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Recombinant human growth hormone (rhGH) was administered to 13 pediatric renal allograft recipients, ages 7.6 to 17.7 yr, who were 14 to 92 months posttransplant and growth retarded as manifested by either a standard deviation (SD) more negative than -2.00 or a height velocity index of less than 25%. The rhGH was given either daily or thrice weekly (0.375 mg/kg/wk) for a period of 12 to 36 months. Growth velocity increased from 2.7 +/- 2.1 SD for the 12-month period before the initiation of treatment of 6.3 +/- 2.9 SD (P less than 0.00005) and 5.2 +/- 2.9 SD (P less than 0.02) after 12 and 24 months of treatment, respectively. Although individual recipients had improvement in their SD scores, the mean values did not increase despite the increased growth velocity. Except for a 0.5-yr increase over 24 months in two recipients, the bone age did not increase at a rate greater than the increase in chronologic age. Four rejection episodes occurred in two recipients during rhGH treatment--an incidence not greater than that which occurred during a comparable time interval before the initiation of treatment. The calculated creatinine clearance declined from 66 +/- 26 SD mL/min/1.73 m2 at the initiation of treatment to 55 +/- 30 SD mL/min/1.73 m2 at 24 months and 52 +/- 28 SD mL/min/1.73 m2 (P = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

For children with end-stage renal disease, renal transplantation is the ultimate goal because it offers the potential of maximum rehabilitation. In order to evaluate the infectious risk of renal transplantation in patients previously maintained on continuous ambulatory peritoneal dialysis (CAPD) and/or continuous cycling peritoneal dialysis (CCPD), we retrospectively evalauted the clinical course of 44 pediatric patients (mean age 12.0 +/- 5.7 [SD] years) who received 32 cadaver and 16 live-related donor renal grafts after being maintained on peritoneal dialysis for 756 patient-months (mean 17.1 +/- 11.5 months). In the posttransplant period, 25 patients (57%) required dialysis because of acute tubular necrosis or acute rejection. Peritonitis developed in five patients (11%) following transplantation; two were being dialyzed at the time. Exit-site and tunnel infections occurred in nine patients (20%). In all instances, antibiotic treatment and/or catheter removal was curative. Posttransplant ascites developed in 12 patients (27%) and was alleviated by catheter drainage. The catheters were left in situ at the time of transplantation and electively removed when stable graft function was present. The 1- and 2-year actuarial graft survival rate was 65% and 55%, respectively. One patient died in the immediate posttransplant period, which was unrelated to peritoneal dialysis. In conclusion, pediatric patients maintained on CAPD and/or CCPD can be safely transplanted. The potential infectious risks related to peritoneal dialysis can be managed with appropriate management of the catheter and prompt antibiotic therapy. The patient and graft survival rates are comparable to those with patients receiving hemodialysis prior to transplantation. There is no need to limit access to transplantation in children undergoing CAPD and/or CCPD.

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.

Fasting serum cholesterol and serum triglyceride levels were determined in 15 maintenance hemodialysis (MH) and 35 renal transplant (RT) patients. Fourteen of 15 MH patients (93%) had elevated triglyceride levels (greater than 140 mg/100 ml) compared to 11 of 35 RT recipients (31%) (P less than .001). Two of 15 MH patients (13%) had elevated cholesterol levels (greater than 230 mg/100 ml), compared to 18 of 35 RT recipients (51%) (P = .03). In MH patients, a positive correlation was noted between serum triglyceride levels and carbohydrate intake (P = .03). Autopsy material from 12 children who underwent MH or RT was compared to material from 16 age-matched controls; an increased collagenous content of intima, a possible early indicator of coronary artery disease, was noted more frequently (P less than .006) in index patients compared to controls. Our data demonstrate that hyperlipidemia is a frequent finding in pediatric patients treated with MH and RT, and may be associated with premature coronary artery disease.

Aseptic necrosis developed in 11 (6%) of 171 recipients of renal allografts who underwent transplant operations at Childrens Hospital of Los Angeles between February 1967 and August 1977. Pain was the predominant presenting symptom and preceded roentgenographic evidence of aseptic necrosis by as long as seven months. Initial symptoms occurred two months to four years posttransplant. Limited weight bearing and reduction in the dosage of prednisone failed to prevent the progressive destruction of five femoral heads in three patients. Hip replacement led to an amelioration of the symptoms and a resumption of normal activity in each patient. Two patients with involvement of multiple osseous structures have persistent knee and elbow joint pain and effusions, and one of them has required prosthetic replacement of the proximal humerus. No therapy was required for patients with aseptic necrosis of single bones of the hand and foot. There was no statistically significant difference in the total steroid dose received during the first posttransplant year between patients in whom aseptic necrosis developed, and those in whom it did not develop.

Posterior subcapsular cataracts (PSC) were noted in 41 of 69 (60%) recipients of renal allografts. The PSC were noted during the first posttransplant year (Group 1) in 21 (30%) recipients and after the first posttransplant (Group 2) year in 20 (30%) recipients. The dosage of prednisone during the first posttransplant year corrected for patient weight showed a significant correlation with the development of PSC during the first posttransplant year. The severity of the PSC were correlated with time of onset and prednisone dosage. Four recipients in Group 1 required cataract extraction to obtain sufficient vision to facilitate school work.

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.

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.

Serial calculations of glomerular filtration rate were made in 31 pediatric liver transplant recipients surviving more than 1 year. GFR was computed from the Schwartz formula, (cGFR = KL/S Cr), before orthotopic liver transplantation, and at 3-6 monthly intervals thereafter. At the same time points, CsA dose/kg, CsA level, blood pressure, and liver functions were recorded. The mean difference between the pre-OLT cGFR and the most-current cGFR for all patients was -50 ml/min/1.73 m2 (P = less than 0.005). In 17/31 (55%), the current cGFR was less than 80 ml/min/1.73 m2, indicative of renal impairment. The cGFR continued to decrease in 24 patients followed beyond 1 year (26.8 ml/min/1.73 m2 per year decrease, P less than 0.005). More patients with a cGFR less than 80 ml/min/1.73 m2 had outpatient hypertension. There was no correlation of cGFR with CsA levels, CsA dose, or liver function. We conclude that a significant decrease in cGFR is seen in children treated with CsA for more than 1 year, which is progressive in the majority.

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.

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.

Focal segmental and/or global sclerotic glomerular lesions with hyalinosis were noted in three allografts in association with the nephrotic syndrome (NS) and chronic rejection (CR). Similar lesions were absent in eight allografts with CR without NS. Previous reports have stressed the presence of this lesion in allografts with recurrence of the disease entity "idiopathic nephrotic syndrome with focal glomerulosclerosis". Both clinical and pathologic evidence suggest that recurrence was not a factor in the pathogenesis of the lesion in the three allografts with CR and NS. The presence of these lesions in failing allografts may represent the result of CR with associated NS rather than recurrence of the disease entity.