In-Depth Review Progression of Renal Disease: Renoprotective Specificity of Renin-Angiotensin System Blockade

Abstract

Recent guidelines for management of patients with chronic kidney disease recommend both lower optimal BP targets and agents that block the renin-angiotensin system (RAS) for specific additional BP-independent renoprotection. Although there are other compelling rationales to use RAS blockade in patients with chronic kidney disease, including its antihypertensive effectiveness and ability to counteract the adverse effects of diuretics, a critical review of the available scientific evidence suggests that the specificity of renoprotection that is provided by RAS blockade has been greatly overemphasized. Little evidence of truly BP-independent renoprotection is observed in experimental animal models when ambient BP is assessed adequately by chronic continuous BP radiotelemetry. Although the clinical trial evidence is somewhat stronger, nevertheless, even when interpreted favorably, the absolute magnitude of the BP-independent component of the renoprotection that is observed with RAS blockade is much smaller than what is due to its antihypertensive effects. Clin J Am Soc Nephrol 1: 1054–1065, 2006. doi: 10.2215/CJN.02231205 T he recognition that chronic kidney disease (CKD), re-gardless of cause, tends to progress to ESRD has led toextensive investigations of the underlying mechanisms and of therapeutic strategies to combat such progression. Al-though controversy persists about the relative pathogenetic importance of the individual mechanisms (vide infra), a general consensus has emerged regarding the therapeutic approach t