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Cyclooxygenase inhibition causes marked impairment of renal function in elderly subjects treated with diuretics and ACE-inhibitors
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy. (Hammarlund-Udenaes)
2005 (English)In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 7, no 6, 1049-1056 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2005. Vol. 7, no 6, 1049-1056 p.
Keyword [en]
ACE-inhibitors, NSAIDs, heart failure, renal function, glomerular filtration rate
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-104670DOI: 10.1016/j.ejheart.2004.10.005ISI: 000234381000016PubMedID: 16227143OAI: oai:DiVA.org:uu-104670DiVA: diva2:220052
Available from: 2009-05-29 Created: 2009-05-29 Last updated: 2010-10-25Bibliographically approved

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