November 1991 REFERENCES 1. Anuras 8, Piros J, Bonney W, Forker EL, Colville DS, Corry RJ. Liver disease in renal tranaplant recipients. Arch Intern Med 197%; 197: 42. 2, Debure A, Degos F, Pol S, etal. Liver diseases and hepatic com: plications in renal transplent patients. Adv Nephrol 1988; 17: 315, 3. Parfrey PS, Forbes RDC, Hutchinson TA, et al. The impact of ‘enal transplantation on the couree of hepatitis B liver disease. ‘Transplantation 1985; 39: 610. 4, Weissberg JI, Andres LL, Smith Cl, et al. Survival in chronic hepatitis B: an analysis of 379 patients, Ann Intern Med 1984; 101: 613, 5, Ware AJ, Luby JP, Hollinger B, etal. Etiology of liver disease in renal transplant patients, Ann Intern Med 1973; 6, Boyce NW, Holdsworth SR, Hooke D, Thomson NM, Athi 'Non-hepattis B associated liver divease in a rensl transplant population. Am J Kidney Dis 1988; 4: 07, 1. Kuo G, Choo QL, Alter Hi etal. An assy for circulating antibodies to a major etiologic virus of human non-A non-B hepatitis. Science 1989; 244 362, 041-1337/9/6206-0813808.00/0, ‘TransPtantaron Copyright © 1881 by Wiliams & Wilkine HAYES ET AL. 813 8, Yeoh EK, Chang WK, Kwan JPW. Epidemiology of viral hepatitis B infection in Hong Kong. In: Lam SK, ed. Viral hepatitis B infection in the western Pacific region’ vaccine and contro Singapore: World Scientifie, 1984: 38. 9, Pons F, CempistolJ, Barrera J, et al. Incidence and role of hepatitis (C virus (HCV) in liver disease of renel transplant patients [Abstract]. Abstesct no. 434, 13th International Congress of the ‘Transplantation Society, Sen Francisco, August, 1990. 10, Pot 8, Legendre C, Saltiel C, et al. Hepatitis C virus in kidney ‘recipients: epidemiology; impact on renal transplantation (Ab: Abstract. no. 403, International Symposium on Viral Hepatitis and Liver Disease, Houston, 1990, 1, Alter HJ, Purcell RH, Shik JW, et al. Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A non-B hepatitis, N Engl J Med 12, Huang CC, Lai MK, Fong MT. Hepatitis B liver disease in cyclo- sporine-treated renal allograft recipients. Transplantation 1990; 49: 540, Received 20 December 1990, Accepted 22 March 1991 Vol 52, 819-817, No. 5, November 1991, Prntedin CSA THE DEVELOPMENT OF PROTEINURIA AND FOCAL- SEGMENTAL GLOMERULOSCLEROSIS IN RECIPIENTS OF PEDIATRIC DONOR KIDNEYS Josep M. Hayes, * Donatp R. STEINMULLER,’ STEVAN B. STREEM’ AND ANDREW C. Novick! Departments of Urology and Hypertensian/ Nephrology, The Organ Transplantation Center, The Cleveland Clinie Foundation, Several reports in animals, and sporadic case reports in humans, have suggested that kidneys with decreased nephron mass may be more susceptible to the develop- ment of focal-segmental glomerosclerosis. ‘Thi prompted a reexamination of our previously reported group of pediatric donor-adult recipient renal tran: plant combinations. Data were analyzed from 31 adult recipients who had received renal transplants from ca- daver pediatric donors (<6 years) with graft function for >6 months and no evidence of chronic rejection. ‘These were compared with a control group transplanted during the same period with adult donor kidneys. Im- munosuppression consisted of azathioprine/prednisone or quadruple therapy in 16 and 15 patients respectively. End-stage renal disease (ESRD) was secondary to chronic glomerulonephritis (n=9), diabetes mellitus (n=6), polycystic kidney disease (n=5), and miscell neous causes (n=11). Twenty patients had radiographic documentation of renal hypertrophy posttransplant. All * Department of Urology * Address correspondence to: Joseph M. Hayes, M.D., The Cleveland (Clinic Foundation, 9500 Euclid Ave, Desk A100, Cleveland, OH 44195. Department of Hypertension/Nephrolog. (Cleveland, Ohi 44106 patients had serial 24-hr urinalysis for protein and cre- atinine after transplantation during periods of stable renal function, Ten patients had renal biopsies per- formed at a mean time from transplant to biopsy of 10.441.6 months. Seven recipients had biopsies that revealed glomerulosclerosis at 1346 months posttrans- plant. Protein excretion and serum creatinine in these Patients were significantly higher than in control pa tients (1.6£0.37 vs. 