Increase in spot urine protein excretion is associated with late kidney graft rejection and predicts rejection phenotype

A noninvasive test that foretells kidney graft rejection before loss of kidney function would be desirable. We hypothesized that an increase in estimated protein excretion rate (ePER) from spot urine samples is associated with graft rejection and predicts rejection phenotype. 151 patients who had undergone first-indication kidney biopsy due to graft dysfunction beyond 3 months after transplant were identified from a national cohort of 616 transplant recipients between 2000 and 2012 (25%). ePER were calculated from spot urine protein-to-creatinine ratios at baseline, 3 months before biopsy (ePER ), and at the time of biopsy (ePER ) and were correlated with histologic biopsy findings. Levels of ePER 3 months before biopsy and at the time of biopsy were greater in 32 patients with antibody-mediated rejection (ABMR) than in 77 patients with T-cell-mediated rejection (TCMR) and 42 patients with other findings (median ePER 912 vs. 320 vs. 232 mg/day/1.73m ; and median ePER 1,672 vs. 356 vs. 268 mg/day/1.73m ; p < 0.001). Receiver operator characteristics (ROC) analyses demonstrated that ePER and ePER had good diagnostic accuracy to discriminate between biopsy specimens showing ABMR vs. those showing TCMR or other histologic findings (area under the ROC curve 0.84, 95% CI 0.75 - 0.93 and 0.89, 95% CI 0.82 - 0.97, respectively; p < 0.001). An increase in ePER before kidney graft dysfunction appears to be associated with graft rejection and predicts ABMR phenotype. .