Nondiabetic kidney disease

Abstract

The burden of chronic kidney disease represents a major health problem. Experimental studies and evidence in humans suggest that renal damage progresses independently of the initial cause and follows pathogenic mechanisms that are common among different nephropathies. After an initial renal injury, the number of functioning nephrons declines and remaining ones undergo hypertrophy, with concomitant lowering of arteriolar resistance and increased glomerular plasma flow. This compensatory mechanism allows preservation of glomerular filtration rate but is ultimately detrimental. Indeed, high intraglomerular capillary pressure impairs the size selectivity of the membrane and allows passage of larger molecules, such as proteins. An excess of proteins in the tubular lumen exerts a nephritogenic effect that fuels progressive renal function loss. In animals with proteinuric renal disease, glomerular hypertension and sieving dysfunction are ameliorated by drugs that inhibit the activity of the renin-angiotensin system (RAS), such as angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. RAS inhibitor therapy is the key component of intervention strategies aimed at retarding or preventing progression of chronic renal disease, and available data indicate that effective inhibition of the RAS may even regress established renal injury in experimental animals and improve kidney function in patients otherwise expected to relentlessly progress to end-stage renal disease. © 2010 Springer-Verlag Milan.