[Molecular mechanism of proteinuria caused progression of chronic renal disease]

Increasing numbers of clinical and experimental studies have proved that proteinuria plays a key role in the progression of chronic renal disease. In recent years, some molecular mechanisms of how proteinuria causes further kidney injuries have been revealed by many researches, although there are still many questions to be answered. Proteinuria triggers chemokine expression of tubular epithelial cells and activates complements, which result in interstitial inflammation and fibrosis; proteinuria also induces the apoptosis of tubular epithelial cells. Albumin in urine is considered as the main culprit, but other elements in proteinuria have also been suspected to cause renal damage, too. On the other hand, serum proteins leaking from glomerular barrier also adversely affect podocytes. Ultrafiltered serum proteins induce morphological changes and functional impairment of podocytes, resulting in exacerbating proteinuria; furthermore, TGF-ß1 up-regulated by podocytes in response to protein overload contributes to the sclerosis of glomeruli. Studies on the mechanism of how proteinuria accelerates kidney diseases are important because they may offer novel therapeutic targets for controlling chronic kidney disease. For example, targeting directly on the complement synthesis and activation in proximal tubules, or chemokine production in tubular cells might be beneficial for preventing the progression of chronic proteinuric kidney disease to end stage renal disease.