Effect of rofecoxib on the glomerular filtration rate, proteinuria and the renin-angiotensin-aldosterone system in elderly subjects with chronic renal impairment

Considering the increasing popularity and prescribing of specific COX-2 inhibitors, a new class of NSAIDs lacking gastrointestinal side effects, the evaluation of their effects on renal function has become very important. Objective: The aim of the study was to evaluate the effect of rofecoxib on GFR, proteinuria and the renin-angiotensin-aldosterone system (RAAS) in elderly patients with chronic renal impairment under controlled conditions of water and salt intake. Subjects: There were ten patients (average age 67 years, range 53 - 80 years) with analgesic or vascular nephropathy (average GFR 54 ml/min/1.73 m(2), range 30 - 79 ml/min/ 1.73 m(2)) given 25 mg rofecoxib daily for seven days under balanced conditions of water and sodium metabolism (salt intake 6 - 8 g/24 hours). Methods: The effect of rofecoxib on GFR measured using inulin clearance (C-in), creatinine clearance (C-Cr) serum cystatin C concentration (S-cystatin), tubular creatinine secretion (using the ratio C-Cr/C-in), 24-hour urinary excretion of albumin (UalbV) and prostaglandins (UPGE2V and UPGF2 alpha V), basal and stimulated plasma renin activity (PRA) and serum aldosterone concentration (S-aldosterome) was evaluated before and on Day 7 during rofecoxib treatment. Results: Rofecoxib did not significantly change C-in, C-Cr, S-cystatin, CCr/Cin and UalbV. However, UPGE2V and UPGF2aV were decreased during rofecoxib administration (p = 0.059 and p = 0.024, respectively). Rofecoxib attenuated the stimulated rise of PRA and S-aldosterone (p = 0.019 and p = 0.008, respectively). Conclusions: Short-term rofecoxib administration was not associated with significant change in GFR in elderly patients with moderate chronic renal impairment under conditions of balanced salt and water metabolism despite significant attenuation of RAAS activity. Since the C-Cr/C-in ratio did not change in our study, we assume rofecoxib to have no influence on creatinine tubular secretion.