Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine - Is this a cause for concern?

Background: Reducing the actions of the renin-angiotensin-aldosterone syste m with angiotensin-converting enzyme inhibitors (ACEIs) slows nephropathy p rogression in patients with or without diabetes. Post hoc analyses of many ACEI-based clinical trials demonstrate the greatest slowing of renal diseas e progression in patients with the greatest degree of renal insufficiency a t study initiation. However, many physicians fail to use ACEIs or angiotens in receptor blockers in patients with renal insufficiency for fear that eit her serum creatinine or potassium levels will rise. Objective: To determine if limited initial reduction in either glomerular f iltration rate (GFR) or elevation in serum creatinine levels, associated wi th ACEI or angiotensin receptor blocker use, results in long-term protectio n against decline in renal function in patients with renal insufficiency. Methods: We reviewed 12 randomized clinical trials that evaluated renal dis ease progression among patients with preexisting renal insufficiency. Six o f these studies were multicenter, double-blinded, and placebo controlled, w ith the remainder being smaller randomized studies with a minimum 2-year fo llow-up on renal function. These investigations evaluated patients with and without diabetes or systolic heart failure. Average duration of follow-up for all studies was 3 years. Trials were examined in the context of changes in either serum creatinine levels or GFR in the group randomized to an ACE I (N = 1102). Sixty-four percent of these individuals (705/ 1102) had renal function data at both less than 6 months and at the end of the study. Results: Most trials demonstrated that patients with preexisting renal insu fficiency manifested an acute fall in GFR, a rise in serum creatinine, or b oth. Those randomized to an ACEI with a serum creatinine level of 124 mu mo l/L or greater (greater than or equal to 1.4 mg/dL) demonstrated a 55% to 7 5% risk reduction in renal disease progression compared with those with nor mal renal function randomized to an ACEI. An inverse correlation was observ ed between the amount of renal function loss at baseline and the subsequent rate of annual decline in renal function following randomization to an ant ihypertensive regimen that contained an ACEI. Conclusions: A strong association exists between acute increases in serum c reatinine of up to 30% that stabilize within the first 2 months of ACEI the rapy and long-term preservation of renal function. This relationship holds for persons with creatinine values of greater than 124 mu mol/L (>1.4 mg/dL ). Thus, withdrawal of an ACEI in such patients should occur only when the rise in creatinine exceeds 30% above baseline within the first 2 months of ACEI initiation, or hyperkalemia develops, ie, serum potassium level of 5.6 mmol/L or greater.