0.49+0.15 g/24 hr and 1.96+0.11 ‘ya. 1,640.08 mg%: P<0.03 and P<0.01, respectively). Only 3 of 25 control adult donor recipients developed proteinuria > 0.8 g/24 hr within 2 years of transplan- tation vs. 16/31 pediatric donor recipients. No correl tions with the etiology of ESRD, age (>or< 40 years), weight, sex, diabetes, hypertension, or the number of acute rejection episodes could be found. Our data suggest that adult recipients of pediatric donor renal transplants may be at greater risk for the development of glomeru- losclerosis than those recipients receiving adult donor kidney: ‘The rapidly widening gap between the number of patients ‘awaiting solid organ transplants and the availability of donor ‘organs has prompted many transplant centers to reevaluate814 and expand their criteria for donor acceptability. The use of pediatric cadaver donor kidneys has remained controversial and discrepant results continue to be reported'(1-5). We have previously reported our experience over the past decade utiliz: ing these kidneys (6), and have found sequential immunosup- pressive therapy to improve results when utilizing kidneys from donors under 6 years of age. The enhanced protection from ‘both ischemic insult and rejection may be of critical importance in this situation with perhaps less than adequate functional renal reserve. Concerns regarding an inadequate nephron mas when these small kidneys are transplanted into adults have ‘been cited by some authors who advocate en bloc transplanta- tion of both kidneys (8-10), ‘Several reports have highlighted a potential long-term path- logic change in the kidney with an inadequate nephron m that is, the development of progressive glomerulosclerosis, (GS).* Studies in animals (11-13) and sporadic reports in hhuman (14-17) have suggested an enhanced susceptibility to the development of GS both in kidneys from younger individ. ‘uals and in individuals with decreased nephron mass, These studies have prompted us to reexamine our transplant recipi ‘ents who received pediatric cadaver kidneys from donors under 6 years of age. MATERIALS AND METHODS Patients. Between May 1977 and June 1987 57 uremic adult patients received renal transplants utilizing kidneys procured from pediatric ‘eadaver donors aged 0 to 6 years. A group of 25 adult donor (> 16 years ‘of age) renal transplant recipients matched for immunosupprestion, ‘time period of transplantation, recipient ag, histocompatibility, total and warm ichemia time, incidence of rejection, and diabetic and retransplant status, served as controls. Protocols for perioperative and postoperative care. All kidneys were harvesteden block from heart-beeting cadaver donors and transplanted 1a single units. Ureteroneoeystostomy was performed in all cases Simple cold storage with Collin solution was used for preservation Immunosuppression consisted of either conventional therapy with ‘azathioprine, prednisone, and prophylactic antilymphocyte globulin or sequential therapy utilizing low-dose azathioprine, prednisone, tnd prophylactic ALG, with conversion to cyclosporine aa previously de scribed (6). Rejection episodes were treated with intravenous methyl prednisolone 1.5 g in divided doses and/or ALG (10-20 mg/kg) of OKTS (5 mg) for 10 days. Renal function was assessed by serum creatinine, creatinine clearance, and/or glomerular filtration rates by ts modification of the method of Iaraelit et al. (18). Renal biopsies ‘obtained after the initial 6-month posttransplant period were per formed in patients with relatively rapid deterioration in renal function to rule out rejection, or in patients with increasing proteinuria with oF without stable renal function, Eligibility criteria, All pediatric cadaver donors had function and no history of proteinuria or underlying renal to the many preexisting factors in this study population that might influence the interpretation of data leading to a diagnosis of GS posttransplantaton, strict criteria were established for patient entry into both study and control groups. Patients in whom the etiology of ‘end-stage renal disease (ESRD) could result in the development of {ocal and/or segmental GS, such aa Fabry's disease, Alpor's