Urinary dipeptidyl peptidase-4 is a useful marker for tubulitis, and it is released from the tubular cells of kidney transplant recipients

Background Biomarkers are needed to diagnose kidney rejection in transplant recipients. We evaluated whether dipeptidyl peptidase-4 (DPP-4) could serve as a biomarker of rejection. Methods We determined DPP-4 concentrations and enzymatic activities in serum and urine, as well as DPP-4 expression in 49 kidney biopsy samples from 28 kidney transplant recipients. This study was approved by the ethical standards of the institutional research committee and comply with Helsinki declaration. All patients provided their informed consent. Donors were not from prisoners and were not paid or coerced. Results Serum and urinary DPP-4 activities closely correlated with DPP-4 concentrations, but were suppressed by DPP-4 inhibitors. Urinary DPP-4 concentrations increased with acute T cell-mediated rejection (ATCMR; p = 0.030) and higher Banff t and i scores ( p < 0.001), and correlated with urinary protein/creatinine ratios ( r = 0.450), and inversely with estimated glomerular filtration rate ( r = − 0.604). The area under the receiver operator characteristics curves for urinary DPP-4 concentrations with either Banff t3 or i3 scores were 0.811 (95% confidence interval: 0.687–0.934). The expression of DPP-4 in renal tubular cells was decreased in patients with ATCMR and higher in those with Banff t, i, ct, ci, ah, and ti scores, but was not associated with interstitial fibrosis/tubular atrophy. Conclusions We speculated that ATCMR leads to DPP-4 release from tubular cells into urine, resulting in a decrease in tubular cell expression. If so, then ATCMR would induce the elevation of urinary DPP-4 and could therefore serve as a biomarker of tubulitis.