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Objective: Recombinant human growth hormone (rhGH) has been used to improve the growth retardation associated with chronic renal insufficiency (CRI) and end-stage renal disease. We determined the incidence of one of four targeted adverse events (AEs): malignancy, slipped capital femoral epiphysis (SCFE), avascular necrosis (AN), and intracranial hypertension (ICH)., Study Design: During a 6.5-year period, we prospectively assessed patients enrolled in the CRI, dialysis, and transplant registries of the North American Renal Transplant Cooperative Study. The availability of an untreated control population facilitated determining whether or not there was the association between the AE and rhGH treatment., Results: Of the targeted AE, the only significant relation with rhGH treatment was the presence of ICH in patients with CRI; however, in all 3 instances, ICH occurred 2, 50, and 1131 days after discontinuation of rhGH. Considering that the mechanism of ICH in rhGH-treated patients is thought to be increased CSF production, rhGH probably had no role in the development of ICH in at least 2 of the 3 patients with CRI. A number of nontargeted AE were identified that have been associated with rhGH treatment in patients without renal disease. The incidence of glucose intolerance, pancreatitis, progressive deterioration of renal function, acute allograft rejection, and fluid retention were not more frequent in those receiving rhGH treatment compared with the control population., Conclusions: This report validates the importance of a control population in ascribing AE to any therapeutic intervention. Previously identified AE associated with rhGH treatment are infrequent in patients with CRI and end-stage renal disease.

Objective: To evaluate post-transplant outcomes for patients treated with human growth hormone (rhGH) during the course of chronic renal insufficiency (CRI)., Study Design: Patients (the "cohort" group) were identified who had been enrolled in 2 controlled studies to determine the efficacy and safety of rhGH in growth-retarded children with CRI and were subsequently enrolled in the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) and received a renal transplant. Patient survival, graft survival, time to first acute rejection episode, causes of graft failure, adverse events, and serial growth data from transplant to 60 months were evaluated. Data from the cohort group of 102 patients were compared with data from 4913 primary transplants from "other NAPRTCS" recipients (the "control" group)., Results: No significant difference was seen in patient survival or graft survival, incidence of acute rejection episode, or time to first rejection episode between the cohort and control groups. No specific adverse events were attributable to previous rhGH treatment. Only 2 patients had post-transplant lymphoproliferative disease in the cohort group, with no other malignancies reported. The mean height z scores in the cohort group at baseline and 60 months after transplant were -1.92 and -1.90, and the Deltaz score at 60 months was +0.20 compared with the control group (-1.88 and -2.10)., Conclusions: Treatment of growth-retarded patients with CRI does not adversely affect graft function after renal transplantation. "Catch-down" growth does not occur after renal transplantation.

Objective: To evaluate growth response and renal allograft measures after recombinant human growth-hormone (GH) treatment in pediatric renal transplant recipients., Study Design: Data on GH-treated children in the National Cooperative Growth Study (NCGS) database were linked to the database of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Data were analyzed for growth rate, graft survival, graft function, acute rejection, and adverse events. Data on 2390 transplant recipients in the NAPRTCS who had at least 24 months of graft function were used in the comparisons., Results: Fifty-nine patients were treated with GH after renal transplantation. One-year growth data were available for 42 of these; 2-year, for 31; and 3-year, for 13. Growth velocity increased from 2.47 +/- 1.83 cm/yr to 7.17 +/- 2.97 cm/yr after 1 year. Year-2 and -3 growth rates were 5.93 +/- 2.29 cm/yr and 6.31 +/- 2.32 cm/yr. Height standard deviation score immediately after transplantation was -3.26 +/- 1.44 and at the initiation of GH was -3.59 +/- 1.15; it increased to -3.18 +/- 1.06 at year 1 and to -3.16 +/- 0.92 at year 2 and was -3.31 +/- 1.00 at year 3. Five-year graft survival was 80% in the GH cohort and 85% in the NAPRTCS cohort. Acute rejection ratio was 1.44 and 1.43 episodes per patient in the GH and NAPRTCS cohorts, respectively. Calculated creatinine clearance at 6 years was 68 and 63 ml/min per 1.73 m2, respectively., Conclusions: Growth hormone increase growth velocity for up to 3 years without an apparent decrease in graft survival or renal function, and no relation between GH therapy and acute rejection is seen. A randomized, prospective study to evaluate further the safety and efficacy of this promising therapy is required.