syndrome, oF preexisting GS, were excluded from analysis, Those patients in whom chronic rejection was suspected by biopsy and a history of sraduilly deteriorating renal function, estociated temporally with in ‘reasing proteinuria and the development or worsening of hypertension, were excluded. In most cases these clinical erteria were accompanied * Abbreviations: ACE, angiotensin-converting enzyme; ESRD, end: stage renal disease; GS, glomerulosclerosis, "TRANSPLANTATION Vol. 52, No.5 by pathologie changes such as vasculitis, ibrin-platelet deposits, sub- endothelial membranous material deposits, and the absence of foot process loss and capillary loop collapse on electron microscopy. Those ‘whose biopsies were performed to confirm clinically suspected acute rejection were exclude. Patients entered into the analysis had to have no evidence of acute ‘or chronic rejection by the above erteria. Adequate laboratory data defined as seriel measurements of serum creatinine, creatinine clear. tance, and 24-hr urinary protein excretion were required. In order to enture the adequacy ofthe 24-hr urine collection, the specimen had to contain between 10 and 25 mg of eretinine per kg body weight. Pathologic criteria used forthe diagnosis of GS included the follow- ing: focal or segmental GS and/or hyalinosis with minimal or no pathologic changes in the nonsclerotic glomeruli; tubular lose end interstitial fibrosis; and immunofluorescence studies revealing focl and segmental granular deposits of IgM and C in the mesangial regions of glomeruli. Electron microscopic criteria included foot process fusion and lose, wrinkled and thickened glomerular capillary basement mem: branes in the areas of sclerosis, and capillary lop collapse. ‘Statistical methods. Compariton between demographic and disease history variables, as well as rejection incidence, were analyzed by Student's ¢ test. Appropriate two-way tables for categorical variables were developed, with ci-squere analyses ured to test for independence (19). When sample size was small, andthe expected cll frequency wa leas than five, the Fisher's exact test was used for analysis (20). RESULTS Patient entry and clinical characteristics, Established eligibil- ity criteria were met by 31 of 57 adult recipients of renal transplanta utilizing kidneys from pediatric donors age 0-6 years, Summary data on demographic factors, immunosuppres- ion, and pertinent medical history, including the etiology of ESRD and the incidence of retransplantation, are shown in Table 1. The period of follow-up from transplantation was comparable for the study and control patients. There were no statistically significant differences noted for recipient age, di- abetic or retransplant status, or the type of immunotuppres- ion. In addition, ischemia time and the degree of histocompat- ibility were similar. No statistically significant correlations existed between any of the variables in Table 1 and subsequent proteinuria and/or GS. ‘Rejection and hypertension. Patients in whom historical and/ or pathologic evidence confirmed or suggested a diagnosis of chronic rejection were eliminated from consideration. Twenty- ‘two and 13 recipients in the study and control groups respec- tively had one or more acute rejection episodes. This difference ‘was not statistically significant, In the study group 1, 8, and 13 recipients experienced 3, 2, and 1 acute rejection episodes respectively. In 19 of these 22 patients renal function returned episodes respectively. In 19 of these 22 patients renal function returned to baseline after antirejection therapy. Three of the 8 recipients with two rejection episodes lost their grafte as a result of the second rejection episode. In no recipient was the development of proteinuria or a diagnosis of GS temporally related to an acute rejection episode. It is of note that 5 recipients subsequently found to have proteinuria did not have clinically evident rejection episode. While no significant correlations were noted between acute rejection episodes and the subsequent development of GS or proteinuria, « trend toward an association between rejection and proteinuria may be present (P=0.06). Hypertension