Prevention, protection, and the intrarenal renin-angiotensin systems.
The use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor antagonists, or aldosterone antagonists can have important beneficial effects on the progression of renal disease associated with glomerular and interstitial fibrosis, especially if the adverse side effects (eg, hyperkalemia) can be minimized. Because it appears that chronic renal insufficiency and proteinuria may well be cardiovascular risk factors, it is exciting to note that recent large scale epidemiologic studies (Heart Outcomes and Prevention Evaluation [HOPE]) have shown both cardioprotective and renoprotective effects of ACE inhibition. It appears paradoxic that such renoprotective effects are clearly evident in diabetes mellitus in which the plasma renin activity may be suppressed. Even in this setting, it appears that there is activation of the renal angiotensin system(s), and inhibitions of these intrarenal systems are involved in the renoprotective effects of these agents. Recent studies have identified nearly all of the components needed to generate angiotensin II in the renal luminal compartment, and suggest that there may be a direct effect through AT(1) receptors on NaCl transport in the distal nephron. The possibility that the components of this intraluminal renin-angiotensin system may be acutely regulated by variations in dietary salt intake provides an opportunity to better understand the normal maintenance of salt balance. Whether or not inhibition of these pathways is involved in the renoprotective effects of ACE inhibitors and angiotensin receptor antagonists is an important issue to be addressed.
Warnock
D G
DG
Division of Nephrology, Department of Medicine, Nephrology Research and Training Center, University of Alabama at Birmingham, UAB Station, Birmingham, AL 35294-0006, USA. dwarnock@nrtc.uab.edu
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D003928:Diabetic Nephropathies / Q000503:physiopathology; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy* / Q000503:physiopathology; D017257:Ramipril / Q000627:therapeutic use; D012079:Renal Circulation; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D012982:Sodium, Dietary / Q000008:administration & dosage
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D012982:Sodium, Dietary; D017257:Ramipril