Renal response of solute carrier transporters and related proteins in obstructive jaundice

Abstract

Obstructive jaundice mainly takes place after cholelithiasis and neoplasms that affect the pancreas and the common bile duct. The liver and kidney eliminate toxins, pharmacotherapeutic drugs, and endogenous metabolites. It has been reported that the alteration of one route of excretion can be compensated by the other route. Modifications in the expression of several carrier proteins have been observed after the impairment of the hepatic function. The present work updates the modifications reported in the renal expression and in the urinary levels of some proteins belonging to the solute carrier family (such as Oatp1, Oat1, Oat3, Oat5, Asbt, and NKCC2) and some proteins related in some way to these ones (such as AQP2,Cav-1, and Cav-2). An increased renal expression of Oatp1, Oat1, Oat3, Oat5, and a decreased abundance of Abst was observed after 21 h of bile duct ligation, explaining the increase in the renal clearance of different compounds that could not be excreted by the liver because the biliary excretion is impaired. Moreover, the decreased expression of NKCC2 and AQP2 together with the increase in medullary renal blood flow could account for the increase in the urinary flow previously reported in this pathological state. In addition, a decreased expression of Cav-1 and an increased expression of Cav-2 in kidneys were reported in the early phase of acute cholestasis. It is well-known that renal function is altered during cholestasis and that the impairment of this organ increases with the time course of cholestasis. Increase urinary levels of NaDC1, Cav-1, andCav-2 together with a decrease of Oat5, plus the absence of modifications of NKCC2 and AQP2 were detected after 21 h of bile duct ligation in the absence of alterations in traditional parameters of renal function. Thus, the urinary levels of these proteins were proposed as a novel panel of biomarkers of the early phase of acute obstructive jaundice.