Re: Serum creatinine elevation after renin-angiotensin system blockade and long term cardiorenal risks: cohort study
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are generally well tolerated and are used extensively in the treatment of hypertension and heart failure and in patients with renal disease for the reduction of proteinuria. A common clinical problem arises when these renin-angiotensin system–blocking drugs are started and the serum creatinine becomes elevated above the patient’s baseline level.1 This may cause concern and may lead to stopping the ACE inhibitor or ARB.
ACE inhibitors prevent the conversion of angiotensin I to angiotensin II by inhibiting the ACE inhibitor enzyme complex, while ARBs inhibit the binding of angiotensin to its AT1 receptor. Angiotensin II constricts both the afferent and efferent arterioles, but it preferentially increases efferent arteriole resistance. When an ACE inhibitor or ARB is used, there is a decrease in resistance at the efferent (post glomerular) arteriole; this lowers intra glomerular pressure and reduces the glomerular filtration rate (GFR).2
In patients with chronic kidney disease (CKD) and heart failure, the GFR is often even more dependent on an angiotensin II–induced increases in resistance at the efferent arteriole. Patients with heart failure and CKD and patients who are volume-depleted often due to over enthusiastic diuresis may be more susceptible to these hemodynamic effects. Both the serum creatinine and potassium levels should be checked from 3 days to a 1 week after an ACE inhibitor is started, particularly in patients who might be considered susceptible to the hemodynamic effects of an ACE inhibitor or an ARB.3 The rise in serum creatinine values usually begins a few days after beginning therapy with an ACE inhibitor or an ARB, as angiotensin II levels are rapidly reduced or blocked from binding.
This results in efferent arteriolar dilatation and decreased effective GFR. In a minority of cases in our experience, substantial increases in creatinine values may be from bilateral renal artery stenosis. Like blood pressure, the biochemical changes induced with medication may be substantial while patients remain clinically asymptomatic.4
1. Materson BJ, Preston RA. Chronic renal diseases: Reno protective benefits of renin-angiotensin system inhibition. Arch Intern Med. 1994;154(5):513–523.
2. The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med. 1987;316(23):1429–1435.
3. Remuzzi G, Ruggenenti P, Perico N. Chronic renal diseases: Reno protective benefits of renin-angiotensin system inhibition. Ann Intern Med. 2002;136(8):604–615.
4. Rose BD, Post TW. Clinical Physiology of Acid–Base and Electrolyte Disorders. 5th ed. New York: McGraw-Hill; 2001
Competing interests: No competing interests