renal failure as studied in the alil-0-taemic state. Brit. J. Anaesth., 42: 397, 1970. 3 Boucher, R., Veyrat, R., de Champlain, J. and Genest, J.: New procedures for measurement of human plasma angiotensin and renin activity levels. Canad. Med. Ass. J., 90: 194, 1964.
TABLE
l. Pre-treatment diagnosis of 25 patients
Chronic glomerulonephritis. . . . Chronic pyelonephritis... Chronic pyelonephritis with vesicoureteral reflux. Polycystic kidneys. . Diabetic nephropftthy. Familial nephritis .. .
14 3 4 2
25
normal value of approximately 466 ng. per 100 ml. per hour. Blood specimens were taken in the morning prior to patient ambulation. The criteria of hypertension as enumerated by Pickering were simplified for statistical purposes. 4 The presence or absence of hypertension was recorded as a mean arterial pressure greater or less than 110 mm. Hg respectively. With this criterion, 18 of the 25 patients were initially classified as hypertensive. Blood volume was measured with a 125-radioiodinated human serum albumin and the volemetron. Predicted blood volumes were derived from a nomogram described previously. 5 Angiotensin infusion tests were done preoperatively in 3 of our most severely hypertensive patients. 6 Six mµg. angiotensin per minute per kg. were administered intravenously with the aid of a constant infusion pump. Mean arterial pressure was computed electronically during radial artery catheterization performed for hemodynamic assessments, and in 11 additional post-allotranspla1itation studies by the addition of one-third of the pulse pressure to the diastolic pressure as measured in the indirect clinical fashion. RESULTS
There was no statistical correlation between mean plasma renin activity and other circulatory indices listed in tables 2 and 3, before or after bilateral nephrectomy and renal transplantation. The correlation coefficients varied in the random range of minus 0.32 to plus 0.37. Exceptions to this finding are presented in the case reports. Our most striking finding was a highly significant decrease of mean blood pressure following bilateral nephrectomy and a highly significant persistence of 4 Pickering, G.: High Blood Pressure, 2nd ed. London: J. & A. Churchill, Ltd., pp.138 and 629, 1968. 5 Mostert, J. W., Albano, P. C., Seniff, A. and Moore, R. H.: Blood volume in patients with cancer. Anesth. Analg., 47: 463, 1968. 6 Kaplan, N. M. and Silah, J. G. : The angiotensininfusion test. A new approach to the differential diagnosis of renovascular hypertension. New Engl. J. Med., 271: 536, 1964.
677
678
MOSTERT, MOORE AND :\!URPHY TABLE
2. Statistical summary of hemodynamic studies in 25 patients Post-Bilateral Nephrectomy Pretreatment Mean± Standard Error (25 studies)
Renin (ng./100 ml./hr.) Mean arterial pressure (mm. Hg) Cardiac index (L/min./m2 .) Total peripheral resistance (dynes per sec. per cm.-5) Heart rate Right ventricular systolic pressure (mm. Hg) Right ventricular end-diastolic pressure (mm. Hg)
745 130 4.36 1,333
± ± ± ±
73.9 4.25 0. 17 71.5
After 6 Weeks Mean± Standard Error (20 studies) 408. 4 100 4.32 1,241
± ± ± ±
65. 6* 5.00t 0.14 61.1
Post-Allotransplantation
After 6 Mon th s Mean± Standard Error (15 studies)
After 6 Weeks Mean± Standard Error (8 studies)
After 6 Months Mean± Standard Error (11 studies)
4041 106. 07 ± 6. 47t 3.46 ± 0.33 1,423 ± 150.1
607. 4 ± 64. 5* 110. 6 ± 3. 95t 3.80 ± 0.23 1,204 ± 110.9
1.164 ± 247. 44* 104. 73 ± 4. 37t 3. 50 ± 0.21 1,434 ± 131. 8
79.50 ± 6.46 41.12 ± 5.02
86.4 ± 3.41 37.4 ± 2.24
83.35 ± 3.04 36.25 ± 2.55
84.80 ± 2.31 36.40 ± 2.99
8.3 ± 1.66
6.37 ± 0.56
6.08±0.68
10.66
±
2. 15
71. 73 ± 4. 73 37.45 ± 3.38 7. 76
±
1.08
* Mean of 5 studies. 1 Single study. i Mean of 25 studies. TABLE
3. Statistical summary of fluid ancl electrolyte balance Post-Bilateral Nephrectomy
Pretreatment Mean± Standard Error (39 studies)
Blood volume (ml.) Predicted blood volume (ml.) Hcmatocrit (%) Arterial pH
4,097 ± 172 4,306 ± 134 25.6 ± 1.20 7.36 ± 0.007
After 6 Weeks Means± Standard Errors (20 studies)
After 6 Months Means± Standard Errors (17 studies)
Post-Allo transplantation After 6 Weeks Standard Errors (8 studies)
After 6 Months Means± Standard Errors ( 11 studies)
l\!Ieans
±
4,550 ± 192.8 3,788 ± 131
4,493 ± 220 4,172 ± 284
