Effects of sulindac on renal function and prostaglandin synthesis in patients with moderate chronic renal insufficiency.
The renal effects of therapeutic doses of sulindac were studied in nine patients with stable renal insufficiency, mean creatinine clearance 37.0 +/- 2.2 ml min-1 1.73 m-2 (range 24.7-54.6 ml min-1 1.73 m-2). Nine days' treatment with sulindac produced a small, but significant, reduction in the mean creatinine clearance (37.0 +/- 2.2 to 34.7 +/- 2.2 ml min-1 1.73 m-2; P less than 0.02) and 99mTc diethylenetriaminepenta-acetate (DTPA) clearance (35.5 +/- 3.4 to 31.4 +/- 3.6 ml min-1 1.73 m-2; P less than 0.02) without altering body weight, effective renal plasma flow [131I]hippuran clearance), plasma renin activity (PRA), 24 h urinary volume or electrolyte excretion. After discontinuation of sulindac, creatinine clearance returned to pretreatment values. In five female patients, pretreatment urinary excretion of the 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), a stable breakdown product of prostacyclin (PGI2), was significantly reduced (P less than 0.02) when compared with four healthy controls, whereas prostaglandin E2 (PGE2) was unchanged. Administration of sulindac did not significantly alter the excretion rate of PGE2 or 6-ketoPGF1 alpha in this group of patients. In chronic renal disease with moderate renal impairment, reduced renal prostacyclin synthesis may be an important predisposing factor to the renal toxicity associated with the use of non-steroidal anti-inflammatory drugs (NSAID). Short term use of sulindac in therapeutic doses does not appear to influence the excretion of prostaglandins and produces only a minor reversible change in renal function; used cautiously it may have advantages over other NSAID in these patients.
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000328:Adult; D003404:Creatinine / Q000652:urine; D015232:Dinoprostone; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007192:Indenes / Q000627:therapeutic use*; D007668:Kidney / Q000098:blood supply / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D011453:Prostaglandins / Q000652:urine*; D011458:Prostaglandins E / Q000652:urine; D012083:Renin / Q000097:blood; D013467:Sulindac / Q000627:therapeutic use*
D007192:Indenes; D011453:Prostaglandins; D011458:Prostaglandins E; D013467:Sulindac; D015121:6-Ketoprostaglandin F1 alpha; D003404:Creatinine; D012083:Renin; D015232:Dinoprostone