© 2005 European Society of Cardiology
Cyclooxygenase inhibition causes marked impairment of renal function in elderly subjects treated with diuretics and ACE-inhibitors
a Department of Cardiology, Malmö University Hospital Malmö, Sweden
b Hospital Pharmacy, Malmö University Hospital Malmö, Sweden
c Department of Clinical Pharmacology, Lund University Hospital S-221 85 Lund, Sweden
* Corresponding author. Tel.: +46 46 177979; fax: +46 46 176085. E-mail address: Peter.Hoglund{at}skane.se
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Abstract |
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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 quantify 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 bendroflumethiazide 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/min. After pre-treatment, diclofenac further reduced GFR from 60 (52–67) to 48 (40–55) ml/min. After diclofenac 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.
Key Words: ACE-inhibitors • NSAIDs • Heart failure • Renal function • Glomerular filtration rate
Received April 28, 2004; Revised July 12, 2004; Accepted October 14, 2004
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