Proteinuria as a mediator of tubulointerstitial injury

Abstract

Proteinuria is one of the most potent risk factors for renal disease progression in patients with glomerular diseases. Studies in disease models have helped to delineate mechanisms leading to renal structural damage due to persistent dysfunction of the glomerular barrier to proteins, even when the primary immune or nonimmune insult to the kidney has ceased. The main focus of this review is the role of the tubular epithelial cell in the induction of interstitial inflammatory and fibrogenic reactions to ultrafiltered proteins. Antiproteinuric drugs (angiotensin-converting enzyme inhibitors, ACEi) while preserving the integrity of the glomerular permselective barrier limit both proteinuria and protein-dependent processes which contribute to tubulointerstitial injury, and in so doing ACEi halt the progression of proteinuric nephropathies toward terminal renal failure.