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Renal Function 27 Years after Unilateral Nephrectomy for Related Donor Kidney Transplantation
0022-534 7/88/1404-0810$02.00/0 Vol. 140, October Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright © 1988 by The Williams & Wilkins Co.
RENAL FUNCTION 27 YEARS AFTER UNILATERAL NEPHRECTOMY FOR RELATED DONOR KIDNEY TRANSPLANTATION LAWRENCE L. BOHANNON,* JOHN M. BARRY, DOUGLAS J. NORMAN AND WILLIAM M. BENNETTt From the Renal Transplant Service, Divisions of Nephrology and Urology, The Oregon Health Sciences University, Portland, Oregon
ABSTRACT
Renal function in a living related kidney donor was evaluated 27 years after unilateral nephrectomy. The patient was normotensive and had no significant proteinuria. Creatinine was 0.8 mg. per dl. and creatinine clearance was 88 ml. per minute per 1. 73 m. 2 or 152 per cent of the single kidney pre-nephrectomy value. Tubular function assessed by the ability to lower urinary pH in response to an acid load was normal. Biopsy of the transplanted kidney 18 years after donation was histologically normal. This case represents one of the longest followup evaluations of a living related donor reported to date and it argues against any adverse effects of organ donation on the function of the remaining kidney. (J. Ural., 140: 810-811, 1988) The productive lives of many individuals with end stage renal disease have been extended because a living relative donated a kidney for transplantation. Recipients of living related donor kidneys fare significantly better than their cadaveric recipient counterparts in terms of patient and graft survival, and incidence of complications. Concerns about the long-term consequences of renal donation have recently arisen because of experimental evidence documenting glomerular hyperfiltration with increased intraglomerular pressures as a result of ablation of a renal mass. 1 Indeed, urinary albumin excretion is increased compared to age-matched controls in kidney donors studied 9 to 15 years after donation. 2 Development of renal dysfunction has not been observed and although hypertension develops in some patients its prevalence is not greater than the general population. 3- 5 However, since living related donors tend to be in the third and fourth decades of life, followup periods even as long as 10 to 20 years may be insufficient to observe clinical evidence of decreased renal function. We report a detailed evaluation of a woman who donated a kidney for transplantation 27 years ago. She was the first living, related kidney donor at the Oregon Health Sciences University in October 1959. CASE REPORT
C. C., a 39-year-old white woman, had undergone left donor nephrectomy on October 9, 1959 when she was 12 years old to provide an isograft for her identical twin sister C. W. C. W. had end stage disease secondary to chronic glomerulonephritis. Before nephrectomy C. C. underwent a complete medical evaluation, including an excretory urogram (normal) and a 12-hour creatinine clearance (116 ml. per minute per 1.73 m. 2 ). Prenephrectomy serum creatinine was 0.9 mg./dl. (normal 0.5 to 1.2). The operation was uncomplicated and the renal isograft has functioned well in C. W. without major problems. In 1977, 18 years after transplantation, C. W. underwent an open renal biopsy to evaluate microhematuria without proteinuria. Light microscopy of the transplanted kidney biopsy showed approx imately 40 glomeruli that were normal. The interstitium showed no infiltrates or fibrosis_ There were no vascular lesions. The microhematuria was believed to be secondary to a papilloma at Accepted for publication January 28, 1988. * Current address: Department of Nephrology, Presbyterian Medical Center, P. 0. Box 7999, San Francisco, California 94120. t Requests for reprints: Department of Medicine, Division of Nephrology and Hypertension, The Oregon Health Sciences University, 3181 S. W. Sam Jackson Park Rd., L463, Portland, Oregon 97201.