was present in 14 study group recipients post- ‘transplant. In 3 of these patients the hypertension was stable ‘comparison to pretransplant, and in 11 patients hypertension[Noversber 1991 ‘Tanue 1. Demographic and clinical characteristics of patients receiving pediatric (study) and adult (control) donor renal transplants ody BT) Sex (M/F) 20/11 Recipient age (years)* 374223 Donor age (years)* 33203 ‘Time of follow-up 295236 months)" No. with prior transplants 2 No. with eyclosporine im 15 u ‘munosuppression Btiology of ESRD Diabetes mellitus 6 u Polyeyatic kidney dis 5 (Chronic glomeruloneph- ° tits Miscellaneous (eg, con- n 6 either developed or worsened posttransplant. Two of these 11 patients were subsequently found to have renal artery stenosis that responded to percutaneous transluminal angioplasty. Hy pertension was treated with angiotensin-converting enzyme (ACE) inhibitors, in conjunction with other antihypertensives, in 4 patients, and with beta blockers in an additional 3 patients. ‘Twenty-two control group recipients had hypertension post ‘transplant. In 9 of these patients hypertension either developed ‘or worsened posttransplant. ACE inhibitors were utilized as antihypertensive therapy in 10 of the 22 recipients. ‘No correlations existed between the incidence, severity, or development of hypertension, or antihypertensive therapy with or without ACE inhibitors, and the subsequent development of proteinuria and/or GS. However, a possible trend between hypertension and the subsequent development of proteinuria and GS was evident (P=0.08 and P=0.07 respectively). Four recipients who developed GS had hypertension, and three of these patients were being treated with ACE inhibitors, while the remaining patient received a beta blocker. In 2 of 4 recipi- ents with hypertension and GS, the hypertension was stable relative to the pretransplant period. Renal function, proteinuria, and glomerulaselerosis. All recip ients of pediatric kidneys who were studied early after trans plantation with ultrasound or CT imaging subsequently under. ‘went a later, repeat study to determine if renal hypertrophy hhad occurred. In all patients studied (n=20) significant hyper trophy had occurred, with the kidney doubling, or even tripling, in estimated volume. In examining the entire group of selected study patients, a significant difference was noted in serum creatinine compared with that of control patients, While the creatinine clearance and GFR performed in a smaller cohort were not statistically different from those of controls, a trend toward decreased renal function in the study group is suggested by the data summarized in Table 2. The serum creatinine for recipients with GS on biopsy (n=7) and for all recipients with proteinuria (n=15) was similar to that in the entire study group (1,910.12, 1,970.17, and 1.96:0.11 respectively). “Measurements of urinary protein in both study and control patients was analyzed only during periods of stable renal fune- tion, that is, in the absence of rejection and of medical or surgical complications. Data regarding proteinuria in study and HAYES ET AL. 815 control patients are summarized in Table 3. Urinary protein fexeretion per 24 hr was significantly greater in the study vs, control group recipients, Protein excretion greater than 08 g/ 24 hr was noted in 15 of 31 study recipients vs. 3 of 25 control recipients (P<0.01). One control patient with poorly controlled diabetes, and hypertension treated without ACE. inhibitor excreted 4g of protein/24 hr and had a stable serum creatinine Of L8 mg after 8 years of follow-up. Proteinuria in this patient may have been secondary to recurrent diabetes and exacerbated by hypertension. All patients with proteinuria, with proteinuria and no biopsy, and with evidence of GS on biopsy, had signif. ‘cantly inereased urinary protein excretion compared with con trol patients Seven recipients were found to have evidence of GS on renal biopsy performed at a mean time posttransplant of 10.481.6 months. In 3 ofthese recipients renal biopay was performed to assess an increase in serum creatinine of 0.5 mgt over a 2 ‘month period The mean serum creatinine in these 