The dilemma of intrauterine diagnosis of congenital renal disease.

The value of improved intrauterine diagnostic capability is unquestioned; however, as with all new technologic advancements, the problems created by this new diagnostic tool need review. This article examines some of the more critical of these difficulties.

Nutritional management of children with chronic renal failure. Summary of the task force on nutritional management of children with chronic renal failure.

Current information on the adaptations to progressive loss of renal function is presented. The assessment of renal function in infants and children using serum creatinine concentration and its derivatives is considered as are various methods for assessment of growth. Children with creatinine clearances less than 50% of normal, who do not have uremic symptoms (and who are not on dialysis), should be ingesting diets providing close to 100% of the RDA for calories with 8% of the calories as protein. Recommendations for nutritional management of children on chronic peritoneal dialysis are also presented.

Protein and energy requirements in children receiving chronic hemodialysis.

Protein and energy requirements were evaluated in 15 children with chronic renal failure. The children were ambulatory and stable, being maintained on hemodialysis and a well-tolerated diet regime. The goals of the study were (1) to approximate the dietary protein and energy levels needed to produce a positive protein balance and (2) to estimate the effect of diet on dialysis requirements. In positive balance periods (18 of 24 periods), the protein intake varied between 0.2 and 0.5 g/cm/day and the energy intake varied between 6.4 and 21.2 kcal/cm/day. A linear relationship existed between the PCR and the protein intake for positive as well as negative protein balance periods. PCR--thus urea generation--was uniformly lower for children in positive balance. Results suggest that a positive balance can be achieved at a protein intake of 0.3 g/cm of statural height and at an energy intake of 10 kcal/cm without an increase in dialysis requirements.

An organ culture model for the study of metanephric development.

A murine whole organ metanephric culture system was designed to study the developmental aspects of mammalian nephrogenesis. Metanephros and ureteric bud were removed from CFI albino mouse embryos at 13.5 +/- 0.4 days gestation, and grown in Dulbecco's modified Eagle's Minimal Essential Medium supplemented with 20 per cent donor bovine serum at 37C in a mixed air--5 per cent CO2 environment. Under the experimental conditions employed, the metanephric explants showed organotypic tubular and glomerular epithelial development. A well-developed proximal tubule with microvilli, and characteristic intracellular organelles and intercellular junctions developed by 72 hours of culture. By 120 hours of culture, unique devascularized glomeruli consisting of parietal and visceral epithelial layers formed. The glomerular visceral epithelial cells formed foot processes and slit pore diaphragms, and produced islands of basement membrane. No endothelial or mesangial elements were present at any stage in organ culture development, indicating that advanced nephrogenesis can occur following initial epithelial-mesenchymal induction despite the absence of vascularization. The whole organ culture model system isolates renal structural development from the influences of perfusion and urine formation. The system thus affords the opportunity to study normal, as well as abnormal mammalian renal development under highly controlled experimental conditions.

Hemolytic uremic syndrome and crescentic glomerulonephritis complicating childhood nephrosis.

Three children with nephrotic syndrome and focal segmental glomerulosclerosis and/or mesangial proliferation on renal biopsy developed the sudden onset of renal failure, microangiopathic hemolytic anemia, and thrombocytopenia. Two of the three children developed crescentic glomerulonephritis and never regained renal function while the third showed no change from his original histologic pattern and also developed chronic renal failure. These cases suggest an association between the lipoid nephrosis-focal segmental glomerulosclerosis group of glomerular diseases and crescentic glomerulonephritis, and may represent an unusual pathway in the evolution of childhood nephrosis.

Comparison of cell-mediated lympholysis and mixed lymphocyte culture in the immunologic evaluation for renal transplantation.