4,412 ± 552. 1 4,329 ± 337
4,011 ± 333.8 4,585 ± 235
22.24 ± 1. 6 7.336 ± 0.01
19.7-l ± 0.62 7.339 ± 0.01
21.28 ± 2. 14 7.352 ± 0.017
29.93 ± 1.81 7.364 ± 0.006
normotension at 6 weeks and 6 months after bilateral nephrectomy (table 2). The blood pressure seemed to remain normal during the same periods of time following successful allotransplantation. All these changes from the initial mean arterial pressure were highly significant (p less than 0.001). Cardiac output was elevated initially but had returned to normal 6 months after allotransplantation, and this was accompanied by a significant improvement of anemia (table 3). Total peripheral resistance tended to rise during the same period and heart rate slowed toward a more normal figure. Pressures in the right ventricle showed no significant changes although in individual cases right ventricular systolic pressure was a sensitive indicator of circulatory congestion. There was initially a significantly constricted blood volume which correlated with increases in blood pressure (correlation coefficient plus 0.65). After allotransplantation this situation was reversed; a slight hypervolemm then accompanied persistently normal blood pressure. For each of our 3 most severely hypertensive patients angiotensin infusions increased diastolic pressure more than 30 mm. Hg. Selected case reports illustrate isolated increases of plasma renin activity, low blood volumes and malignant hypertension corrected by bilateral nephrectomy performed as preparation for renal allotransplantation. CASE REPORTS
Case 1. R.H.B., a 45-year-old man, was in endstage renal failure and was managed on twice-weekly
hemodialysis. He had a constricted plasma volume and blood pressure 291/145, mean 183 mm. Hg, cardiac output 7.47 L per minute, hematocrit 19 per cent and plasma renin activity 1,076 ng. per 100 ml. per hour. Six weeks after bilateral nephrectomy plasma renin activity was 262 ng. per 100 ml. per hour. At this time blood pressure was 140/80, mean 100 mm. Hg, cardiac output 8.3 L per minute and hematocrit 18 per cent. Right heart pressures showed great improvement in initially severe circulatory congestion. Cadaver allotransplantation was subsequently carried out. Testing 6 weeks and 6 months after allotransplantation showed essentially unchanged hemodynamic values. Six months after grafting renin activity was 952 ng. per 100 ml. per hour. This case demonstrates elevated plasma renin activity associated with symptomatology of chronic renal failure and regression of both after bilateral nephrectomy. Remarkably, plasma renin activity was still measurable after bilateral nephrectomy and a high activity was restored 6 months after allotransplantation. Case 2. S.G., a 27-year-old patient, was maintained on twice-weekly dialysis. This patient had a plasma volume 400 ml. less than the predicted ideal value, blood pressure 184/96, mean 138 mm. Hg, cardiac output 3.64 L per minute per m 2 body surface area, total peripheral resistance 2,260 dynes per second per cm.~ 5 and plasma renin activity 467 ng. per 100 ml. per hour. Three weeks after bilateral nephrectomy plasma volume was normal, blood
679
EFFECTS OF BILATERAL NEPHRECTOMY
pressure 168/60, mean 84 mm. Hg, cardiac output 6.1 L per minute per m 2 body surface area and total peripheral resistance 1,160 dynes per second per cm.- 5 • In this case we note regression in symptomatology and a movement of plasma renin activity toward normal after bilateral nephrectomy. However, it is remarkable that renin activity was measurable at all in the anephric state. COMME_:,,fTS
This study provides data in support of the clinical impression that normal blood pressure is restored after bilateral nephrectomy in patients with endstage renal disease. It suggests an important species difference between man and dog, since it fails to provide evidence of renoprival hypertension as seen in the dog. 7 This finding may cast some doubt on the role in all species of vasopressor substances of central origin in the pathogenesis of borderline hypertension in terminal renal failure. 