Cell volume regulatory mechanisms in progression of renal disease

One of the striking morphological features of renal failure is an increase of cell volume. This review explores the role of cell volume regulatory mec hanisms in the pathophysiology of progressive renal disease. The case is ma de that TGF-beta, a major cytokine involved in the development of progressi ve renal failure, upregulates the transcription of the serum and glucocorti coid-dependent kinase hSGK1,involved in cell volume regulation. Excessive e xtracellular glucose concentrations stimulate TGF-beta1 expression and thus similarly enhance hSGK1-transcription. The kinase stimulates two mechanism s important for cell volume regulation, i.e. the renal epithelial Na+ chann el ENaC and the thick ascending limb Na+,K+,2Cl(-) cotransporter BSC1. On t he one hand, stimulation of renal tubular transport leads to renal retentio n of Na+, which favours the development of hypertension. On the other, the increase of cell volume stimulates protein synthesis and inhibits protein d egradation, contributing to the enhanced net formation and deposition of ma trix proteins. At later stages, the increase of cell volume may be reversed to atrophy, and cell death may lead to loss of functional tissue. In concl usion, progressive renal disease is paralleled by deranged cell volume regu latory mechanisms.