NDT Advance Access published online on November 26, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn644
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Selective cyclooxygenase-2 (COX-2) inhibition reduces proteinuria in renal patients
1 Division of Nephrology, Department of Internal Medicine, Groningen University Medical Centre, University of Groningen 2 Department of Internal Medicine, Twenteborg Hospital, Almelo 3 Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam 4 Department of Clinical Pharmacology, Groningen University Medical Center, University of Groningen, The Netherlands
Correspondence and offprint requests to: Liffert Vogt, Department of Internal Medicine, room F4-222, Academic Medical Center, University of Amsterdam, The Netherlands. Tel: +31-20-566-9111; Fax: +31-020-566-4440; E-mail: liffertvogt{at}hotmail.com
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Abstract |
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Background. Renoprotection is predicted by the antiproteinuric efficacy of a pharmacological agent. Non-steroidal anti-inflammatory drugs (NSAIDs) interfering non-selectively in the prostaglandin system have strong antiproteinuric potency without reduction of systemic blood pressure. The effect of the selective COX-2 inhibitor rofecoxib in proteinuric patients is unknown, granted recently reported detrimental effects in non-renal patients. Short-term effects of rofecoxib on proteinuria and blood pressure as compared to NSAID and RAAS blockade were studied.
Methods. Sixteen stable patients [mean proteinuria 4.4 g/ day; MAP 103 mmHg)] were included after a wash-out period. Hydrochlorothiazide 12.5 mg QD was given throughout. Additional blood pressure control was ensured by non-RAAS blocking antihypertensive agents. Patients received rofecoxib 25 mg QD, 50 mg QD and indomethacin 75 mg BID in randomized order for 4 weeks. Thereafter, a subset of the included patients (n = 11) received lisinopril 40 mg QD for 6 weeks preceded by a wash-out period.
Results. Rofecoxib exerted a dose-dependent antiproteinuric effect. As compared to rofecoxib 25 and 50 mg, indomethacin was more effective [–18, –28 versus –49% (n = 16; P < 0.05)]. As compared to rofecoxib 50 mg, lisinopril was more effective [–21 versus –51% (n = 11; P < 0.05)]. No significant blood pressure changes were observed after rofecoxib and indomethacin, whereas lisinopril had a significant antihypertensive effect.
Conclusion. Selective COX-2 inhibition reduces proteinuria without reduction of systemic blood pressure, pointing towards a specific renal effect, and may serve as a novel non-hypotensive adjunct antiproteinuric treatment.
Keywords: chronic renal failure; COX-2 inhibition; NSAID; proteinuria; RAAS blockade
Received for publication: 15. 7.08
Accepted in revised form: 24.10.08