the left ureteral orifice, which was subsequently demonstrated on cystoscopy. C. C. was admitted to the Clinical Research Center at the Oregon Health Sciences University. She was a well developed, well nourished, 39-year-old woman who appeared to be in good health. She ate a normal diet without restriction of dietary protein or phosphate. Medical history was notable for allergies to penicillin and sulfa, 2 normal pregnancies and a total abdom inal hysterectomy in 1976. Physical examination revealed height 161 cm., weight 71.4 kg., body surface area 1.82 m. 2 and blood pressure 100/80. The rest of the examination was unremarkable except for the left nephrectomy and the midline hysterectomy scars. Laboratory examination showed blood urea nitrogen 16 mg./dl. (normal 10 to 20), creatinine 0.8 mg./dl., potassium 4.4 mg./dl. (normal 3.5 to 5.0), calcium 9.0 mg./dl. (normal 8.5 to 10.0), phosphate 2.7 mg./dl. (normal 2.3 to 4.0), albumin 4.0 gm.fl. (normal 3.6 to 5.0), white blood count 5,400/ mm. 3 (normal 5,000 to 10,000) and hematocrit 41.7 per cent (normal 38 to 43). Renal function data are shown in the table. A renal scan showed normal perfusion and glomerular and tubular function of the remaining right kidney. Ultrasound revealed a 12.2 X 6.1 cm. kidney. Inulin and paraaminohippuric acid clearances were 80 (normal 90 to 110) and 459 (normal 400 to 600) ml. per minute per 1.73 m.2, respectively. Acid loading with ammonium chloride (0.1 gm./kg.) caused a decrease in the urine pH for 6 hours from 7.33 to 5.09 (normal less than 5.2 for 6 hours) and a decrease in the serum bicarbonate from 29 to 20 mmol./1. (normal 25 to 29). DISCUSSION
Our 39 year-old renal donor remains in excellent health 27 years after unilateral nephrectomy. Blood pressure, serum electrolytes and 24-hour protein excretion are normal. Creatinine clearance is 75.9 per cent of the pre-nephrectomy determina-
Pt. age (yrs.) Blood pressure (mm. Hg) Creatinine (mg.fell.) Creatinine clearance (ml./min./1. 73 m.2) Inulin clearance (ml./min./1. 73 m.2) Paraaminohippuric acid clearance (ml./ min./1. 73 m. 2) Inulin/paraaminohippuric acid clearance ratio 24-hr. urine protein (mg.)
1959
1986
12 120/70 0.9 116
39 100/80 0.8 88 76.2 437.1 0.17
<150
<150
F{Et'~AL FUNCTIOI\J AFTER 1JNiLATERAL NEPI-IRECTOMY
vvhile inulin and cwJ,,u.Hvm~,;., acid clearances of 80 and 459 ml. per minute per m. 2 , respectively, with an inulin/ paraaminohippuric acid clearance ratio of 0.17, are similar to data reported in other more short-term acute studies. 6 - 8 In a study of 7 subjects 10 to 14 days after nephrectomy Pabico and associates found a mean inulin clearance of 75.8, mean paraaminohippuric acid clearance of 426.4 and an inulin/paraaminohippuric acid clearance ratio of 0.18. 6 In an assessment of renal function of 121 subjects who had donated a kidney 1 to 72 months previously Slack and Wilson found that mean residual inulin and paraaminohippuric acid clearances were approximately 70 per cent of pre-nephrectomy values, 7 while in 17 donors Ogden noted a mean inulin clearance of 85.9 and paraaminohippuric acid clearance of 317 ml. per minute per 1.73 ml. 2 22 to 48 months after nephrectomy. 8 The evaluation of our patient suggests that a young person can tolerate donor nephrectomy well and maintain an increase in solitary kidney glomerular filtration rate without sustaining any damage to remaining nephrons. This information is reassuring because of the findings in animal models of marked kidney mass reduction, suggesting that hyperfiltration of remaining nephrons can lead to glomerulosderosis and progressive renal insufficiency.' The normal biopsy of the transplanted kidney in the identical twin recipient 17 years after transplantation indicates that at that time there were no adverse effects of unilateral nephrectomy on renal pathology in the absence of rejection. The long-term outcome of living kidney donors is actively being studied at several transplant centers. Available data suggest that, despite a high incidence of mild proteinuria and a prevalence of hypertension no different from the population at large, no renal dysfunction develops in followup periods of 10 to 20 years. 2•5 In contrast, Miller and associates reported on 2 donors with the nephrotic syndrome and renal insufficiency, and an increased incidence of hypertension in 46 other donors with a mean followup of 6 years. 9 Thus, it will be important to determine whether donors of all ages are able to maintain an increase of approximately 40 to 50 per cent in glomerular filtration rate without the inevitable development of hypertension, proteinuria or damage to remaining nephrons.
