Angiotensin converting enzyme inhibitors and progressive renal insufficiency. Current experience and future directions.

STUDY OBJECTIVE To review the rationale for using angiotensin converting enzyme (ACE) inhibitors in progressive renal disease, and to evaluate the experience with these agents in patients with hypertension and renal insufficiency. DATA IDENTIFICATION Experimental and clinical studies published from January 1977 to November 1988 were identified by searching the literature and by extensive hand searching of bibliographies of identified articles. STUDY SELECTION Experimental studies of glomerular function during therapy with ACE inhibitors or other antihypertensive regimens were reviewed. Series using ACE inhibitors for treating hypertensive patients with renal disease were evaluated and reports of adverse events were studied. RESULTS OF DATA SYNTHESIS Experimentally, ACE inhibitors seem to decrease glomerular injury by reducing both systemic and glomerular hypertension. Clinically, ACE inhibitors reduce systemic blood pressure in hypertensive patients with diabetic and nondiabetic renal disease without causing dramatic changes in glomerular filtration rate or renal blood flow. Most studies of nondiabetic renal insufficiency suggest that proteinuria is reduced in most patients. However, no long-term controlled study on the effect of ACE inhibitors on the progression rate of nondiabetic renal disease has been completed. ACE inhibitors have not yet been approved by the Food and Drug Administration (FDA) for treating or preventing progressive renal disease. Such use would therefore be considered "innovative" therapy. CONCLUSIONS ACE inhibitors are tolerated by azotemic patients, although transient reductions in renal function can occur. Patients with bilateral renal insufficiency or low cardiac output are at increased risk for developing reversible acute renal insufficiency. Hyperkalemia may occur, particularly in patients with diabetes or severe renal insufficiency. In many patients with renal disease, ACE inhibitors dramatically reduce proteinuria, but whether they also reduce the rate of progression of renal disease remains unproved.