Nephroprotection by Antihypertensive Agents

Abstract

Arterial hypertension is one of the few factors confirmed to accelerate the development of renal failure. Conversely, several studies have documented that systematic reduction of the blood pressure slows the progression of renal failure. It is postulated that 24-h reduction of the blood pressure should be achieved, best controlled by ambulatory blood pressure monitoring, and that the elevated blood pressure should be reduced to at least below 140/90 mm Hg. In assessing the progression of renal failure, the renal plasma flow and the glomerular filtration rate are measured, because both renal hemodynamic parameters correlate with the degree of severity of histologic changes. Renal blood flow is increased by angiotensin-converting enzyme (ACE) inhibitors, and unchanged or slightly increased by calcium antagonists, whereas renal plasma flow is somewhat decreased by diuretics and beta-blockers. A further criterion for assessing the potential nephroprotective properties of antihypertensive agents is their influence on intraglomerular hemodynamics. According to animal studies, ACE inhibitors can prevent elevated intraglomerular pressure and the associated development of glomerulosclerosis. Retrospective and prospective studies could also demonstrate these findings in human subjects. Despite an equally effective reduction of systemic blood pressure by the antihypertensive medication, there was a lesser reduction in glomerular filtration rate with ACE inhibitors than when another conventional antihypertensive medication was used. It should be further clarified whether these favorable effects of ACE inhibitors were due also to antiproliferative properties (e.g., blockade of the growth-stimulating factor angiotensin II). The results for calcium antagonists are contradictory. Their protective properties in acute renal failure have been documented, but there are no clinical studies verifying the effect of long-term administration of calcium antagonists on the development of renal failure. To summarize, it has been confirmed to date that systemic antihypertensive therapy slows the progression of renal failure of any etiology, and there is initial proof that ACE inhibitors are superior to other antihypertensive agents in this respect.