Objectives: The impact of a pause in treatment with recombinant human growth hormone (rhGH) during the course of chronic renal insufficiency (CRI) once target height (50th percentile for mid-parental height) is reached and the impact of cessation of rhGH treatment after successful renal transplantation were evaluated. Prepubertal patients with CRI included in a multicenter, randomized, double-blind, placebo-controlled trial who either reached target height or received a renal transplant, or both, were included in this report. Patients in the placebo group may have initiated pubertal development at the time rhGH treatment was begun., Study Design: Growth velocity (measured in centimeters per year) and standardized height score (SDS) in 22 patients who had a pause in rhGH therapy after attainment of target height were evaluated serially before and after the pause, and 30 patients, 4 of whom were also included in the pause group, who discontinued rhGH therapy at the time of transplantation were followed as long as 68 months after transplantation., Results: Six of twenty-two patients (two of whom subsequently underwent transplantation) continued with the pause in treatment for a mean (+/-SD) duration of 25.5 +/- 26.9 months (group 1), and 16 of 22 resumed rhGH therapy after pausing for a mean (+/-SD) of 9.0 +/- 4.6 months (group 2). The mean (+/-SD) growth velocity during the pause in group 1 was 5.1 +/- 1.8 cm/yr and in group 22.7 +/- 1.7 cm/yr. After reinstitution of rhGH in group 2, the mean (+/-SD) growth velocity increased to 7.2 +/- 1.7 cm/yr. The mean (+/-SD) height SDS in the 30 patients who discontinued rhGH therapy at the time of transplantation was -2.8 +/- 0.9 at baseline (initiation of rhGH therapy), -1.6 +/- 1.3 at the time of transplantation, and -1.7 +/- 1.2 at last follow-up. The mean (+/-SD) growth velocity was 5.1 +/- 4.7 cm/yr after transplantation, and the mean (+/-SD) delta (delta) height SDS was -0.07 +/- 0.5 at last follow-up., Conclusions: A pause in rhGH treatment in children with CRI after attainment of target height leads to maintenance of height SDS in 27% and a marked reduction in growth velocity, requiring reinstitution of rhGH therapy, in 73%; discontinuing rhGH treatment at the time of transplantation does not result in substantive posttransplantation "catch down" growth.

Objective: To determine whether treatment with recombinant human growth hormone (rhGH) enhances growth rate in growth-retarded children with chronic renal failure., Design: One hundred twenty-five prepubertal growth-retarded children with chronic renal failure were randomly assigned to receive either rhGH (n = 82) or placebo (n = 43) for 2 years., Setting: The study was undertaken at 17 pediatric nephrology centers in the United States., Measurements: Growth rate, standardized height, bone age, fasting and 2-hour postprandial glucose and insulin levels, biochemical values, and insulin-like growth factor I and anti-growth hormone antibody levels were evaluated serially during the 2-year study period., Results: Standardized height increased from -2.94 to -1.55 in the rhGH group after 24 months of treatment, and decreased from -2.82 to -2.91 in the placebo group (p < 0.00005). Patients in the rhGH group who completed 24 months of study (n = 55) had a greater growth rate during the first year (10.7 +/- 3.1 cm/yr) than during the second year (7.8 +/- 2.1 cm/yr) of treatment. These growth rates were significantly greater than those in the placebo group (n = 27) in the first (6.5 +/- 2.6 cm/yr) and second (5.5 +/- 1.9 cm/yr) years (p < 0.00005 for both years). The mean delta height age minus the delta bone age was positive in the rhGH group, suggesting improved final height potential. There was no significant difference in the change in calculated creatinine clearance over baseline values in the rhGH group from that in the placebo group after 24 months of study (p = 0.63). Mean fasting and postprandial insulin values were elevated at 12 months but not at 24 months in the rhGH-treated patients. Mean fasting and 2-hour postprandial glucose values at 24 months were not significantly elevated over baseline values in either group., Conclusions: Growth rate and standardized height were significantly increased in growth-retarded prepubertal children with chronic renal failure when rhGH was used. The acceleration in growth was not associated with undue advancement of bone age. No clinically significant side effects were associated with rhGH treatment. The use of rhGH in growth-retarded children with chronic renal failure may facilitate the achievement of the inherent growth potential of such children.

