Selective cyclooxygenase-2 (COX-2) inhibition reduces proteinuria in renal patients

Abstract

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. 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. 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. 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.