8 These observations favor the concept that renal ischemia, unlike the primary mechanisms of essential hypertension, 9 is frequently the cause of borderline hypertension in patients with chronic renal failure and may be analogous to renovascular hypertension resulting from advanced stenosing lesions of the renal arteries. 10 • 11 In our patients increased plasma renin activity was difficult to demonstrate except in those with unusually low blood volume, low plasma osmolality and malignant hypertension. This finding is consistent with the experience of others. 12 • 13 However, the pathogenetic significance of renin or similar substances originating in the kidney in hypertension of uremic patients is suggested by the restoration of normal blood pressure after bilateral nephrectomy, It can be argued that as hypertension develops the baroreceptors reset at a higher 7 Kolff, W. J. and Page, I. H.: Persistence of experimental renal hypertension after total nephrectomy in dogs. Amer. J. Physiol., 182: 531, 195,'i. 8 Taylor, R. D. and Page, I. H.: Vasoprcssor substance (cerebrotonin) of central origin. Amer. J. Physiol., 183: 12, 1955. 9 Onesti, G.: The hemodynamics of hypertension. In: Cardiovascular Clinics. Edited by A. N. Brest. Philadelphia: F. A. Davis Co., vol. 1, 1969. 10 Renal origin of malignant hypertension. (editorial.) J.A.M.A., 213:1889, 1970. 11 Onesti. G., Swartz, C., Ramirez, 0. and Brest, A. N.: Bilateral nephrectomy for control of hypertension in uremia. Trans. Amer. Soc. Artif. Intern. Organs, 14:361, 1968. 12 Julius, S., Pascual, A. V., Reilly, K. and London, IL: Abnormalities of plasma volume in borderline hypertension. A1ch. Intern. Med., 127: 116, 1971. 13 Credi tor, M. C. and Loschky, U. K.: Plasma renin activity in hypertension. Amer. J. Med., 43: 371, 1967.
level and renin secretion returns toward normal because renal ischemia is corrected by increased perfusion pressure. 14 Malignant hypertension may then result from breakdown of baroreceptor feedback when a critical high level of blood pressure is attained. The initially observed constriction of blood volume is probably secondary to physiologically significant although borderline hypertension, which is a feature of end-stage renal failure. 12 It also means that the true hematocrit was less than the initially observed mean of 25.6 per cent since large-vessel hematocrit is increased in proportion to constriction of plasma volume. 12 The finding of near normal plasma (renin-like) activity in 6 anephric patients is new. Extrarenal sources of renin are suggested by Peart. 15 The elevated cardiac outputs of our patients are in response to their severe anemia which most likely also accounts for the near normal peripheral resistance. 16 Thus, bilateral nephrectomy has a definite effect on pressor responses and hypertension in the uremic patient. The effects and responses do not entirely relate on a causal basis to renin elevations. SUMMARY
Significant borderline hypertension was found prior to bilateral nephrectomy performed as preparation for allotransplantation in 25 patients with end-stage renal disease. This was accompanied constriction of plasma volume and elevation of cardiac output due to severe anemia. Bilateral nephrectomy abolished the elevated blood pressure and constricted plasma volume, and allotransplantation restored more normal hematocrit, heart rate and cardiac output. Two selected case reports illustrate increased plasma renin activity in patients with low plasma volumes and malignant hypertension. Although normal renin activity and normal peripheral vascular reactivity to angiotensin infusions usually were found prior to bilateral nephrectomy, renin is still the most likely single pathogenetic factor in the borderline hypertension of chronic renal failure. Increased blood pressure may correct renal ischemia and thus normalize activity of the renin angioteusin system transiently, until baroreceptor feedback is ultimately overwhelmed by uncontrolled hypertension. Other substances, presently ill-defined but related to renm, may also be operative. "McCubbin, J. W., Green, J. H. and Page, I. H. · Baroceptor function in chronic renal hypertension. Circ. Res., 4: 205, 19,56. 15 Peart, W. S.: The renin-angiotensin system. . Pharmacol. Rev., 17: 143, 196/'i. 16 Duke, M. and Adelmann, W. H.: The hemodynarnic response to chronic anemia. Circulation, 29: 503, 1969.