811
that because donor neph:rectomy was done at a young age, it was better tolerated owing to a large renal reserve capacity. Thus, similar presentation of renal function might not be achieved if the donor were older. Although only a single case, the length of followup and the normal renal morphology in the twin recipient suggest that removal of a kidney can be safe for many years. uv,,en,cmo
REFERENCES 1. Brenner, B. M., Meyer, T. W. and Hostetter, T. H.: Dietary protein
2.
3.
4. 5.
6. 7. 8. 9.
intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. New Engl. J. Med., 307: 652, 1982. Talseth, T., Fauchald, P., Skrede, S., Dj0seland, 0., Berg, K. J., Stenstr0m, J., Heilo, A., Brodwall, E. K. and Flatmark, A.: Longterm blood pressure and renal function in kidney donors. Kidney Int., 29: 1072, 1986. Anderson, C. F., Velosa, J. A., Frohnert, P. P., Torres, V. E., Offord, K. P., Vogel, J. P., Donadio, J. V., Jr. and Wilson, D. M.: The risks of unilateral nephrectomy: status of kidney donors 10 to 20 years postoperatively. Mayo Clin. Proc., 60: 367, 1985. Smith, S., Laprad, P. and Grantham, J.: Long-term effect of uninephrectomy on serum creatinine concentration and arterial blood pressure. Amer. J. Kidney Dis., 6: 143, 1985. Williams, S. L., Oler, J. and Jorkasky, D. K.: Long-term renal function in kidney donors: a comparison of donors and their siblings. Ann. Intern. Med., 105: 1, 1986. Pabico, R. C., McKenna, B. A. and Freeman, R. B.: Renal function before and after unilateral nephrectomy in renal donors. Kidney Int., 8: 166, 1975. Slack, T. K and Wilson, D. M.: Normal renal function: CIN and CP AH in healthy donors before and after nephrectomy. Mayo Clin. Proc., 51: 296, 1976. Ogden, D. A.: Consequences of renal donation in man. Amer. J. Kidney Dis., 2: 501, 1983. Miller, I. J., Suthanthiran, M., Riggio, R. R, Williams, J. J., Riehle, R. A., Vaughan, E. D., Stubenbord, N. T., Mouradian, J., Cheigh, J. S. and Stenzel, K. H.: Impact of renal donation. Long-term clinical and biomedical follow-up of living donors in a single center. Amer. J. Med., 79: 201, 1985.
THE JOURNAL OF UROLOGY
Copyright © 1988 by The Williams & Wilkins Co.
RENAL FUNCTION 27 YEARS AFTER UNILATERAL NEPHRECTOMY FOR RELATED DONOR KIDNEY TRANSPLANTATION LAWRENCE L. BOHANNON,* JOHN M. BARRY, DOUGLAS J. NORMAN AND WILLIAM M. BENNETTt From the Renal Transplant Service, Divisions of Nephrology and Urology, The Oregon Health Sciences University, Portland, Oregon
ABSTRACT
Renal function in a living related kidney donor was evaluated 27 years after unilateral nephrectomy. The patient was normotensive and had no significant proteinuria. Creatinine was 0.8 mg. per dl. and creatinine clearance was 88 ml. per minute per 1. 73 m. 2 or 152 per cent of the single kidney pre-nephrectomy value. Tubular function assessed by the ability to lower urinary pH in response to an acid load was normal. Biopsy of the transplanted kidney 18 years after donation was histologically normal. This case represents one of the longest followup evaluations of a living related donor reported to date and it argues against any adverse effects of organ donation on the function of the remaining kidney. (J. Ural., 140: 810-811, 1988) The productive lives of many individuals with end stage renal disease have been extended because a living relative donated a kidney for transplantation. Recipients of living related donor kidneys fare significantly better than their cadaveric recipient counterparts in terms of patient and graft survival, and incidence of complications. Concerns about the long-term consequences of renal donation have recently arisen because of experimental evidence documenting glomerular hyperfiltration with increased intraglomerular pressures as a result of ablation of a renal mass. 1 Indeed, urinary albumin excretion is increased compared to age-matched controls in kidney donors studied 9 to 15 years after donation. 2 Development of renal dysfunction has not been observed and although hypertension develops in some patients its prevalence is not greater than the general population. 3- 5 However, since living related donors tend to be in the third and fourth decades of life, followup periods even as long as 10 to 20 years may be insufficient to observe clinical evidence of decreased renal function. We report a detailed evaluation of a woman who donated a kidney for transplantation 27 years ago. She was the first living, related kidney donor at the Oregon Health Sciences University in October 1959. CASE REPORT