3 recipients twas 1.7 mg% (range 1.4-2.0 mg%). The remaining 4 recipients had stable renal function at the time of biopsy, with a mean serum crentinine of 2.1 mg% (range 1.8-2.3 mp’), and under- went biopsy ostensibly to assess incressing proteinuria Four af the 7 patients hed studies posttransplant documenting sig nificant hypertrophy of the renal transplant ‘The etiology of ESD in these 7 patients was congenital anomaly or anatomic abnormality (e.g., vesicoureteral reflux with chronic pyelonephritis) in 4 patienis, and polycystic kid- ney disease, chronic glomerulonephritis, and diabetes mellitus in one patient each. ‘The patient with diabetes was well con- trolled, had his renal biopsy performed at 13 months posttrans- plantation, and had no evidence ofthe nodular type of GS on biopsy Five of these 7 patients with GS had one rejection episode, which was mild and reversed without impairment in renal funetion. The remaining 2 patients had two rejection episode TABLE 2 Assessment of renal function in study and control ecipients Study (aS) Control (26) P vue Renal hypertrophy 20/81 Serum creatinine 1962011 164x009 0.08 (amg’ey" Creatinine clearance 425845 © L785.2 NSP (ini/min) GFR (ml/min) 419245 578104 NS t 1) Mean = SEM. NS: not significant Tams Proteinuria im study and control patients Urinary pro: tein (pes Urinary pro Urinary pr teintallpa tentawth tein pe ‘ein tll pa 7 infall PO. ent with proteinuria tents with ents) proteinuria) ander GS Study (6/24 337K062 0080.77 2612109 (n=i5) (nell) 1952091 (n=3) 0.05,816 ‘While renal function returned to baseline after the first rejec- tion episodes, these 2 recipients subsequently lost their allo- ‘rafts to second acute rejection episodes occurring greater than 1 year posttransplant, DISCUSSION, ‘The concept that @ decrease in the number of functioning nephrons, beyond an unknown critical limit, may lead to glo- merular hyperfltration was introduced over 50 years ago (2!) ‘That this physiological adaptation may induce a functional overload on the remaining renal units, with resultant detrimen- tal glomerular changes, has been suggested from animal studies (11, 22, 23). Hostetter et al., based on substantial experimental evidence, have proposed that this compensatory hyperfiltration ‘may be maladaptive and result in progressive renal injury (22, 23). The work of Olson et al. further supported this hypothesis by demonstrating in rate that a significant reduction in renal ‘mass resulted in the remnant glomeruli developing various functional defects such as capillary membrane disruption with resultant loss of size and charge-selectivity (24). Proteinuria ‘appears to be the hallmark of this glomerulopathic process. It ‘appears that after a critical reduction in renal mass, progressive destruction of remnant glomeruli occurs, possibly involving several common pathways, one of which is hyperfiltration of residual renal units, In addition, protein may independently influence renal hemodynamics and play a significent role in pathogenesis, Studies in both animals and humans have dem- ‘onstrated an increase in renal mass, GFR, and renal blood flow after protein feeding (25-28). Kiprov et al. reported the devel ‘opment of proteinuria and subsequent focal/segmental glomer- ulosclerosis in surgical pathology and autopsy specimens from patients with solitary kidneys (14). Thorner et al. described similar pathologic findings in three children with solitary kid- neys and chronic renal failure (15). Various case reports have 0 illustrated these abnormalities after surgical removal of 178% of functioning renal mass (29, 30). Identifying the abnormal development of proteinuria and/or GS in the setting of renal transplantat problems. Proteinuria is frequently associated with various pathologic development post-renal transplantation. GS may be the primary etiology of ESRD, or secondary to a number of diseases leading to ESRD such as Alport’s eyndrome, Fabry’s disease, or primary focal-segmental GS. In addition, other clinical and pathologic findings in chronic rejection and/or cyclosporine nephrotoxicity may be similar, although not iden- tical, to those noted with the development of focal-segmental