THE JOURNAL OF UROLOGY
Copyright © 1972 by The Williams & Wilkins Co.
EFFECTS OF BILATERAL NEPHRECTOMY ON BLOOD PRESSURE AND RENIN ACTIVITY J. W. MOSTERT, R. H. MOORE
AND
G. P. MURPHY*
From the Roswell Park Memorial Institute, New York State Department of Health and the State University of New York, Buffalo, New York
Peripheral vascular tone may be subject to rapid regional and general adjustments by both neural and hormonal biochemicals, especially the catecholamines and the renin angiotensin system. However, bilateral nephrectomy performed prior to renal allotransplantation can reduce blood pressure associated with plasma renin levels which are inappropriately high. 1 \.Ye have observed that mild hypertension seemed to be corrected by hemodialysis for variable periods of 12 to 24 hours. However, in some patients bilateral nephrectomy frequently produced normal blood pressure for an observed period of 1 year. Herein we report on the relationships between plasma renin and blood pressure. Studies were carried out on 25 patients in end-stage renal failure with creatinine clearances of less than 5 ml. per minute (table 1). Studies were carried out before and after bilateral nephrectomy and after renal allotransplantation. MATERIALS AND METHODS
The mean age of patients was 37.8 years, ranging from 20 to 62 years. Hemodynamic studies with right heart catheterization, using a small catheter "floated" into the right ventricle after percutaneous insertion into an internal jugular vein, were carried out before and after bilateral nephrectomy and after renal allotransplantation. 2 Venous plasma renin activity was measured by a modification of the method of Boucher and associates. 3 This technique measures renin-like activity as well as renin. Results are therefore different from radio-immunoassay which is usually negative in the anephric state. Plasma dialyzed for 24 hours in distilled water, incubated for 1 hour and compared with a known standard of angiotensin in nephrectomized rats gives a Accepted for publication June 11, 1971. Supported in part by the National Institutes of Health Grant FR05648-05. * Requests for reprints: 666 Elm Street, Buffalo, New York 14206. 1 Wilkinson, R., Scott, D. F., Uldall, P.R., Kerr, D. N. S. and Swinney, J.: Plasma renin and exchangeable sodium in the hypertension of chronic renal failure. The effect of bilateral nephrectomy. Quart. J. Med., 39: 377, 1970. 2 Mostert, J. W., Evers, J. L., Hobika, G. H., Moore, R.H., Kenny, G. M. and Murphy, G. P.: The haemodynamic response to chronic renal failure as studied in the alil-0-taemic state. Brit. J. Anaesth., 42: 397, 1970. 3 Boucher, R., Veyrat, R., de Champlain, J. and Genest, J.: New procedures for measurement of human plasma angiotensin and renin activity levels. Canad. Med. Ass. J., 90: 194, 1964.
TABLE
l. Pre-treatment diagnosis of 25 patients
Chronic glomerulonephritis. . . . Chronic pyelonephritis... Chronic pyelonephritis with vesicoureteral reflux. Polycystic kidneys. . Diabetic nephropftthy. Familial nephritis .. .