C. C., a 39-year-old white woman, had undergone left donor nephrectomy on October 9, 1959 when she was 12 years old to provide an isograft for her identical twin sister C. W. C. W. had end stage disease secondary to chronic glomerulonephritis. Before nephrectomy C. C. underwent a complete medical evaluation, including an excretory urogram (normal) and a 12-hour creatinine clearance (116 ml. per minute per 1.73 m. 2 ). Prenephrectomy serum creatinine was 0.9 mg./dl. (normal 0.5 to 1.2). The operation was uncomplicated and the renal isograft has functioned well in C. W. without major problems. In 1977, 18 years after transplantation, C. W. underwent an open renal biopsy to evaluate microhematuria without proteinuria. Light microscopy of the transplanted kidney biopsy showed approx imately 40 glomeruli that were normal. The interstitium showed no infiltrates or fibrosis_ There were no vascular lesions. The microhematuria was believed to be secondary to a papilloma at Accepted for publication January 28, 1988. * Current address: Department of Nephrology, Presbyterian Medical Center, P. 0. Box 7999, San Francisco, California 94120. t Requests for reprints: Department of Medicine, Division of Nephrology and Hypertension, The Oregon Health Sciences University, 3181 S. W. Sam Jackson Park Rd., L463, Portland, Oregon 97201.
the left ureteral orifice, which was subsequently demonstrated on cystoscopy. C. C. was admitted to the Clinical Research Center at the Oregon Health Sciences University. She was a well developed, well nourished, 39-year-old woman who appeared to be in good health. She ate a normal diet without restriction of dietary protein or phosphate. Medical history was notable for allergies to penicillin and sulfa, 2 normal pregnancies and a total abdom inal hysterectomy in 1976. Physical examination revealed height 161 cm., weight 71.4 kg., body surface area 1.82 m. 2 and blood pressure 100/80. The rest of the examination was unremarkable except for the left nephrectomy and the midline hysterectomy scars. Laboratory examination showed blood urea nitrogen 16 mg./dl. (normal 10 to 20), creatinine 0.8 mg./dl., potassium 4.4 mg./dl. (normal 3.5 to 5.0), calcium 9.0 mg./dl. (normal 8.5 to 10.0), phosphate 2.7 mg./dl. (normal 2.3 to 4.0), albumin 4.0 gm.fl. (normal 3.6 to 5.0), white blood count 5,400/ mm. 3 (normal 5,000 to 10,000) and hematocrit 41.7 per cent (normal 38 to 43). Renal function data are shown in the table. A renal scan showed normal perfusion and glomerular and tubular function of the remaining right kidney. Ultrasound revealed a 12.2 X 6.1 cm. kidney. Inulin and paraaminohippuric acid clearances were 80 (normal 90 to 110) and 459 (normal 400 to 600) ml. per minute per 1.73 m.2, respectively. Acid loading with ammonium chloride (0.1 gm./kg.) caused a decrease in the urine pH for 6 hours from 7.33 to 5.09 (normal less than 5.2 for 6 hours) and a decrease in the serum bicarbonate from 29 to 20 mmol./1. (normal 25 to 29). DISCUSSION
Our 39 year-old renal donor remains in excellent health 27 years after unilateral nephrectomy. Blood pressure, serum electrolytes and 24-hour protein excretion are normal. Creatinine clearance is 75.9 per cent of the pre-nephrectomy determina-
Pt. age (yrs.) Blood pressure (mm. Hg) Creatinine (mg.fell.) Creatinine clearance (ml./min./1. 73 m.2) Inulin clearance (ml./min./1. 73 m.2) Paraaminohippuric acid clearance (ml./ min./1. 73 m. 2) Inulin/paraaminohippuric acid clearance ratio 24-hr. urine protein (mg.)
