Renal effects of angiotensin-converting enzyme inhibition in cardiac failure

Compensatory mechanisms such as systemic vasoconstriction and sodium retention are activated to various degrees in patients with congestive heart failure (CHF). The renin-angiotensin system (RAS) mediates many of these compensatory responses. Increased angiotensin can result in net vasoconstriction and increase afterload. In addition, it contributes to the avid sodium retention that occurs in patients with CHF. The RAS promotes sodium retention by enhancing proximal tubular reabsorption of sodium and water through changes in intrarenal hemodynamics. In addition, the direct renal tubular influence of angiotensin II and aldosterone contribute to sodium retention. In experimental heart failure in the rat, angiotensin activation leads to reduction in effective plasma flow whereas the glomerular filtration rate was unchanged. In clinical CHF, activation of the RAS may also contribute to azotemia in patients with CHF. Significant correlations between serum creatinine levels and plasma renin activity have been observed. Furthermore, renal plasma flow and the glomerular filtration rate frequently improve after therapy with converting-enzyme inhibitors (CEIs). Occasionally, however, CEIs may produce an excessive fall in systemic BP and, hence, renal perfusion pressure, which may overcome autoregulatory mechanisms and contribute to a deterioration in renal function. CEIs enhance the effectiveness of furosemide in promoting natriuresis and correction of hyponatremia. Diuretic-induced hypokalemia can also be corrected by angiotensin-converting enzyme (ACE) inhibitors due to blockade of aldosterone production. On the basis of these results, we recommend titration of the ACE inhibitors' dose to minimize hypotension and the concurrent use of furosemide in patients with CHF receiving ACE inhibitors, especially for those in whom azotemia, hyponatremia, and hypokalemia complicate the course.