The Growth Failure in Children With Renal Diseases Study, a double-blind, multicenter clinical trial with 108 children entered into the control period over 4.3 years of patient enrollment (December 1984 to April 1989), is being extended for 3 years (December 1988 to December 1991) to provide the time needed to accrue additional patients, aged between 1 1/2 and 10 years, with glomerular filtration rates of 20 to 75 ml/min/1.73 m2. The study design of randomization to two treatment arms (1,25-dihydroxyvitamin D vs dihydrotachysterol) requires a total of 108 patients with a minimum of 6 months of treatment to test the long-term effectiveness and safety of 1,25-dihydroxyvitamin D, an essential part of the therapeutic regimen for children with chronic renal insufficiency. The frequent longitudinal assessments of nutrition and growth in children with chronic renal insufficiency can better define the natural history of renal disease and its influence on growth. Similar data in the treatment period will define the impact of treatment with 1,25-dihydroxyvitamin D3 versus dihydrotachysterol on this natural history. Linear growth must be observed long enough (6 to 12 months minimum) to permit valid quantitation and comparison of the two vitamin D treatment arms, the multiple confounding variables that affect growth (e.g., steroid therapy, diabetes mellitus, prior vitamin D treatment) must be rigorously excluded or controlled, and the assignment of patients to the two groups must be random. These controls--sufficient study duration, sufficient patient numbers, and randomization--should eliminate extraneous sources of variation, including seasonal periodicity. This carefully developed, double-blind clinical trial with multiple participating centers and an effective organizational structure is coming close to achieving the goals of the study. An explosion of data regarding the natural history of chronic renal insufficiency and its treatment with vitamin D metabolites will be forthcoming at the conclusion of the study.

We examined the clinical significance of hepatitis Be antigenemia in 36 HBsAg positive pediatric dialysis and renal transplant patients. One hundred twenty-seven sera were tested for HBeAg and anti-HBe. Seventy-three sera (57%) from 29 patients (81%) contained HBeAg. The presence of HBeAg was associated with an increased titer of HBsAg (P < 0.005) and with the presence of the HBsAg carrier state (P < 0.001). HBeAg was found in 40% of specimens taken from dialysis patients, and in 70% of specimens from transplant patients (P < 0.001). No serum contained anti-HBe, although 28 of 29 sera (97%) tested had antibody to HBcAg. No association was found between the presence of HBeAg and serum aminoleucine transferase levels or the histologic evidence of chronic active hepatitis. Fifteen HBeAg negative sera from patients persistently positive for HBsAg were tested for HBV-specific DNA polymerase activity; 7 (47%) had significant activity. Since both HBeAg and DNA p are indicators of infectivity, many HBeAg negative sera from immunosuppressed HBsAg carriers may be infectious.

The course of 54 patients (35 boys and 19 girls) with end-stage renal disease resulting from obstructive uropathy was reviewed. The mean age at the initial sign of obstructive uropathy was 3.5 years. Twenty-two patients (41%) manifested evidence of obstructive uropathy during the first year of life. The mean age at the time of onset of ESRD (dialysis) was 12.2 years and was similar in boys and girls. The mean time interval between the first sign of obstructive uropathy and the initiation of dialysis was nine years. Fourteen patients operated upon at less than one year of age developed ESRD one to 20 years (mean ten years) following their initial surgery. Progression to ESRD occurred despite appropriate surgical management, including corrective as well as diversionary urologic procedures. However, because the patients were selectively referred for care of ESRD, no assessment of the incidence of ESRD caused by obstructive uropathy was possible. The data indicate that prolonged follow-up periods are necessary to assess the ultimate outcome of renal function in young patients with obstructive uropathy. Despite early intervention and intact renal function for many years during childhood, progression to ESRD may occur.

