Renal expression and urinary excretion of Na+/dicarboxylate cotransporter 1 (NaDC1) in obstructive nephropathy: a candidate biomarker for this pathology

Abstract

Obstructive nephropathy is characterized by alterations in renal function that depends on the degree and type of obstruction. To increase the knowledge about the physiopathological mechanisms involved in the renal damage associated with bilateral ureteral obstruction (BUO), we studied the renal expression and function (as urinary citrate excretion) of sodium-dependent dicarboxylate cotransporter (NaDC1) in rats. In addition, we evaluated the urinary excretion of NaDC1 as a candidate biomarker for this pathology. Male Wistar rats underwent bilateral ureteral obstruction for 1 (BUO1), 2 (BUO2), 5 (BUO5), and 24 (BUO24) h or sham operation. After 24 h of ureteral releasing, traditional parameters of renal function and citrate levels were determined, and NaDC1 levels were evaluated in total renal homogenates, apical plasma membranes, and urine by electrophoresis and Western blotting. Traditional parameters of renal function were only modified in BUO5 and BUO24. The renal expression of NaDC1 was decreased in BUO5 and BUO24, with a concomitant increase in urinary excretion of citrate. Moreover, the urinary excretion of NaDC1 increased after short times of ureteral obstruction (BUO1 and BUO2) and was positively correlated with the time elapsed after obstruction. The results obtained from the renal expression of NaDC1 could explain an adaptive mechanism to prevent the formation of kidney stones by increasing the levels of citrate, a calcium chelator. The urinary excretion of NaDC1 could be postulated as an early biomarker of obstructive nephropathy that also gives information about the duration of the obstruction.

Time evolution of methotrexate‐induced kidney injury: A comparative study between different biomarkers of renal damage in rats

“…Each value represents mean ± standard error from experiments carried out in triplicate on four different tissue‐derived samples or urine‐derived samples for each experimental group. The protein abundances of Oat5 and NGAL in the urine samples were expressed as optical density (O.D., arbitrary units) related to urinary creatinine concentration ([O.D./10 μL]/Cr U ) in order to correct for variations in urine production as previously reported …”

“…For densitometry of immunoblots, samples from treated rats were in order to correct for variations in urine production as previously reported. 10,11,14,46,49…”

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

“…Several experimental models have been used as insight into the pathophysiology of postrenal injury. The surgical procedure of complete obstruction of both ureters has been used in our laboratory and also by other authors 19,21,22 . Campagno et al 21 have recently demonstrated modifications in renal haemodynamic and in some tubular function parameters, as well as in the renal architecture after 5 and 24 hours of bilateral ureteral obstruction.…”

“…The surgical procedure of complete obstruction of both ureters has been used in our laboratory and also by other authors 19,21,22 . Campagno et al 21 have recently demonstrated modifications in renal haemodynamic and in some tubular function parameters, as well as in the renal architecture after 5 and 24 hours of bilateral ureteral obstruction. These experimental groups showed interstitial fibrosis, cell desquamation and tubular dilatation, both in proximal tubules and in more distal segments.…”

Solute Carrier Transporters as Potential Targets for the Treatment of Metabolic Disease

“…In rats, Slc13a2 expression was increased on renal proximal tubule epithelial cells in a model of chemically-induced nephrolithiasis (He et al, 2004b). Nevertheless, renal NaDC1 expression was reduced in a rat model of obstructive nephropathy, which can be caused by nephrolithiasis (Campagno et al, 2018). Finally, the opposing regulation of Slc13a2 in different animal models needs further evaluation.…”