Relationship between proteinuria and progressive renal disease.

Numerous studies have shown a correlation between the degree of proteinuria and rate of progression of renal failure. This has led to the hypothesis that proteinuria may be an independent mediator of progression, rather than simply a marker of glomerular dysfunction. The mechanisms by which the presence of proteins in tubular fluid may promote the progression of chronic renal failure are not yet determined. However, the observation that proximal tubular cells reabsorb proteins from the tubular fluid has led to the suggestion that proteins or associated molecules may adversely affect tubular cell biological state. In this regard, it is of note that tubulointerstitial disease correlates better with the level of renal function than changes in the glomerulus. Further support for this hypothesis comes from the observations that strategies that reduce proteinuria, including control of hypertension, angiotensin-converting enzyme inhibition, and low-protein diets, reduce the rate of progression of renal failure.