bility criteria were established in an attempt to interpretation of proteinuria or identification of GS ient population, ‘While the transplantation of pediatric donor kidneys into adult recipients results in a decreased renal mass relative to patient size, and may enhance the development of proteinuria, or GS, pedistric donor kidneys may be inherently more suscep- tible to these pathologic developments. Okuda et al. found significantly increased compensatory hypertrophy, proteinuria, ‘and focal glomerulosclerosis in younger rats undergoing uni: ‘nephrectomy (13). While there have been reports with long- term follow-up of the successful utilization of neonatal anen- cephalic donors (31), Leunissen et al. reported two adult recip- iente of en-bloc neonatal kidneys who developed proteinu tand subsequent focal glomerulosclerosis (16). Woolley et al "TRANSPLANTATION Vol. 52, No.8 also reported a case of nephrotic range proteinuria and de novo focal glomerulosclerosis in an adult recipient of a single kidney from a 6-year-old donor (17). Whether pediatric kidneys are inherently more susceptible to this pathologic development remains unknown. The significant differences in protein excre- tion noted between our study and control patients, without differences in factors that might contribute to the development of proteinuria, further support the preceding hypotheses. ‘A decrease in the relative amount of functioning renal paren- cchyma due to acute rejection episodes may result in posttrans- plant proteinuria. In our study patients we were not able to identify a correlation between acute rejection and proteinuria ‘or GS. In all acute rejection episodes occurring prior to the identification of proteinuria there was complete reversal with antirejection therapy, and a return to the level of previous renal ion. In eddition, most of these rejection o early after transplantation in a relatively small patient popu- lation. Functioning renal mass relative to the patient's size is difficult to as ‘on biopsy had marked compensatory hypertrophy noted, with at least a doubling in renal volume. Furthermore, no correlation was noted between recipient weight or donor age and the development of proteinuria or GS. Diabetes, which may result in nephropathy and the development of proteinuria and GS, was present in only 1 of 7 recipients with GS and in 3 of the 15 patients with proteinuria, Renal function, as assessed by the serum creatinine, was ignificantly different for all study versus control patients. However, other parameters of renal function, while suggestive of a trend, were not significantly different from those of control patients. It should be noted, however, that follow-up is rela tively short (3 years), and a longer time period may be required to demonstrate deterioration of renal function. In summary, the impact of our findings, as they relate to the utilization of pediatric donors for renal'transplantation, re- mains uncertain. Certainly available experimental and clinical ‘evidence would suggest that adult recipients of smaller pediatric donor kidneys may be at significant risk to develop glomerular hyperfitration and proteinuria, However, the large number of confounding variables present in the transplant setting make GS a difficult entity to study. Further long-term studies should ideally be done in a controlled, prospective manner with serial biopsies to evaluate the extent and significance of this potent complication following the transplantation of smaller pediatric donor kidneys into adult recipients. REFERENCES 1. Opelz G. Influence of recipient and donor age in pediatric renal transplantation. Transplant Int 1988; 1:95. 2, Wengerter K, Matas AJ, Telli VA, Quinn T, Soberman , Veith J. Transplantation of pediatric donor kidneys to adult recipi- ‘ents: is there a ertial donor age? Ann Surg 1986; 204: 172, 3. Ruder H, Schaefer F, Gretz N, Mohring 8, Scharer K. Donor Kidneys of infants and very young children are unacceptable for ‘transplantation. Lancet 1988; 2: 168, 4, Fine RN. Renal traneplantation of the infant and young child and ‘the use of pediatric eadaver donor kidneys for traneplantation in pediatric and adult recipients. Am J Kidney Dis 1988; 12:1. 