Renal damage associated with proteinuria.

Experimental studies have demonstrated that proteins filtered by the glomerulus induce a proliferation of proximal tubular cells accompanied by an increased synthesis of many vasoactive and proinflammatory substances. The appearance of interstitial cellular infiltrates, a well-known finding in proteinuric diseases, precedes progressive tubulointerstitial fibrosis. Activation of the transcription factor kappaB (NF-kappaB) plays a pivotal role in the renal damage induced by proteinuria. In this scenario, any therapeutic intervention that reduces proteinuria should be beneficial for the kidney. Drugs that block the renin-angiotensin system [angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists (ARA)] have repeatedly shown striking antiproteinuric and renoprotective properties, both in experimental and clinical studies. Studies in patients with type 1 and type 2 diabetic nephropathy as well as in non-diabetic nephropathies have confirmed that the renoprotection obtained with ACEI/ARA is closely related with their antiproteinuric effect and is largely independent of blood pressure changes. However, resistance to the antiproteinuric effect of ACEI/ARA is a common clinical observation. Several therapeutic measures (that is, adequate blood pressure control, early introduction of ACEI/ARA, dietary protein restriction, low salt diets, weight loss in overweight patients, addition of a diuretic, increasing ACEI/ARA dose titrated against proteinuria levels, combined therapy ACEI plus ARA, addition of drugs with antiproteinuric effect such as non-dihydropiridine calcium channel blockers or NSAIDs) may increase the proteinuria reduction induced by ACEI and ARA.