Improved outcome of pediatric kidney transplantations in the Netherlands -- effect of the introduction of mycophenolate mofetil?

Collaboration of the Dutch centers for kidney transplantation in children started in 1997 with a shared immunosuppressive protocol, aimed at improving graft survival by diminishing the incidence of acute rejections. This study compares the results of transplantations in these patients to those in a historical reference group. Ninety-six consecutive patients receiving a first kidney transplant were treated with an immunosuppressive regimen consisting of mycophenolate mofetil, cyclosporine and corticosteroids. The results were compared with those of historic controls (first transplants between 1985 and 1995, n = 207), treated with different combinations of corticosteroids, cyclosporine A and/or azathioprine. Cytomegalovirus (CMV) prophylaxis was prescribed to high-risk patients in the study group, and only a small proportion of the reference group. The graft survival at 1 yr improved significantly: 92% in the study group, vs. 73% in the reference group (p < 0.001). In the study group 63% of patients remained rejection-free during the first year; in the reference group 28% (p < 0.001). After statistical adjustment of differences in baseline data, as cold ischemia time, the proportion of LRD, preemptive transplantation, and young donors, the difference between study and reference group in graft survival (RR 0.33, p = 0.003) and incidence of acute rejection (RR 0.37, p < 0.001), as the only factor, remained statistically significant, indicating the effect of the immunosuppressive therapy. In the first year one case of malignancy occurred in each group. CMV disease occurred less frequently in the study group (11%) than in the reference group (26%, p = 0.02). As a new complication in 4 patients bronchiectasis was diagnosed. A new consensus protocol, including the introduction of mycophenolate mofetil, considerably improved the outcome of pediatric kidney transplantation in the Netherlands, measured as reduction of the incidence of acute rejection and improved graft surviva

Racial disparities in access to and outcomes of kidney transplantation in children, adolescents, and young adults : results from the ESPN/ARA-EDTA (European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association) registry

Contains fulltext : 167425.pdf (publisher's version ) (Closed access)BACKGROUND: Racial disparities in kidney transplantation in children have been found in the United States, but have not been studied before in Europe. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: Data were derived from the ESPN/ERA-EDTA Registry, an international pediatric renal registry collecting data from 36 European countries. This analysis included 1,134 young patients (aged </=19 years) from 8 medium- to high-income countries who initiated renal replacement therapy (RRT) in 2006 to 2012. FACTOR: Racial background. OUTCOMES & MEASUREMENTS: Differences between racial groups in access to kidney transplantation, transplant survival, and overall survival on RRT were examined using Cox regression analysis while adjusting for age at RRT initiation, sex, and country of residence. RESULTS: 868 (76.5%) patients were white; 59 (5.2%), black; 116 (10.2%), Asian; and 91 (8.0%), from other racial groups. After a median follow-up of 2.8 (range, 0.1-3.0) years, we found that black (HR, 0.49; 95% CI, 0.34-0.72) and Asian (HR, 0.54; 95% CI, 0.41-0.71) patients were less likely to receive a kidney transplant than white patients. These disparities persisted after adjustment for primary renal disease. Transplant survival rates were similar across racial groups. Asian patients had higher overall mortality risk on RRT compared with white patients (HR, 2.50; 95% CI, 1.14-5.49). Adjustment for primary kidney disease reduced the effect of Asian background, suggesting that part of the association may be explained by differences in the underlying kidney disease between racial groups. LIMITATIONS: No data for socioeconomic status, blood group, and HLA profile. CONCLUSIONS: We believe this is the first study examining racial differences in access to and outcomes of kidney transplantation in a large European population. We found important differences with less favorable outcomes for black and Asian patients. Further research is required to address the barriers to optimal treatment among racial minority groups

MSH3 modifies somatic instability and disease severity in Huntington’s and myotonic dystrophy type 1

Huntington’s disease and myotonic dystrophy type 1. A recent Huntington’s disease genome-wide association study found rs557874766, an imputed single nucleotide polymorphism located within a polymorphic 9 bp tandem repeat in MSH3/DHFR, as the variant most significantly associated with progression in Huntington’s disease. Using Illumina sequencing in Huntington’s disease and myotonic dystrophy type 1 subjects, we show that rs557874766 is an alignment artefact, the minor allele for which corresponds to a three-repeat allele in MSH3 exon 1 that is associated with a reduced rate of somatic CAG CTG expansion (P = 0.004) and delayed disease onset (P = 0.003) in both Huntington’s disease and myotonic dystrophy type 1, and slower progression (P = 3.86 10 7) in Huntington’s disease. RNA-Seq of whole blood in the Huntington’s disease subjects found that repeat variants are associated with MSH3 and DHFR expression. A transcriptome-wide association study in the Huntington’s disease cohort found increased MSH3 and DHFR expression are associated with disease progression. These results suggest that variation in the MSH3 exon 1 repeat region influences somatic expansion and disease phenotype in Huntington’s disease and myotonic dystrophy type 1, and suggests a common DNA repair mechanism operates in both repeat expansion diseases.UK DementiaResearch Institute/[]//Reino UnidoMedical Research Council/[MR/L010305/1]/MRC/Reino UnidoEuropean Union’s Seventh Framework Programme/[2012-305121]/FP7 2007-2013/Unión EuropeaRosetrees Trust/[JS16/M574]//Reino UnidoUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA