Complementary effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in slowing the progression of chronic kidney disease
Section snippets
RAAS and CKD
The RAAS is a critical link in the pathologic relationship between hypertension and renal disease. Regulation of extracellular fluid volume, sodium and water homeostasis, and electrolyte balance are primary functions of the RAAS. The sympathetic nervous system and vasoactive hormones (eg, endothelin, nitric oxide [NO], adenosine, and atrial natriuretic peptide) work with the RAAS to coordinate its hemodynamic effects and thereby maintain blood pressure (BP).
The cascade of peptide hormones that
Progression of renal dysfunction
There are many causes of renal dysfunction, including genetic abnormalities, autoimmune disease, toxic exposures, infections, and trauma, but hypertension and diabetes are among the most common causes.12 Because the primary function of the kidney is to filter the blood, thereby, regulating blood volume and pressure and eliminating unwanted molecules while retaining essential ones, deterioration in renal function is reflected in the increasing inability of the kidney to filter the blood
Pharmacologic blockade of the RAAS
As has been detailed elsewhere in this supplement, ACEIs block the conversion of AI to AII, the peptide thought to initiate most of the deleterious effects of the RAAS. Because ACEIs also metabolize bradykinin, a direct vasodilator, and promote release of the vasodilators NO and prostacyclin, a second effect of ACEIs is the reduction of bradykinin degradation.32 However, studies have shown that levels of circulating AII return to pretreatment levels in patients receiving long-term ACEI therapy.
Guidelines
The National Kidney Foundation Kidney Disease Outcomes Quality Initiative has prepared guidelines for the use of antihypertensive therapy, specifically for patients with diabetic kidney disease (with or without hypertension) or those with nondiabetic kidney disease with proteinuria.4 The recommended target BP for patients with diabetes is currently 130/80 mm Hg. In both situations, the guidelines call for initiation of therapy with either an ACEI or ARB. They further state that, at this time,
Summary
Key points when considering dual therapy are shown in Table I. Disruption of the RAS system, thereby, blocking the pathogenic effects of AII, is effective in slowing the onset and progression of CKD. Use of ACEIs and ARBs individually has been shown to decrease BP, reduce proteinuria, and slow progression of CKD. Therefore, the combination of an ACEI and ARB not only would block ACE-catalyzed production of AII and decrease metabolism of bradykinin but also antagonize the negative effects of AII
Disclosures
Editorial assistance was provided by Publication CONNEXION. This work was supported by Boehringer Ingelheim Pharmaceuticals Inc (Ingelheim, Germany).
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