Citations

Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium ( n Stage1 : 111,666; n Stage2 : 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea ( PPM1J , EDEM3, ACP1, SPEG, EYA4, CYP1A1 , and ATXN2L ; P Stage1 <3.7×10 −7 ), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 ( P =5.4×10 −8 by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of acp1- and sos2 -knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation.

Aims To examine the need for minimal diagnostic criteria for post-transplant lymphoproliferative disorders (PTLD) in children, we sought to determine the rate of incidental Epstein-Barr virus (EBV)-positivity in tissues from organ transplant recipients (OTR). Methods EBV in situ hybridisation (ISH) was done retrospectively on tissue from 34 paediatric autopsies of OTR and paediatric tonsillectomy specimens from non-OTR (96) and OTR (6). Patients with a history of PTLD were excluded from both data sets. Results EBV-positivity was found incidentally in 2/34 autopsy cases (5.9%). Median time from transplant to death for all patients was 12.8 months (range 0.1–153 months). Median time between transplant and death in EBV-positive cases was 34 months. EBV was positive in 26/102 tonsils (25%). Among tonsils from OTR, 4/6 (67%) were EBV-positive. Conclusions These findings reinforce the need for strict morphological and clinical criteria, other than EBV-positivity, when diagnosing PTLD in the paediatric population.