Aberrant promoter hypermethylation, also known as epigenetics, is thought to be a promising biomarker approach to diagnose malignancies. Kidney repair after injury is a recapitulation of normal morphogenesis, with similarities to malignant transformation. We hypothesized that changes in urine epigenetics could be a biomarker approach during early kidney transplant injury and repair. We examined urine DNA for aberrant methylation of 2 gene promoters (DAPK CALCA) by quantitative methylation specific PCR from 13 deceased and 10 living donor kidney transplant recipients on postoperative day 2 and 65 healthy controls. Results were compared with clinical outcomes and to results of the kidney biopsy. Transplant recipients were significantly more likely to have aberrant hypermethylation of the CALCA gene promoter in urine than healthy controls (100% vs. 31%, p<0.0001). There was increased CALCA hypermethylation in the urine of deceased vs. living donor transplants (21.60 +/− 12.5 vs. 12.19 +/− 4.7 P=0.04). Furthermore, there was a trend towards increased aberrant hypermethylation of urine CALCA in patients with biopsy-proven acute tubular necrosis vs. acute rejection and slow or prompt graft function (mean: 20.40 +/− 6.9, 13.87 +/− 6.49, 17.17 +/− 13.4, P=0.67). However, there was no difference of CALCA hypermethylation in urine of patients with delayed graft function vs. those with slow or prompt graft function (16.9 +/− 6.2 vs. 18.5 +/− 13.7, respectively; P=0.5). There was no aberrant hypermethylation of DAPK in the urine of transplant patients. Urine epigenetics is a promising biomarker approach for acute ischemic injury in transplantation that merits future study.

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