♦ Background, Objectives, and Methods: The number of patients on chronic peritoneal dialysis (CPD) is increasing rapidly on a global scale. We analyzed the International Pediatric Peritoneal Dialysis Network (IPPN) registry, a global database active in 33 countries spanning a wide range in gross national income (GNI), to identify the impact of economic conditions on CPD practices and outcomes in children and adolescents. ♦ Results: We observed close associations of GNI with the fraction of very young patients on dialysis, the presence and number of comorbidities, the prevalence of patients with unexplained causes of end-stage kidney disease, and the rate of culture-negative peritonitis. The prevalence of automated PD increased with GNI, but was 46% even in the lowest GNI stratum. The GNI stratum also affected the use of biocompatible peritoneal dialysis fluids, enteral tube feeding, calcium-free phosphate binders, active vitamin D analogs, and erythropoiesis-stimulating agents (ESAs). Patient mortality was strongly affected by GNI (hazard ratio per $10 000: 3.3; 95% confidence interval: 2.0 to 5.5) independently of young patient age and the number of comorbidities present. Patients from low-income countries tended to die more often from infections unrelated to CPD (5 of 9 vs 15 of 61, p = 0.1). The GNI was also a strong independent predictor of standardized height (p < 0.0001), adding to the impact of congenital renal disease, anuria, age at PD start, and dialysis vintage. Patients from the lower economic strata (GNI < $18 000) had higher serum parathyroid hormone (PTH) and lower serum calcium, and achieved lower hemoglobin concentrations. No impact of GNI was observed with regard to CPD technique survival or peritonitis incidence. ♦ Conclusions: We conclude that CPD is practiced successfully, albeit with major regional variation related to economic differences, in children around the globe. The
Mortality was low in children with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome, being central nervous system involvement the main cause of death. The best mortality predictors found were central nervous system involvement, hemoglobin, and sodium concentration. Hyponatremia may be a new Shiga toxin-producing Escherichia coli hemolytic uremic syndrome mortality predictor.
TAC, MMF and MP are used in pediatric kidney tx. The cytochrome P450 (CYP)3A5 enzyme appears to play a role in TAC metabolism. The aims of this study were to investigate CYP3A5 polymorphism's effect on TAC dosing and the age dependency of TAC dosing by testing blood concentrations, and the interaction between steroids and TAC during the first year after tx. Genomic DNA was extracted and amplified with specific primers. CYP3A5 alleles were confirmed by direct sequencing of PCR products on an automated AB13100 capillary sequencer. We studied 48 renal transplant patients (age at tx 12±0.5yr, 22 boys) receiving TAC, MMF, MP. Of these, 79% were CYP3A5*3/*3 (non-expressers homozygotes) and 21% were CYP3A5*1/*3 (expressers). TAC trough levels were 7.1±0.4ng/mL in CYP3A5*3/*3 patients and 6.5±0.7ng/mL in CYP3A5*1/*3 group (p=0.03). CYP3A5*1/*3 patients had lower levels of dose-adjusted TAC (36.7±5.8ng/mL/mg/kg/day) to achieve target blood concentration and required higher daily dose per weight (0.21±0.03mg/kg/day) than CYP3A5*3/*3 patients, 72.4±8.0ng/mL/mg/kg/day and 0.13±0.01mg/kg/day (p<0.001). Prepubertal patients with different CYP3A5 polymorphisms required significant higher TAC doses and achieved lower dose-normalized concentration compared with pubertal patients. Both TAC dose and adjusted-dose correlated with daily MP dose in CYP3A5*1*3 (r: 0.4, p<0.03 and r: 0.4, p<0.03) and in CYP3A5*3*3 (r: 0.6, p<0.01 and r: 0.47, p<0.001) patients. CYP3A5 polymorphism performed before tx could contribute to a better individualization of TAC therapy. The higher TAC dose in prepubertal patients and the pharmacological interactions between MP and TAC may not be fully explained by different CYP3A5 polymorphisms.
SummaryBackground and objectives Left ventricular hypertrophy (LVH) is an important end point of dialysis-associated cardiovascular disease. The objective of this study was to evaluate the effect of different pediatric reference systems on the estimated prevalence of LVH in children on chronic peritoneal dialysis (CPD).Design, setting, participants, & measurements Echocardiographic studies in 507 pediatric CPD patients from neonatal age to 19 years were collected in 55 pediatric dialysis units around the globe. We compared the prevalence of LVH on the basis of the traditional cutoff of left ventricular mass (LVM) index (Ͼ38.5 g/m 2.7 ) with three novel definitions of LVH that were recently established in healthy pediatric cohorts.Results Application of the new reference systems eliminated the apparently increased prevalence of LVH in young children obtained by the traditional fixed LVM index cutoff currently still recommended by consensus guidelines. However, substantial differences of LVM distribution between the new reference charts resulted in a marked discrepancy in estimated LVH prevalence ranging between 27.4% and 51.7%.Conclusions Although our understanding of the anthropometric determinants of heart size during childhood is improving, more consistent normative echocardiographic data from large populations of healthy children are required for cardiovascular diagnostics and research.
Allograft function and metabolic effects of four treatment regimens, namely, methylprednisone (MP) standard dose (MP-STD), deflazacort (DFZ), MP-late steroid withdrawal (MP-LSW), and MP-very low dose (MP-VLD), were evaluated in prepubertal patients. MP was decreased by month 4 post-transplantation to 0.2 mg/kg/day in MP-STD and DFZ patients and to <0.1 mg/kg/day in MP-LSW and MP-VLD patients. Starting in month 16 post-transplant, MP was switched to DFZ in the DFZ group and totally withdrawn in the MP-LSW group. Creatinine clearance diminished in the MP-STD and MP-LSW groups from 77 +/- 6 to 63 +/- 6 ml/min/1.73 m(2)and from 103 +/- 5 to 78 +/- 3 ml/min/1.73 m(2), respectively (p < 0.01 and p < 0.001, respectively). Height increased >0.5 SDS only in the MP-LSW and MP-VLD groups. The body mass index and fat body mass for height-age increased only in the MP-STD patients (p < 0.05 and p < 0.01, respectively). Fat body mass decreased in the DFZ group (p < 0.05), total cholesterol and LDL-cholesterol increased in the MP-STD group, while LDL-cholesterol and total cholesterol/HDL-cholesterol ratio decreased in the DFZ group (p < 0.01). Lumbar spine bone mineral density (BMD) for height-age showed an increase in the MP-LSW and MP-VLD groups (p < 0.01). Our data suggest that MP-LSW and MP-VLD strategies improve linear growth, BMD, the peripheral distribution of fat, and preservation of the bone-muscle unit and maintain the normal lipid profile. The MP-LSW patients had a concerning rate of acute rejections and graft function deterioration in prepubertal patients.
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