We investigated the relationship between both pre-transplant cell-mediated lympholysis assay (CML) and mixed lymphocyte culture (MLC) and transplant outcome (graft function and survival) in 33 living, related donor renal transplants performed during the past 5 yr. Both assays were excellent predictors of transplant outcome. A positive CML assay was correlated with the occurrence of early acute rejection episodes (p less than 0.005), shortened time to graft dysfunction (serum creatinine greater than 1.5 mg/dl) (p less than 0.001), and poor long-term graft survival (p = 0.07). Similarly, a positive MLC was correlated with acute rejection episodes (p less than 0.005), graft dysfunction (p = 0.001), and poor graft survival (p less than 0.01). To determine the relative prognostic significance of the CML and MLC assays, we compared the correlation of each of them with the occurrence of acute rejection episodes. Under a logistic model of probability, the CML and MLC assays were equally predictive of an early acute rejection episode (p less than 0.01); however, the combination of CML and MLC together improved the accuracy of the prediction of an acute rejection episode by 50%. These results indicate that the CML and MLC assays are independent predictors of transplant outcome and that both tests should be an integral part of the immunologic evaluation of prospective living, related donors for renal transplantation.

Peritonitis in childhood nephrotic syndrome: 1970-1980.

A retrospective review (1970 through 1980) of 351 children with idiopathic nephrotic syndrome disclosed 24 episodes of peritonitis in 19 patients. Twenty-six percent of the patients had more than one episode. Streptococcus pneumoniae was the most common agent (50%), but Escherichia coli remained important (25%). Four cases (16%) were culture-negative. Signs of peritoneal irritation were present in all patients, including the 16 children receiving corticosteroid therapy. No morphological subtype of nephrotic syndrome could be demonstrated to be at increased risk for the development of peritonitis. Significantly decreased IgG levels and an apparent susceptibility to pneumococcal infection among blacks may be important risk factors.

Elevated nephrogenous cyclic adenosine monophosphate to monitor early renal osteodystrophy.

Radiographs, serum chemistries, parathyroid hormone (PTH), and nephrogenous cyclic adenosine monophosphate (cAMP) were evaluated in thirty-two children with normal serum creatinine, chronic renal insufficiency, chronic hemodialysis, and transplantation. Nephrogenous cAMP increases linearly with creatinine, and there is a good correlation (r = 0.89) between immunoreactive PTH (iPTH) and nephrogenous cAMP except for patients with severe renal insufficiency or requiring chronic hemodialysis. Elevated nephrogenous cAMP is evidence for metabolic bone disease earlier than usually recognized. Early measurements of iPTH and nephrogenous cAMP could ensure early therapeutic intervention which might alleviate renal osteodystrophy in chronic renal insufficiency and transplant patients.

Growth acceleration following renal transplantation in children less than 7 years of age.

Of 110 consecutive renal allografts performed at Children's Hospital Medical Center 12 were in 11 patients aged 3 to 7 years. Patient and graft survival and linear growth were evaluated in these 11 children. All 11 are surviving, seven (64%) with functioning allografts 12 to 92 months after transplant. Six of these seven have normal renal function (on alternate day prednisone dose less than 0.7 mg/kg every two days plus daily azathioprine) and all seven have shown catch-up growth, reaching and maintaining normal height for age. An eighth patient, now returned to dialysis, grew from below the third percentile at age 3 years to the 25th percentile at age 8 years, after which renal function deteriorated. Three patients rapidly rejected allografts and have had decreased growth velocity for age. In contrast, although many of the remaining 76 patients who received 98 transplants after age 7 years are growing, none showed accelerated linear growth sufficient to catch up if below the third percentile for age or to cross centile lines if above. Neither the degree of pretransplant bone age retardation nor steroid dose per kilogram accounted for lack of growth acceleration of those more than 7 years of age. Despite small sample size, the growth of renal transplant recipients less than 7 years of age suggests that they are good, and in some ways, favored transplant candidates.

Post-transplant hypertension in the absence of rejection or recurrent disease.

Post-transplant hypertension was reviewed in 86 consecutive renal transplant recipients and occurred in 86 percent. In order to eliminate concomitant causes, those 16 of 86 patients in whom there had never been any rejection episode nor any recurrent diseases were further evaluated for the presence of hypertension. Follow-up period was 1-5 years. All 16 patients were hypertensive in the first postoperative weeks. Nine patients, all with various nephritides, had pre-transplant hypertension, leading to pre-transplant nephrectomies in 5. Post-transplant, all 9 were hypertensive in the first 6 months. By one year post-transplant, blood pressure had normalized in 2 and was controlled on medication in 5 others. In contrast, none of the 7 other patients (all with structural lesions) had pre-transplant hypertension though three had pre-transplant nephrectomies. Only 2 of these 7 patients had post-transplant hypertension, mild in both. The experience demonstrates that prior hypertension correlates positively with post-transplant hypertension, irrespective of native kidney nephrectomies. Patients with previous nephritides carry the greatest risk of becoming hypertensive. Furthermore, the majority of young renal allograft recipients appears to develop hypertension, even in the absence of rejection or recurrent disease.

