Preemptive Kidney Transplantation Is Associated With Transplantation Outcomes in Children: Results From the French Kidney Replacement Therapy Registry.

BACKGROUND: Kidney transplantation (KT) is the optimal treatment for children with end-stage kidney disease. The aim of this study was to evaluate the impact of preemptive kidney transplantation (PKT) and of pretransplant dialysis duration on graft survival among French pediatric kidney transplant recipients. METHODS: We analyzed all first pediatric kidney-only transplantations performed in France between 1993 and 2012. A Cox multivariable model was used to investigate the association of PKT and pretransplant dialysis time with the hazard of graft failure defined as death, return to dialysis, or retransplant, whichever occurred first. RESULTS: Patients (n = 1911) were included, of which 380 (19.8%) received a PKT. Median time of follow-up was 7.0 y. PKT was associated with a 55% reduction of the hazard of graft failure at any time after KT compared with patients transplanted after dialysis (hazard ratio, 0.45; 95% confidence interval, 0.33-0.62), after adjustment for recipient sex and age, primary kidney disease, donor age and type (living or deceased donor), number of HLA mismatches, cold ischemia time, and year of transplantation. A reduction of the hazard of graft failure was found in PKT whatever the compared duration of dialysis, even when <6 mo and whatever the dialysis modality. Results were similar in multiple sensitivity analyses. CONCLUSIONS: In France, PKT among pediatric patients is associated with a better graft survival when compared with KT after dialysis, even when <6 mo. Based on these findings, we suggest that PKT should be considered as the treatment of choice for children with end-stage kidney disease.

Comparison between citrate and acetate dialysate in chronic online hemodiafiltration: A short-term prospective study in pediatric settings.

BACKGROUND: The use of citrate in chronic hemodialysis to acidify dialysis solutions, in replacement of acetate, began in the 2000's. The purpose of the following study is to determine whether this change represents a better alternative regarding short-term tolerance, efficiency and biocompatibility of chronic renal replacement therapy (RRT) in pediatric patients. METHODS: A monocentric prospective observational study was conducted in the pediatric dialysis department of Nancy (France) between December 1st, 2014 and January 25, 2015 on a cohort of pediatric patients under predilution on-line hemodiafiltration (olHDF). Sessions were analysed during two study periods of 14 days: a first period during which dialysis solutions were acidified using acetate and a second during which solutes were acidified using citrate. These periods were separated by a washout period of 28 days on citrate solution. Each patient served as his own control. RESULTS: Dialysis clinical tolerance seems better under citrate regimen, with no statistical significance. No benefit was brought out regarding the prevention of coagulation accidents in the extracorporeal circuit under citrate regimen. The efficiency of olHDF sessions was similar between periods, both in terms of uremic toxins clearance and medium-molecular-weight molecules (MMWM) removal. The evolution of several biological parameters seemed favourable over the citrate period: increase in pre-dialysis serum bicarbonate, stability of plasma hemoglobin and decrease in erythropoietin resistance index (ERI). However, differences in the variation of these parameters between the two periods were not significant. No severe and/or symptomatic hypocalcemia occurred. CONCLUSION: The use of citrate instead of acetate in dialysis and substitution solutions appears in the short term as a safe alternative for chronic online hemodiafiltration in children.

Reduced Activity of the Aortic Gamma-Glutamyltransferase Does Not Decrease S-Nitrosoglutathione Induced Vasorelaxation of Rat Aortic Rings.

Aims: Gamma-glutamyl transferase (GGT), an enzyme present on the endothelium, is involved in the release of nitric oxide (NO) from S-nitrosoglutathione (GSNO) and in the GSNO-induced vasodilation. Endogenous GSNO is a physiological storage form of NO in tissues while exogenous GSNO is an interesting candidate for compensating for the decreased NO bioavailability occurring during cardiovascular diseases. We investigated in a rat model of human hypertension, the spontaneous hypertensive rat (SHR), submitted or not to high salt diet, whether a decreased vascular GGT activity modifies the vasorelaxant effect of GSNO. Methods: Thoracic aortic rings isolated from male SHR and Wistar Kyoto rats (WKY) aged 20-22 weeks-submitted or not for 8 weeks to a high salt diet (1% w/v NaCl in drinking water) were pre-constricted with phenylephrine then submitted to concentration-vasorelaxant response curves (maximal response: Emax; pD2) to carbachol or sodium nitroprusside to evaluate endothelial dependent or independent NO-induced vasodilation, or GSNO (exogenous NO vasodilation depending from the endothelial GGT activity). GGT activity was measured using a chromogenic substrate in aortic homogenates. Its role in GSNO-induced relaxation was assessed following inhibition of the enzyme activity (serine-borate complex). That of protein disulfide isomerase (PDI), another redox sensitive enzyme involved in GSNO metabolism, was assessed following inhibition with bacitracin. Results: Aortic GGT activity (18-23 µmol/min/mg of tissue in adult WKY) decreased by 33% in SHR and 45% in SHR with high salt diet. Emax and pD2 for sodium nitroprusside were similar in all groups. Emax for carbachol decreased by -14%, reflecting slight endothelial NO-dependent dysfunction. The GSNO curve was slightly shifted to the left in SHR and in SHR with high salt diet, showing a small enhanced sensitivity to GSNO. Involvements of GGT, as that of PDI, in the GSNO effects were similar in all groups (pD2 for GSNO -0.5 to -1.5 following enzymatic inhibition). Conclusion: Hypertension is associated with a decreased aortic GGT activity without decreasing the vasorelaxant effects of GSNO, whose bioactivity may be supplemented through the alternative enzymatic activity of PDI.