1959
1986
12 120/70 0.9 116
39 100/80 0.8 88 76.2 437.1 0.17
<150
<150
F{Et'~AL FUNCTIOI\J AFTER 1JNiLATERAL NEPI-IRECTOMY
vvhile inulin and cwJ,,u.Hvm~,;., acid clearances of 80 and 459 ml. per minute per m. 2 , respectively, with an inulin/ paraaminohippuric acid clearance ratio of 0.17, are similar to data reported in other more short-term acute studies. 6 - 8 In a study of 7 subjects 10 to 14 days after nephrectomy Pabico and associates found a mean inulin clearance of 75.8, mean paraaminohippuric acid clearance of 426.4 and an inulin/paraaminohippuric acid clearance ratio of 0.18. 6 In an assessment of renal function of 121 subjects who had donated a kidney 1 to 72 months previously Slack and Wilson found that mean residual inulin and paraaminohippuric acid clearances were approximately 70 per cent of pre-nephrectomy values, 7 while in 17 donors Ogden noted a mean inulin clearance of 85.9 and paraaminohippuric acid clearance of 317 ml. per minute per 1.73 ml. 2 22 to 48 months after nephrectomy. 8 The evaluation of our patient suggests that a young person can tolerate donor nephrectomy well and maintain an increase in solitary kidney glomerular filtration rate without sustaining any damage to remaining nephrons. This information is reassuring because of the findings in animal models of marked kidney mass reduction, suggesting that hyperfiltration of remaining nephrons can lead to glomerulosderosis and progressive renal insufficiency.' The normal biopsy of the transplanted kidney in the identical twin recipient 17 years after transplantation indicates that at that time there were no adverse effects of unilateral nephrectomy on renal pathology in the absence of rejection. The long-term outcome of living kidney donors is actively being studied at several transplant centers. Available data suggest that, despite a high incidence of mild proteinuria and a prevalence of hypertension no different from the population at large, no renal dysfunction develops in followup periods of 10 to 20 years. 2•5 In contrast, Miller and associates reported on 2 donors with the nephrotic syndrome and renal insufficiency, and an increased incidence of hypertension in 46 other donors with a mean followup of 6 years. 9 Thus, it will be important to determine whether donors of all ages are able to maintain an increase of approximately 40 to 50 per cent in glomerular filtration rate without the inevitable development of hypertension, proteinuria or damage to remaining nephrons.
811
that because donor neph:rectomy was done at a young age, it was better tolerated owing to a large renal reserve capacity. Thus, similar presentation of renal function might not be achieved if the donor were older. Although only a single case, the length of followup and the normal renal morphology in the twin recipient suggest that removal of a kidney can be safe for many years. uv,,en,cmo
REFERENCES 1. Brenner, B. M., Meyer, T. W. and Hostetter, T. H.: Dietary protein
2.
3.
4. 5.
6. 7. 8. 9.
intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. New Engl. J. Med., 307: 652, 1982. Talseth, T., Fauchald, P., Skrede, S., Dj0seland, 0., Berg, K. J., Stenstr0m, J., Heilo, A., Brodwall, E. K. and Flatmark, A.: Longterm blood pressure and renal function in kidney donors. Kidney Int., 29: 1072, 1986. Anderson, C. F., Velosa, J. A., Frohnert, P. P., Torres, V. E., Offord, K. P., Vogel, J. P., Donadio, J. V., Jr. and Wilson, D. M.: The risks of unilateral nephrectomy: status of kidney donors 10 to 20 years postoperatively. Mayo Clin. Proc., 60: 367, 1985. Smith, S., Laprad, P. and Grantham, J.: Long-term effect of uninephrectomy on serum creatinine concentration and arterial blood pressure. Amer. J. Kidney Dis., 6: 143, 1985. Williams, S. L., Oler, J. and Jorkasky, D. K.: Long-term renal function in kidney donors: a comparison of donors and their siblings. Ann. Intern. Med., 105: 1, 1986. Pabico, R. C., McKenna, B. A. and Freeman, R. B.: Renal function before and after unilateral nephrectomy in renal donors. Kidney Int., 8: 166, 1975. Slack, T. K and Wilson, D. M.: Normal renal function: CIN and CP AH in healthy donors before and after nephrectomy. Mayo Clin. Proc., 51: 296, 1976. Ogden, D. A.: Consequences of renal donation in man. Amer. J. Kidney Dis., 2: 501, 1983. Miller, I. J., Suthanthiran, M., Riggio, R. R, Williams, J. J., Riehle, R. A., Vaughan, E. D., Stubenbord, N. T., Mouradian, J., Cheigh, J. S. and Stenzel, K. H.: Impact of renal donation. Long-term clinical and biomedical follow-up of living donors in a single center. Amer. J. Med., 79: 201, 1985.