Orally administered calcium carbonate was evaluated as a phosphate binding agent in 15 children, ages 0.6 to 17.2 years, receiving maintenance dialysis. Changes in plasma aluminum concentration were assessed after discontinuation of treatment with aluminum-containing gels. The mean daily dose of calcium carbonate was 5.1 +/- 2.5 gm (384 +/- 315 mg/kg/day), and correlated inversely with body weight (r = 0.72, P less than 0.01) and age (r = 0.71, P less than 0.01). Mean serum calcium, phosphorus, and bicarbonate values were unchanged throughout the study. Plasma aluminum concentration fell from 90 +/- 51 to 34 +/- 22 micrograms/L (P less than 0.005). Dietary phosphorus intakes were 44 +/- 21 and 42 +/- 19 mg/kg/day during the control period and at the end of the study, respectively. Transitory hypercalcemia was the only side effect in 92% of the patients. In none of the patients did uncontrolled hyperphosphatemia, metabolic alkalosis, diarrhea, or symptoms or signs of hypercalcemia develop. Our data indicate that calcium carbonate is an effective phosphate binding agent in children receiving dialysis, and should be used in lieu of aluminum-containing gels in young children with renal failure.

The clinical courses in 10 pediatric patients undergoing CAPD for 15.0 +/- 2.8 months and subsequently CCPD for 9.3 +/- 3.2 months were evaluated. During CAPD patients received four or five daily exchanges, and during CCPD five 2-hour nocturnal cycles over 10 hours plus a diurnal dwell. The only significant biochemical difference during CAPD compared with CCPD was the serum creatinine concentration (9.7 +/- 1.0 mg/dl vs 10.8 +/- 0.9 mg/dl, P less than 0.01). The peritonitis rate was one episode every 10.7 patient months during CAPD, compared with one episode every 8.5 patient months during CCPD. There were 21 episodes of exit site infection during CAPD versus 17 during CCPD. Mechanical complications included five ventral hernias in three patients and six peritoneal leaks in three patients during CAPD; two patients had two hernias and two patients had two peritoneal leaks during CCPD. Our results indicate adequate control of the biochemical abnormalities of uremia with CCPD, with the exception of the serum creatinine concentration.

We studied the effect of recombinant human growth hormone treatment on five boys, aged 4.6 +/- 1.8 years, who had chronic renal failure secondary to congenital renal diseases (mean creatinine clearance (+/- SD): 18.3 +/- 6.3 ml/min/1.73 m2 (0.32 +/- 0.11 ml/sec/1.73 m2]. Patients received 0.125 mg/kg of growth hormone three times per week for 1 year. Before beginning treatment, the children had a mean annual growth velocity of 4.9 +/- 1.4 cm/yr (range 3.0 to 6.3 cm/yr), with a mean standard deviation score for a height of -2.98 +/- 0.73 (range -2.16 to -3.59). At the end of therapy, the mean growth velocity had increased to 8.9 +/- 1.2 cm/yr (range 7.5 to 10.7 cm/yr), and the mean height standard deviation score improved to -2.36 +/- 0.83 (range -1.15 to -3.18). Bone age advancement was consistent with the period of growth. Routine laboratory determinations, including results of glucose tolerance testing, did not vary significantly from pretreatment levels. These preliminary data indicate that growth-retarded children with chronic renal failure can respond to exogenous growth hormone therapy with a marked acceleration in growth velocity.

Experience with the prenatal diagnosis and management of four cases of congenital renal abnormalities is presented. Neither prenatal intervention nor early delivery was indicated in any of these patients. The current enthusiasm for aggressive management of fetal renal abnormalities may underestimate difficulties in prenatal diagnosis and overestimate the potential benefits of early intervention.

Eighteen patients with corticosteroid-resistant nephrotic syndrome developed end-stage renal disease and received one or more renal allografts. The lesion of focal segmental glomerulosclerosis and/or of focal glomerular obsolescence was demonstrable in the native kidneys of each patient. Following transplantation, nephrosis developed in three recipients. Two recipients developed nephrosis at two weeks and nine months posttransplant in association with rejection; the lesion of FGS was present in association with chronic rejection. Only one recipient developed recurrence of nephrosis and FGS unrelated to rejection. This was manifested by immediate onset of nephrosis in two successive allografts and histologic evidence of the lesion of FGS. The immediate recurrence in successive allografts suggests a circulating factor responsible for the renal lesion in this patient and indicates a separate etiology for a small number of patients with corticosteroid-resistant nephrosis and FGS.

