Aldose reductase in the etiology of diabetic complications: 2. Nephropathy

The progression of diabetic nephropathy can be arrested by an improvement in diabetic control. High glucose concentrations increase the flux through the aldose reductase pathway, and it has been proposed that this may contribute to renal damage. Aldose reductase is present in both the glomerulus and the renal tubule. Biochemical changes associated with increased sorbitol production have been demonstrated in animal models, including myo-inositol depletion, reduced Na+-K+ ATPase activity, and activation of the pentose phosphate and glucuronate-xylose pathways. Selective inhibition of aldose reductase reverses these biochemical changes and prevents some of the structural and functional abnormalities in diabetic rats. The potential beneficial effects of aldose reductase inhibitors on diabetic kidney disease in man are at present being investigated.