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Antihypertensive therapy and progression of chronic kidney disease: Experimental studies

George L Bakris, MD
Section Editor
Gary C Curhan, MD, ScD
Deputy Editor
John P Forman, MD, MSc


Extensive studies in animals and humans have shown that progression of a variety of chronic renal diseases may be largely due to secondary hemodynamic and metabolic factors, rather than the activity of the underlying disorder. Identification of these factors, such as intraglomerular hypertension and glomerular hypertrophy, is important clinically because they can be treated, possibly preventing or minimizing further glomerular injury [1-3]. A review of the mechanisms by which these alterations might occur and how they might induce glomerular injury is available elsewhere. (See "Secondary factors and progression of chronic kidney disease".)

An important component of this approach is antihypertensive therapy, particularly with angiotensin-converting enzyme (ACE) inhibitors. The experimental studies supporting this approach will be reviewed here. The clinical trials and recommendations are presented separately. (See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults".)


From a therapeutic viewpoint, lowering the systemic blood pressure is beneficial in a variety of experimental renal diseases, at least in part by reducing the intraglomerular pressure [1,2,4-6]. Angiotensin-converting enzyme (ACE) inhibitors appear to be particularly effective in this regard; this effect may be related to reversal of the angiotensin II-induced increase in resistance at the efferent or postglomerular arteriole [4,5]. Dilatation of the efferent arteriole will facilitate blood movement out of the glomerulus, lowering the intraglomerular pressure independent of any change in systemic blood pressure. A brief review of the actions of angiotensin II on glomerular hemodynamics is available elsewhere. (See "Renal effects of ACE inhibitors in hypertension".)

It is presumed that the deleterious effect of angiotensin II represents local generation since circulating levels are normal or reduced (due to volume expansion) in many patients with chronic renal disease [7]. In the remnant kidney model of chronic renal failure, for example, endothelial injury or activation is associated with enhanced expression of angiotensinogen mRNA, which may then lead to increases in angiotensinogen and angiotensin II production [8].

Angiotensin receptor blockers — Data in animal models concerning the efficacy of angiotensin II receptor antagonists in protecting against progressive renal failure are conflicting [9]. Some studies have found that angiotensin II receptor antagonists are as effective as ACE inhibitors [10-14]. (See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults".)

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Literature review current through: Nov 2017. | This topic last updated: Nov 08, 2017.
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