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.

Hepatic and renal expression of Oatp1 in obstructive uropathy. First detection of Oatp1 in urine, a potential biomarker

“…BUO5 and BUO24 kidneys denoted interstitial fibrosis, tubular dilatation, cellular desquamation and cellular debris, as previously reported in this experimental model. [16][17][18][19] The changes of tubules integrity were significantly different in comparison with sham kidneys as indicated by tubular injury scores.…”

“…Urine samples from BUO animals were run on each gel with a reference sample of sham renal apical membranes, and were relativized to urinary creatinine, as previously reported. 16,17,20 To determine if the urinary excretion of Oatp1 could also be postulated as an early biomarker of obstructive nephropathy, two additional experimental groups with shorter time of ureteral obstruction were included (BUO1 and BUO2). Although no differences in Oatp1 u were found between BUO1, BUO2 and BUO5 groups (increases of ~20%), in BUO24 the urinary excretion of Oatp1 was significantly higher (around 70%) (Figure 6B).…”

“…Our research group has experience in working with experimental models of obstructive nephropathy. 16,17 Previous studies showed that ureteral obstructions are associated with the decrease in renal expression of several organic anion transporters. 16,17 Moreover, it has been observed that these transporters are dumped into the urine after renal insult, becoming potential diagnostic tools of obstructive renal pathologies.…”

“…16,17 Previous studies showed that ureteral obstructions are associated with the decrease in renal expression of several organic anion transporters. 16,17 Moreover, it has been observed that these transporters are dumped into the urine after renal insult, becoming potential diagnostic tools of obstructive renal pathologies. 17 Based on the previously mentioned, the aim of this work was to evaluate the liver and renal expression of Oatp1 in rats with bilateral ureteral obstruction (BUO) of different time evolution.…”

“…16,17 Moreover, it has been observed that these transporters are dumped into the urine after renal insult, becoming potential diagnostic tools of obstructive renal pathologies. 17 Based on the previously mentioned, the aim of this work was to evaluate the liver and renal expression of Oatp1 in rats with bilateral ureteral obstruction (BUO) of different time evolution. In addition, the urinary excretion of Oatp1 (Oatp1 u ) was also evaluated as a potential non-invasive biomarker of obstructive nephropathy, by comparing it with classical and other more recent described parameters of renal damage.…”