14 3 4 2
25
normal value of approximately 466 ng. per 100 ml. per hour. Blood specimens were taken in the morning prior to patient ambulation. The criteria of hypertension as enumerated by Pickering were simplified for statistical purposes. 4 The presence or absence of hypertension was recorded as a mean arterial pressure greater or less than 110 mm. Hg respectively. With this criterion, 18 of the 25 patients were initially classified as hypertensive. Blood volume was measured with a 125-radioiodinated human serum albumin and the volemetron. Predicted blood volumes were derived from a nomogram described previously. 5 Angiotensin infusion tests were done preoperatively in 3 of our most severely hypertensive patients. 6 Six mµg. angiotensin per minute per kg. were administered intravenously with the aid of a constant infusion pump. Mean arterial pressure was computed electronically during radial artery catheterization performed for hemodynamic assessments, and in 11 additional post-allotranspla1itation studies by the addition of one-third of the pulse pressure to the diastolic pressure as measured in the indirect clinical fashion. RESULTS
There was no statistical correlation between mean plasma renin activity and other circulatory indices listed in tables 2 and 3, before or after bilateral nephrectomy and renal transplantation. The correlation coefficients varied in the random range of minus 0.32 to plus 0.37. Exceptions to this finding are presented in the case reports. Our most striking finding was a highly significant decrease of mean blood pressure following bilateral nephrectomy and a highly significant persistence of 4 Pickering, G.: High Blood Pressure, 2nd ed. London: J. & A. Churchill, Ltd., pp.138 and 629, 1968. 5 Mostert, J. W., Albano, P. C., Seniff, A. and Moore, R. H.: Blood volume in patients with cancer. Anesth. Analg., 47: 463, 1968. 6 Kaplan, N. M. and Silah, J. G. : The angiotensininfusion test. A new approach to the differential diagnosis of renovascular hypertension. New Engl. J. Med., 271: 536, 1964.
677
678
MOSTERT, MOORE AND :\!URPHY TABLE
2. Statistical summary of hemodynamic studies in 25 patients Post-Bilateral Nephrectomy Pretreatment Mean± Standard Error (25 studies)
Renin (ng./100 ml./hr.) Mean arterial pressure (mm. Hg) Cardiac index (L/min./m2 .) Total peripheral resistance (dynes per sec. per cm.-5) Heart rate Right ventricular systolic pressure (mm. Hg) Right ventricular end-diastolic pressure (mm. Hg)
745 130 4.36 1,333
± ± ± ±
73.9 4.25 0. 17 71.5
After 6 Weeks Mean± Standard Error (20 studies) 408. 4 100 4.32 1,241
± ± ± ±
65. 6* 5.00t 0.14 61.1
Post-Allotransplantation
After 6 Mon th s Mean± Standard Error (15 studies)
After 6 Weeks Mean± Standard Error (8 studies)
After 6 Months Mean± Standard Error (11 studies)
4041 106. 07 ± 6. 47t 3.46 ± 0.33 1,423 ± 150.1
607. 4 ± 64. 5* 110. 6 ± 3. 95t 3.80 ± 0.23 1,204 ± 110.9
1.164 ± 247. 44* 104. 73 ± 4. 37t 3. 50 ± 0.21 1,434 ± 131. 8
79.50 ± 6.46 41.12 ± 5.02
86.4 ± 3.41 37.4 ± 2.24
83.35 ± 3.04 36.25 ± 2.55
84.80 ± 2.31 36.40 ± 2.99
8.3 ± 1.66
6.37 ± 0.56
6.08±0.68
10.66
±
2. 15
71. 73 ± 4. 73 37.45 ± 3.38 7. 76
±
1.08
* Mean of 5 studies. 1 Single study. i Mean of 25 studies. TABLE
3. Statistical summary of fluid ancl electrolyte balance Post-Bilateral Nephrectomy
Pretreatment Mean± Standard Error (39 studies)
Blood volume (ml.) Predicted blood volume (ml.) Hcmatocrit (%) Arterial pH
4,097 ± 172 4,306 ± 134 25.6 ± 1.20 7.36 ± 0.007
After 6 Weeks Means± Standard Errors (20 studies)
After 6 Months Means± Standard Errors (17 studies)
Post-Allo transplantation After 6 Weeks Standard Errors (8 studies)
After 6 Months Means± Standard Errors ( 11 studies)
l\!Ieans
±
4,550 ± 192.8 3,788 ± 131
4,493 ± 220 4,172 ± 284
4,412 ± 552. 1 4,329 ± 337
4,011 ± 333.8 4,585 ± 235
22.24 ± 1. 6 7.336 ± 0.01
19.7-l ± 0.62 7.339 ± 0.01
21.28 ± 2. 14 7.352 ± 0.017
29.93 ± 1.81 7.364 ± 0.006
