Utility of urinary organic anion transporter 5 as an early biomarker of obstructive nephropathy

Abstract

Ureteral obstruction is a relevant cause of kidney damage. The traditional parameters used in clinical practice for the detection of renal injury are insensitive and non-specific for the diagnosis of obstructive renal disease. The organic anion transporter 5 (Oat5) is a carrier expressed exclusively in the kidney. In this study, the Oat5 urinary excretion (Oat5u) was evaluated as a potential biomarker of obstructive nephropathy, comparing it with traditional markers of renal function and with neutrophil gelatinase-associated lipocalin in urine (NGALu), a more recent biomarker of renal pathology. Bilateral ureteral obstruction (BUO) was induced in male Wistar rats, by complete ligation of ureters for 1 hour (BUO1), 2 hours (BUO2), 5 hours (BUO5), or 24 hours (BUO24). After 24 hours of ureteral releasing, urea and creatinine plasma concentrations, creatinine clearance, urinary total proteins, urinary glucose, and alkaline phosphatase activities in urine were evaluated. Oat5 and NGAL levels were assessed in urine samples by immunoblotting. All parameters of renal function were altered in the BUO24 and some also in BUO5, while the Oat5u increased in all of the experimental groups analyzed. After a long time of ureteral obstruction (BUO24), the urinary excretion of Oat5 markedly increased, in parallel with the alteration in the other parameters evaluated. Nevertheless, in BUO1 and BUO2, Oat5u appeared as the only parameter modified. Therefore, Oat5u could be proposed as a novel early biomarker of ureteral obstruction, with the additional potential to inform about the severity of the obstructive injury suffered by the kidney.