Hypertension persisted for longer than 6 mo or developed de novo after the first month following transplantation in seven of 77 pediatric recipients of renal allografts; concomitantly there were an elevation of PRA and renal angiographic abnormalities. In two of the four patients who developed RAS there was evidence of diminished allograft function. Successful correction of the stenotic lesion in these two recipients resulted in a return of the blood pressure, PRA, and biochemical function of the allograft to normal. Unsuccessful attempts at surgical repair led to loss of the allograft in the other two patients with RAS. Intrarenal vascular and/or parenchymal lesions were evident in the other three recipients with hypertension. Although an explanation was not apparent, subclinical rejection was hypothesized. Treatment effected reduction of the hypertension in these three patients and no deterioration of allograft function was observed for periods of 5, 34, and 38 mo, respectively. Renal angiographic studies and determinations of PRA are recommended in any pediatric recipient of an allograft who develops hypertension after the first month following transplantation or has hypertension which persists for longer than 6 mo after transplantation.

Six children, from 1.3 to 18 years of age, with severe hypertension associated with the hemolytic uremic syndrome, periarteritis, and renal transplant rejection received minoxidil, an antihypertensive agent, for three to 36 weeks. All had severe hypertension resistant to oral antihypertensive medications; five required frequent intravenous diazoxide therapy prior to minoxidil therapy. The mean pretreatment systolic and diastolic blood pressures were 176 and 117 mm Hg, respectively. Following treatment, the mean systolic and diastolic blood pressures were 133 and 82 mm Hg, respectively. Concomitant antihypertensive medications were decreased in all six patients once optimal blood pressure control was obtained. The initial dosage of minoxidil was 0.1 to 0.2 mg/kg/day; maximal dosage for blood pressure was 0.3 to 1.4 mg/kh/day. Major complications of therapy were fluid retention and hirsutism. Transient asymptomatic pericardial effusions occurred in two patients. Three patients on prolonged minoxidil therapy had persistent increases in right ventricular end diastolic diameters. Minoxidil is an effective oral antihypertensive agent for treatment of severe hypertension in pediatric patients. Avoidance of fluid retention is mandatory to prevent congestive heart failure.

Two important criteria for successful end-stage renal disease therapy in children are achievement of optimal growth and possession of a well-functioning renal transplant. We describe eight children with accelerated post-transplant growth. Accelerated and even catch-up growth was achievable if the transplant occurred at an early age (less than 9 years), the daily dose of prednisone was low (less than or equal to 0.24 mg/kg/d), and renal function was excellent (creatinine clearance greater than or equal to 89 mL/min/1.73 m2). However, the benefit to growth of transplanting a kidney in young children may be offset by reduced cadaver graft survival in children younger than 6 years. To study whether the less favorable graft survival was attributable to an increased immunologic responsiveness in the younger child, we examined three tests of nonspecific immune responsiveness, each of which, when increased, may indicate a propensity toward rejection: total T cell absolute number, T helper/suppressor ratio, and spontaneous blastogenesis. Each measurement was significantly increased in 20 uremic children 5 years old or younger, compared with 81 children 6 to 23 years of age. These data suggest that improved growth may be attained by transplanting a kidney in the young child with end-stage renal disease, but the young child may be at increased risk for rejection. This hypothesis suggests that for optimal rehabilitation, strategies should take into account the unique needs of the young child.

Serum aluminum concentrations were measured in 16 children undergoing continuous ambulatory peritoneal dialysis after 7.9 +/- 2.1 (mean +/- SE) and 16.6 +/- 2.3 months of therapy, when the estimated simultaneous oral Al intake from Al hydroxide gels was 98 +/- 20 and 104 +/- 32 mg/kg/day, respectively. Serum Al concentrations were 55.2 +/- 11.4 and 59.8 +/- 10.4 micrograms/L, respectively, compared to 8.2 +/- 1.1 micrograms/L in normal children (P less than 0.001). Serum Al levels correlated with oral Al intake (r = 0.86, P less than 0.001) and inversely with body weight (r = -0.68, P less than 0.01) and age (r = -0.67, P less than 0.01). The youngest patient with the highest serum Al concentrations (208 and 174 micrograms/L) and greatest Al intake (310 and 192 mg/kg/day) had bone biopsy features characteristic of aluminum-related bone disease. Thus, higher aluminum intake per kilogram body weight given to young children is likely to raise the serum Al levels and increase the risk of osteomalacia. Aluminum-containing antacids should be used with caution in infants and young children with renal failure.