8, Smith AY, Van Buren CT, Lewis RM, Kerman RH, Kahn BD. Short-term and long-term function of cadaveric kidneys from pediatric donors in recipients treated with cyclosporine. Trans- plantation 1988; 45: 360. 6, Hayes JM, Novick AC, Streem SB, eta The use of singe pediatricNovember 1991 cadaver kidneys for transplantation, Transplantation 1988; 45: 106. 17. Hayes JM, Novick AC, Steinmuller DR, et al. Improved results ‘using pediatric cadaver donor kidneys with cyclosporine immu- nosuppression. Transplant Proc 1988; 20: 200. 8, Meakins JL, Smith BJ, Alexander JW. En bloc transplantation of both kidneys from pediatric donors into adult patents. Surgery 1993; 71: 72 9, Anderson OS, Jonasson O, Merkel FK, En bloc transplantation of pediatric kidneys into adult patients. Arch Surg 1974; 108 35. 10, Schneider JR, Sutherland DER, Simmons RL, Fryd DS, Nejarian ‘38. Long-term success with double pediatric cadaver donor renal ‘transplants. Ann Surg 1983; 197: 439, 11, Shimamura T, Morrison AB. A progrestive glomeruloscleross oc. curring in partial five-sixths nephrectomized rats. Am J Pathol 1975; 78: 95. 12, Brenner BM, Meyer TW, Hostetter TH. Dietary protein intake tnd the progressive nature of kidney disease: the role of hemo- lly mediated glomerular injury in the pathogenesis of, ive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. N Engl J Med 1982; 307: 652 18, Okuda §, Motomura K, Sanai , otal. Influence of age on deteri oration of the remnant kidney in uninephrectomized rats, Clin Sci 1981; 72: 571 14, Kiproy DD, Colvin RB, McCluskey RT. Focal and segmental lomerulosclerosis and proteinuria associated with unilateral renal agenesis. Lab Invest 1982; 6: 276 15, Thorner PS, Arbus GS, Celermajer DS, Baumal R.Focel segmental slomerulosclerosis and progressive renal failure associated with ‘unilateral kidney. Pediatrics 1984; 73: 806, 16, Leunissen KM, Kootstra G, Bosman PT, van Hooff JP. Focal slomerulosclerosi in neonatal kidney graft. Lancet 1987; 2 1019. 17, Woolley AC, Rosenberg ME, Burke BA, Nath KA. De novo focal slomeruloscleross after kidney transplantation, Am J Med 1988; 84: 310, 18. Iraclit AH, Lanz DC, White MG, Hall AZ. Measurement of GFR utilizing @ single subcutaneous injection of [-labelled sodium fothalemete (Gloft). Kidney Int 1973, 4:94. HAYES ET AL. 817 19, Mantel N, Haenszel W. Statistical aspects ofthe anelyses of data from retrospective studies of disease. INCI 1959; 2: 718. 20, Fisher RA. Statistical methods for research workers. 14th. New York: Hafner, 1973; 96. 21, Chanutin A, Ferris E. Experimental renal inauficiency produced by partial nephrectomy. Arch Intern Med 1932; 48: 767 22, Hostetter TH, Olson JL, Rennke HG, Venkatachalam MA, Bren- ner BM, Hyperfitration in remnant nephrons: a potentially ‘adverse response to renal ablation. Am J Physiol 1981; 241: FBS, 28, Hostetter TH, Rennke HG, Brenner BM. Compensstory renal ‘hemodynamic injury: a final common pathway of residual neph- zon destruction. Am J Kidney Dis 1982; 1: 310. 24, Olson JL, Hostetter TH, Rennke HG, Brenner BM, Venkatach- ‘alam MA. Altered glomerular permsclectivity and progressive sclerosis following extreme ablation of renel mass. Kidney Int 1982; 22: 112. 25. MacKay BM, MacKay LL, Addis’T, Factors which determine renal weight: V. The protein intake. Am J Physiol 1928; 66: 459 26, O'Connor WJ, Summerill RA. The effect of a meal of meat on ‘lomeruar filtration rte in dogs at normal urine lows. J Physiol 1976, 256: 8. 27, Pullman TN, Alving AS, Dern RJ, Landowne M. The influence of dietary protein intake on specific renal functions in normal man ‘JLab Clin Med 1984; 44: 320 28. Cochran ST, Pagani JJ, Barbaric ZL. ‘mentation, Radiology 1979; 190: 608. 29, Solomon LR, Mallick NP, Lawler W. Progrestive renal fs ‘remnant kidney. Br Med J 1985; 291: 1610. 80, Stahl RAK, Low I, Schoeppe W. Progressive renal failure in a patient after one and two-thirds nephrectomy. Klin Wochenschr 1988; 6: 508. 41, litaka K, Martin LW, Cox JA, McEney PT, West CD. Transplan- tation of cadaver kidneys from anencephalic donors, J Pediatr 1978; 93 26. pphromegaly in hyperal Received 1 February 1981, ‘Accepted 26 March 1991,