normotension at 6 weeks and 6 months after bilateral nephrectomy (table 2). The blood pressure seemed to remain normal during the same periods of time following successful allotransplantation. All these changes from the initial mean arterial pressure were highly significant (p less than 0.001). Cardiac output was elevated initially but had returned to normal 6 months after allotransplantation, and this was accompanied by a significant improvement of anemia (table 3). Total peripheral resistance tended to rise during the same period and heart rate slowed toward a more normal figure. Pressures in the right ventricle showed no significant changes although in individual cases right ventricular systolic pressure was a sensitive indicator of circulatory congestion. There was initially a significantly constricted blood volume which correlated with increases in blood pressure (correlation coefficient plus 0.65). After allotransplantation this situation was reversed; a slight hypervolemm then accompanied persistently normal blood pressure. For each of our 3 most severely hypertensive patients angiotensin infusions increased diastolic pressure more than 30 mm. Hg. Selected case reports illustrate isolated increases of plasma renin activity, low blood volumes and malignant hypertension corrected by bilateral nephrectomy performed as preparation for renal allotransplantation. CASE REPORTS
Case 1. R.H.B., a 45-year-old man, was in endstage renal failure and was managed on twice-weekly
hemodialysis. He had a constricted plasma volume and blood pressure 291/145, mean 183 mm. Hg, cardiac output 7.47 L per minute, hematocrit 19 per cent and plasma renin activity 1,076 ng. per 100 ml. per hour. Six weeks after bilateral nephrectomy plasma renin activity was 262 ng. per 100 ml. per hour. At this time blood pressure was 140/80, mean 100 mm. Hg, cardiac output 8.3 L per minute and hematocrit 18 per cent. Right heart pressures showed great improvement in initially severe circulatory congestion. Cadaver allotransplantation was subsequently carried out. Testing 6 weeks and 6 months after allotransplantation showed essentially unchanged hemodynamic values. Six months after grafting renin activity was 952 ng. per 100 ml. per hour. This case demonstrates elevated plasma renin activity associated with symptomatology of chronic renal failure and regression of both after bilateral nephrectomy. Remarkably, plasma renin activity was still measurable after bilateral nephrectomy and a high activity was restored 6 months after allotransplantation. Case 2. S.G., a 27-year-old patient, was maintained on twice-weekly dialysis. This patient had a plasma volume 400 ml. less than the predicted ideal value, blood pressure 184/96, mean 138 mm. Hg, cardiac output 3.64 L per minute per m 2 body surface area, total peripheral resistance 2,260 dynes per second per cm.~ 5 and plasma renin activity 467 ng. per 100 ml. per hour. Three weeks after bilateral nephrectomy plasma volume was normal, blood
679
EFFECTS OF BILATERAL NEPHRECTOMY
pressure 168/60, mean 84 mm. Hg, cardiac output 6.1 L per minute per m 2 body surface area and total peripheral resistance 1,160 dynes per second per cm.- 5 • In this case we note regression in symptomatology and a movement of plasma renin activity toward normal after bilateral nephrectomy. However, it is remarkable that renin activity was measurable at all in the anephric state. COMME_:,,fTS
This study provides data in support of the clinical impression that normal blood pressure is restored after bilateral nephrectomy in patients with endstage renal disease. It suggests an important species difference between man and dog, since it fails to provide evidence of renoprival hypertension as seen in the dog. 7 This finding may cast some doubt on the role in all species of vasopressor substances of central origin in the pathogenesis of borderline hypertension in terminal renal failure. 8 These observations favor the concept that renal ischemia, unlike the primary mechanisms of essential hypertension, 9 is frequently the cause of borderline hypertension in patients with chronic renal failure and may be analogous to renovascular hypertension resulting from advanced stenosing lesions of the renal arteries. 