Evaluation of 75 cadaver donor retransplants revealed that the primary factor influencing allograft survival is patient responsiveness as reflected by sensitization with preformed cytotoxic antibodies. Actuarial allograft survival rates for nonpresensitized (less than 5%) and moderately presensitized (5 to 50%) recipients were significantly (P less than 0.01) better than those of highly presensitized (greater than 50%) recipients. Although HLA A&B antigen histocompatibility did not have a statistically significant effect on retransplant outcome, it appeared to influence allograft survival in the highly presensitized recipient. An approach to the management of children who lose an initial or subsequent allograft is indicated by these data.

Serial HB Ag determinations were obtained on 62 children undergoing hemodialysis during a 31/2-year period. Thirty six (58%) of the patients had atleast one positive HB Ag determination (titer larger than 1:8) either during the period of dialysis or within 2 months after transplantation. Of the children who became HB Ag positive during the period of dialysis, 89% demonstrated hepatitis B antigenemia during the initial 6 months of dialysis. Becuase of the temporal relationship between the development of HB Ag positivity and the duration of dialysis, contamination of equipment was proposed as a contributing source for transmission of HB Ag. Although 67% of the patients who were HB Ag positive during dialysis developed biochemical evidence of hepatic dysfunction, only two patients had clinical manifestations. The incidence of hepatic involvement appeared to be related to age; only one of nine children less than 12 years of age had evidence of hepatic disease. Intermittent persistence of HB Ag for periods larger than 3 years was observed. Both the incidence and persistence of HB Ag indicate the need to prevent its acquisition by pediatric patients undergoing hemodialysis.

In 93 children, end-stage renal disease was treated with the new dialytic methods of continuous ambulatory peritoneal dialysis (CAPD) or continuous cycling peritoneal dialysis (CCPD) over 5 years. Modality survival rates at 36 months with CAPD, CCPD, or both were 20%, 93%, and 87%, respectively. Use of CCPD as the primary dilaytic method increased during the study period. The peritonitis rate was one episode per 11.8 patient treatment months and was similar with both CAPD and CCPD. Gram-positive organisms were cultured in 34% of these episodes of peritonitis. Staphylococcus aureus peritonitis was associated with a recurrence rate of 40% and led to catheter replacement in 45% of the episodes. Peritoneal membrane failure necessitating switching to hemodialysis was related to peritonitis in three patients. Of the 74 peritoneal catheters that required replacement, 70% were infected. Serial serum levels of urea nitrogen, potassium, calcium, phosphorus, albumin, and alkaline phosphatase remained stable, whereas serum creatinine level rose slightly over time. Episodes of hyperkalemia, hypercalcemia, and hyperphosphatemia were observed at a frequency of one episode per 12.2, 4.6, and 2.5 treatment months, respectively. Blood transfusions were required in once per 1.5 and 3.3 treatment months in seven anephric patients and in 35 patients with their own kidneys, respectively (P = 0.05). In prepubertal patients who received CAPD or CCPD for greater than 1 year, little or no improvement in growth occurred in relationship to either chronologic or bone age.

Five anemic, transfusion-dependent patients aged 12 to 18 years, who had end-stage renal disease (mean hematocrit value 22 +/- 0.31%) and were on a regimen of peritoneal dialysis, were treated with recombinant human erythropoietin (rHuEpo), which was self-administered at home by subcutaneous injections thrice weekly at an initial dosage of 150 U/kg. All patients had an increase in the reticulocyte count and hemoglobin concentration, and none required further transfusions. The hematocrit level rose to a mean of 33.04 +/- 1.86% within 3 weeks of rHuEpo therapy, and the dosage was adjusted to keep the hematocrit level between 32% and 38% indefinitely. Currently four of these patients require only one dose a week to sustain the hematocrit level. No antibodies to the rHuEpo were formed. Three patients had an exacerbation of hypertension, which required an adjustment in antihypertensive therapy. No other side effects were noted. The results demonstrate that rHuEpo is effective in correcting the anemia of end-stage renal disease, thereby eliminating the associated clinical symptoms and the need for further blood transfusions.

Administration of anticonvulsant medication to recipients of cadaver renal allografts appears to be associated with decreased allograft survival. The one-and two-year actuarial graft survival rates for 20 index grafts was significantly lower than for 92 control grafts. Since phenobarbital and diphenylhydantoin increase the metabolism of corticosteroids, it is proposed that renal allograft recipients receiving these anticonvulsants may have ineffective immunosuppression, leading to a higher incidence of graft failure.