Regulation of renal proximal and distal tubule transport: Sodium, chloride and organic anions

Renal tubular transport and its regulation are reviewed for Na⁺ (and Cl^-), and for fluid and organic anions (including urate). Filtered Na⁺ (and Cl^-) is reabsorbed along the tubules but only in mammals and birds does most reabsorption occur in the proximal tubules. Reabsorption involves active transport of Na⁺ and passive reabsorption of Cl^-. The active Na⁺ step always involves Na-K-ATPase at the basolateral membrane, but the entry step at luminal membrane varies among tubule segments and among vertebrate classes (except for Na ⁺-2Cl^--K⁺ cotransporter in diluting segment). Regulation can involve intrinsic, neural and endocrine factors. Proximal tubule fluid reabsorption is dependent on Na⁺ reabsorption in all vertebrates studied, except ophidian reptiles. Fluid secretion occurs in glomerular and aglomerular fishes, reptiles and even mammals, but its significance is not always clear. A non-specific transport system for net secretion of organic anions (OAs) exists in the proximal renal tubules of almost all vertebrates. Net transepithelial secretion involves: (1) transport into the cells at the basolateral side against an electrochemical gradient by a tertiary active transport process, in which the final step involves OA/α-ketoglutarate exchange and (2) movement out of the cells across the luminal membrane down an electrochemical gradient by unknown carrier-mediated process(es). Regulation may involve protein kinase C and mitogen-activated protein kinase. Urate is net secreted in the proximal tubules of birds and reptiles. This process is urate-specific in reptiles but in birds, it may involve both a urate-specific system and the general OA system.