Abstract / Summary
The oligopeptide transporter PEPT2 is a key transporter mediating the reabsorption of drugs and peptide substances. Unfortunately, there are currently no biomarkers to evaluate the function of the PEPT2 transporter. The aim of this study was to screen and validate endogenous biomarkers of renal tubular PEPT2. Through metabolomics and literature searches, we initially identified two endogenous substrates of PEPT2: carnosine and 5-ALA. By evaluating the uptake of a PEPT2-overexpressing cell line, protein binding rates, and substrate specificity, carnosine was screened as a potential endogenous biomarker for PEPT2. In rats subjected to inhibitor intervention, the level of carnosine significantly increased. In a gentamicin-induced renal injury model, carnosine and creatinine levels changed almost simultaneously. Carnosine is primarily filtered by the glomeruli (with an albumin binding rate of 33%), and subsequently reabsorbed by the PEPT2 transporter, exhibiting appropriate affinity (Km of 59.04μM) and a half-life of 5.5±2.2 hours. These results indicate that carnosine is a suitable endogenous biomarker that can predict renal injury through the detection of its levels.