10 • 11 In our patients increased plasma renin activity was difficult to demonstrate except in those with unusually low blood volume, low plasma osmolality and malignant hypertension. This finding is consistent with the experience of others. 12 • 13 However, the pathogenetic significance of renin or similar substances originating in the kidney in hypertension of uremic patients is suggested by the restoration of normal blood pressure after bilateral nephrectomy, It can be argued that as hypertension develops the baroreceptors reset at a higher 7 Kolff, W. J. and Page, I. H.: Persistence of experimental renal hypertension after total nephrectomy in dogs. Amer. J. Physiol., 182: 531, 195,'i. 8 Taylor, R. D. and Page, I. H.: Vasoprcssor substance (cerebrotonin) of central origin. Amer. J. Physiol., 183: 12, 1955. 9 Onesti, G.: The hemodynamics of hypertension. In: Cardiovascular Clinics. Edited by A. N. Brest. Philadelphia: F. A. Davis Co., vol. 1, 1969. 10 Renal origin of malignant hypertension. (editorial.) J.A.M.A., 213:1889, 1970. 11 Onesti. G., Swartz, C., Ramirez, 0. and Brest, A. N.: Bilateral nephrectomy for control of hypertension in uremia. Trans. Amer. Soc. Artif. Intern. Organs, 14:361, 1968. 12 Julius, S., Pascual, A. V., Reilly, K. and London, IL: Abnormalities of plasma volume in borderline hypertension. A1ch. Intern. Med., 127: 116, 1971. 13 Credi tor, M. C. and Loschky, U. K.: Plasma renin activity in hypertension. Amer. J. Med., 43: 371, 1967.
level and renin secretion returns toward normal because renal ischemia is corrected by increased perfusion pressure. 14 Malignant hypertension may then result from breakdown of baroreceptor feedback when a critical high level of blood pressure is attained. The initially observed constriction of blood volume is probably secondary to physiologically significant although borderline hypertension, which is a feature of end-stage renal failure. 12 It also means that the true hematocrit was less than the initially observed mean of 25.6 per cent since large-vessel hematocrit is increased in proportion to constriction of plasma volume. 12 The finding of near normal plasma (renin-like) activity in 6 anephric patients is new. Extrarenal sources of renin are suggested by Peart. 15 The elevated cardiac outputs of our patients are in response to their severe anemia which most likely also accounts for the near normal peripheral resistance. 16 Thus, bilateral nephrectomy has a definite effect on pressor responses and hypertension in the uremic patient. The effects and responses do not entirely relate on a causal basis to renin elevations. SUMMARY
Significant borderline hypertension was found prior to bilateral nephrectomy performed as preparation for allotransplantation in 25 patients with end-stage renal disease. This was accompanied constriction of plasma volume and elevation of cardiac output due to severe anemia. Bilateral nephrectomy abolished the elevated blood pressure and constricted plasma volume, and allotransplantation restored more normal hematocrit, heart rate and cardiac output. Two selected case reports illustrate increased plasma renin activity in patients with low plasma volumes and malignant hypertension. Although normal renin activity and normal peripheral vascular reactivity to angiotensin infusions usually were found prior to bilateral nephrectomy, renin is still the most likely single pathogenetic factor in the borderline hypertension of chronic renal failure. Increased blood pressure may correct renal ischemia and thus normalize activity of the renin angioteusin system transiently, until baroreceptor feedback is ultimately overwhelmed by uncontrolled hypertension. Other substances, presently ill-defined but related to renm, may also be operative. "McCubbin, J. W., Green, J. H. and Page, I. H. · Baroceptor function in chronic renal hypertension. Circ. Res., 4: 205, 19,56. 15 Peart, W. S.: The renin-angiotensin system. . Pharmacol. Rev., 17: 143, 196/'i. 16 Duke, M. and Adelmann, W. H.: The hemodynarnic response to chronic anemia. Circulation, 29: 503, 1969.