Cyclooxygenase inhibition causes marked impairment of renal function in elderly subjects treated with diuretics and ACE-inhibitors

Background: Treatment with angiotensin-converting enzyme (ACE)-inhibitors is known to cause an initial reduction in glomerular filtration rate (GFR) in patients with congestive heart failure. The long-term beneficial effects of ACE-inhibitors in these patients can be counteracted by cyclooxygenase-inhibitors. Aims: To quantity the negative renal effects of the cyclooxygenase-inhibitor diclofenac in elderly healthy subjects and to assess how treatment with an ACE-inhibitor, after activation of the renin-angiotensin system, influences these renal effects. Methods: Fourteen elderly, healthy subjects received oral diclofenac and placebo in a double-blind cross-over fashion. The study was divided in two parts; in part one, subjects received no pre-treatment and in part two, the Subjects were given pre-treatment with bendroflurnethiazide and enalapril in order to activate the renin-angiotensin system. Results: Diclofenac induced significant (p < 0.05) decreases in GFR, urine flow, excretion rates of sodium and potassium, electrolyte clearance, osmolality clearance and free water clearance both with and Without renin-angiotensin system activation. Least square means (95% CI) of all observations during the first 6 h after dosing showed that diclofenac caused a reduction in GFR from 71 (64-78) to 59 (52-66) ml/mm. After pre-treatment, diclofenac further reduced GFR from 60 (52-67) to 48 (40-55) ml/min. After dicloflenac administration, urine flow fell from 7.4 (6.4-8.3) to 5.1 (4.2-6.1) ml/min, after pre-treatment, diclofenac gave a further reduction from 4.1 (3.1-5.1) to 2.2 (1.3-3.2) ml/min. More than half of the reductions were caused by the pre-treatment. Conclusion: Renal function in elderly, healthy Subjects is impaired after acute intake of diclofenac. This impairment is observed both with and without activation of the renin-angiotensin system and ACE-inhibitor treatment but is more pronounced after pre-treatment. (c) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.