Search

Summary Pediatric renal transplantation poses many challenges, yet successful transplantation is the optimum therapy for children with ESRD. The impediments to success are different and of greater magnitude than seen with adults, primarily because of different and problematic disease causes, distinctly different medical and surgical considerations in small children, and what appears to be an enhanced immune response in smaller children. Nevertheless, excellent results can be obtained in pediatric renal transplantation by strict adherence to surgical detail, tight immunosuppressive management, careful integration of urologic reconstructive surgery with the renal transplant, and aggressive fluid management in the small child. 60 Most important to achieving this success is the management of these patients by an integrated and experienced medical, surgical, and anesthesia team.

End-organ resistance to growth hormone and IGF-I in epiphyseal chondrocytes of rats with chronic renal failure. We tested the hypothesis that there is direct end-organ resistance to growth hormone (GH) and IGF-I in chronic renal failure (CRF) independent of circulating inhibitors. Male Sprague-Dawley rats underwent 5/6 nephrectomy and were pair-fed with weight matched (100 g) sham operated controls for two weeks. Rats with CRF had significantly higher serum creatinine and blood urea nitrogen (P < 0.01 in both cases) and gained significantly less weight and length (P < 0.01 in both cases) compared with controls. Epiphyseal chondrocytes were grown in 10% fetal calf serum (FCS). Both CRF cells and control cells maintained chondrogenic phenotypes, and showed immunohistochemical staining with antibodies to collagen II and proteoglycan (aggrecan). Distribution of the cell subpopulations according to cell size (by flow cytometry) and alkaline phosphatase activity of CRF and control chondrocyte cultures were not different. Growth responses of CRF chondrocytes were reduced (P < 0.01) compared with control chondrocytes when grown in 10% FCS and 10% normal rat serum. Under serum free conditions, growth responses of CRF chondrocytes were reduced to GH and IGF-I at concentrations of 10, 30 and 100 ng/ml, and to insulin at 100, 300 and 1,000 ng/ml compared with controls cells (P < 0.01). To show that this resistance is specific for the GH/IGF system, growth responses to fibroblast growth factor and transforming growth factor β1 were studied and showed no difference between CRF and control cells. Thus, the present study provides direct evidence of specific end-organ resistance to GH, IGF-I in CRF chondrocytes in the absence of circulating factors.

To determine whether anemia is important in the pathogenesis of metabolic abnormalities in insulin, amino acid, and lipid metabolism in uremia.Twelve adolescents (15 +/- 1 years of age) undergoing long-term dialysis were studied before and after correction of their anemia by human recombinant erythropoietin at a mean interval of 6 months. Six patients received hemodialysis, and six received continuous-cycling peritoneal dialysis. Insulin sensitivity was measured by the euglycemic clamp technique and insulin secretion by the hyperglycemic clamp technique in these patients.Hematocrit increased from 0.219 +/- 0.006 to 0.344 +/- 0.007 (p0.01). Ferritin concentration did not change significantly (11,252 +/- 356 mg/dl to 785 +/- 226 mg/dl). Serum iron concentration decreased from 134 +/- 13 mg/dl to 83 +/- 11 mg/dl, and percentage saturation decreased from 56 +/- 4 to 41 +/- 5 (p0.05 in both cases). There were no significant changes in weight, height, blood pressure, caloric intake, triceps skinfold thickness, or arm muscular area. There were also no significant changes in serum calcium, phosphate, bicarbonate, albumin, creatinine, or blood urea nitrogen concentration. Insulin sensitivity increased by 33% (p0.01), but insulin secretion did not change significantly. Insulin sensitivity during the euglycemic clamp studies in patients before erythropoietin therapy was lower (145 +/- 10 mg/m2 per minute; p0.01) than published normal values (201 +/- 12 mg/m2 per minute) and was normal after erythropoietin therapy (193 +/- 11 mg/m2 per minute). Insulin secretion was low in patients before erythropoietin therapy (44 +/- 8 microU/ml) compared with published normal values (68 +/- 6 microU/ml) and did not change after erythropoietin therapy (46 +/- 4 microU/ml). Plasma concentrations of branched-chain amino acids and lipids in the patients were compared with values from eight healthy adolescents. Plasma concentrations of valine, leucine, and isoleucine were low before treatment and were normal after 6 months of erythropoietin therapy. Plasma concentrations of triglycerides, total cholesterol, and low-density lipoprotein cholesterol were all high before treatment and were normal after treatment of anemia.Treatment of anemia by erythropoietin reversed insulin resistance as well as amino acid and lipid abnormalities in adolescents undergoing dialysis.

This report describes the serum osteocalcin values in children with mild to moderate, but relatively stable, renal dysfunction followed in the Growth Failure in Children With Renal Diseases Study. This report is derived from data obtained during the control period (6 months) before the initiation of vitamin D therapy. Up to three measurements per patient were obtained. Serum osteocalcin concentration was compared with creatinine clearance (glomerular filtration rate) calculated by the Schwartz formula; with serum concentrations of alkaline phosphatase, parathyroid hormone, and bicarbonate; and with the percentages of the recommended dietary allowances of calories and protein ingested. By standard correlation techniques, there appeared to be an inverse correlation between calculated creatinine clearance and serum osteocalcin concentration, and a direct correlation between serum osteocalcin and parathyroid hormone values. However, when we employed a statistical technique that takes into account repeated measures in the same patient, no correlation was found between calculated glomerular filtration rate and serum osteocalcin concentration, and no direct correlation was found between serum osteocalcin and parathyroid hormone values. The lack of a correlation between calculated glomerular filtration rate and serum osteocalcin values may be due to large fluctuations in the serum osteocalcin concentration, even though renal function is relatively stable.