Published Online
on September 27, 2004

A more recent version of this article appeared on November 1, 2004

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Submitted on August 5, 2004
Revised on August 11, 2004

Pathophysiology of Hypertensive Renal Damage. Implications for Therapy

Anil K. Bidani^* and Karen A. Griffin

From Loyola University Medical Center and Edward Hines Jr. VA Hospital, Maywood, Ill.

^* To whom correspondence should be addressed. E-mail: abidani{at}lumc.edu.

Abstract--Unlike the majority of patients with uncomplicated hypertension in whom minimal renal damage develops in the absence of severe blood pressure (BP) elevations, patients with diabetic and nondiabetic chronic kidney disease (CKD) exhibit an increased vulnerability to even moderate BP elevations. Investigations in experimental animal models have revealed that this enhanced susceptibility is a consequence of an impairment of the renal autoregulatory mechanisms that normally attenuate the transmission of elevated systemic pressures to the glomeruli in uncomplicated hypertension. The markedly lower BP threshold for renal damage and the steeper slope of relationship between BP and renal damage in such states necessitates that BP be lowered into the normotensive range to prevent progressive renal damage. When BP is accurately measured using radiotelemetry in animal models, the renal protection provided by renin-angiotensin system (RAS) blockade is proportional to the BP reduction with little evidence of BP-independent protection. A critical evaluation of the clinical data also suggests that the BP-independent renoprotection by RAS blockade has been overemphasized and that achieving lower BP targets is more important than the selection of antihypertensive regimens. However, achievement of such BP goals is difficult in CKD patients without aggressive diuresis, because of their proclivity for salt retention. The effectiveness of RAS blockers in lowering BP in patients who have been adequately treated with diuretics, along with their potassium-sparing and magnesium-sparing effects, provides a more compelling rationale for the use of RAS blockade in the treatment of CKD patients than any putative BP-independent renoprotective superiority.

Key words: nephrosclerosis • autoregulation • telemetry • antihypertensive agents • renin-angiotensin system • glomerulosclerosis

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