Longitudinal Epigenome-Wide Analysis of Kidney Transplant Recipients Pretransplant and Posttransplant

Introduction: Kidney transplantation remains the gold standard of treatment for end-stage renal disease (ESRD), with improved patient outcomes compared with dialysis. Epigenome-Wide Association Analysis (EWAS) of DNA methylation may identify markers that contribute to an individual's risk of adverse transplant outcomes, yet only a limited number of EWAS have been conducted in kidney transplant recipients. This EWAS aimed to interrogate the methylation profile of a kidney transplant recipient cohort with minimal posttransplant complications, exploring differences in samples pretransplant and posttransplant.Methods: We compared differentially methylated cytosine-phosphate-guanine sites (dmCpGs) in samples derived from peripheral blood mononuclear cells of the same kidney transplant recipients, collected both pretransplant and posttransplant (N = 154), using the Infinium MethylationEPIC microarray (Illumina, San Diego, CA). Recipients received kidneys from deceased donors and had a mean of 17 years of follow-up.Results: Five top-ranked dmCpGs were significantly different at false discovery rate (FDR) adjusted P <= 9 x 10-8; cg23597162 within JAZF1, cg25187293 within BTNL8, cg17944885, located between ZNF788P and ZNF625-ZNF20, cg14655917 located between ASB4 and PDK4 and cg09839120 located between GIMAP6 and EIF2AP3.Conclusion: Five dmCpGs were identified at the generally accepted EWAS critical significance level of FDR adjusted P (PFDRadj) <= 9 x 10-8, including cg23597162 (within JAZF1) and cg17944885, which have prior associations with chronic kidney disease (CKD). Comparing individuals with no evidence of posttransplant complications (N = 105) demonstrated that 693,555 CpGs (89.57%) did not display any significant differ-ence in methylation (PFDRadj $ 0.05), thereby this study establishes an important reference for future epigenetic studies that seek to identify markers of posttransplant complications.

Automated summary

This study analyzed the DNA methylation of kidney transplant recipients and identified markers associated with the risk of transplant complications. The findings provide an important reference for future epigenetic studies on posttransplant complications.