Mortality of chronic hemodialysis and renal transplantation in pediatric end-stage renal disease.

The long-term mortality of chronic hemodialysis and renal transplantation was analyzed in all children treated for end-stage renal disease at Children's Hospital Medical Center over the pase 8 1/2 years. A total of 216 transplantation or dialysis courses in 120 patients were studied. No patients were excluded from treatment or analysis. Overall actuarial survival was 92% at six months, 90% at 12 months, and 89% at five years. When actuarial survival for each form of treatment was examined, patient survival was 100% at six months and 95% at five years for chronic hemodialysis; 92% at six months and five years for living related transplantation; and 88% at six months and 85% at five years for cadaveric transplantation. We conclude that most children with end-stage renal disease can be kept alive with current treatment programs, and that the mortality of chronic hemodialysis in children is comparable to that of renal transplantation.

Long-term evaluation of chlorambucil plus prednisone in the idiopathic nephrotic syndrome of childhood.

We evaluated the long-term effects of a five to 15-week course of chlorambucil and prednisone in 59 children with idiopathic nephrotic syndrome who had previously received prednisone alone and had had frequent relapses or steroid dependency or resistance. By actuarial analysis of 65 courses of dual therapy followed up for one to 12 years (mean, 5.0), we found that 95 per cent of patients were in remission at one year and 85 per cent at four years. All but two had remissions lasting longer than those induced by steroids alone, and only eight others had one or more relapses after therapy. Life-table analysis of two dosage schedules of chlorambucil at four years showed that 91 per cent of patients on low doses and 80 per cent of those on high doses were still in remission. Although immediate complications were minimal, the potential for long-term toxicity still requires careful selection of patients who receive chlorambucil. Prolonged use of chlorambucil in daily doses above 0.3 mg per kilogram of body weight per day or cumulative doses above 14 mg per kilogram is no longer warranted. Measured in terms of both the immediate and long-term responses, chlorambucil appears to lower the frequency of relapses in idiopathic nephrotic syndrome.

Control of autologous immune complex nephritis. I. Suppression of the disease in the presence of T cell sensitization.

Pretreatment of Lewis and Sprague-Dawley rats with the nephritogenic antigen, Fx1A, in incomplete Freund's adjuvant (IFA) reduced the incidence of autologous immune complex nephritis in rats subsequently challenged with Fx1A in complete Freund's adjuvant (CFA). The suppression was evidenced by a decrease in antibody production, in glomerular deposition of immunoglobulins, and in the incidence of proteinuria, and it was antigen specific. In vitro blastogenesis to Fx1A of lymphocytes from Fx1A-IFA-pretreated animals was normal. Rats pretreated with Fx1A-IFA initially developed a normal antibody response after challenge with Fx1A-CFA, but the response was not sustained. These results indicate that the Fx1A-IFA-induced suppressor mechanism does not inhibit sensitization, but rather modifies specific antibody production.

Complications of essential amino acid hyperalimentation in children with acute renal failure.

The metabolic effects of intravenous hyperalimentation, using an essential amino acid (EAA) and glucose solution, were evaluated in 2 children with acute renal failure. Hyperammonemia and hyperchloremic metabolic acidosis associated with elevated plasma methionine and depressed plasma citrulline, ornithine, arginine, and histidine levels complicated the nutritional therapy. Initial infusion of a complete amino acid (CAA) solution was not associated with these aberrations and reintroduction of a CAA solution after the EAA trial resulted in a progressive amelioration of or complete recovery from these metabolic disturbances. It is likely that the hyperammonemia was due to an arginine deficiency, while excess methionine and presumably sulfate production may have contributed to the hyperchloremic metabolic acidosis in these two children.