Effects of sulindac and ibuprofen in patients with chronic glomerular disease. Evidence for the dependence of renal function on prostacyclin.
We investigated whether the glomerular synthesis of prostacyclin modulates the renal blood flow and glomerular filtration rate in chronic glomerular disease. The urinary excretion of 6-keto-prostaglandin F1 alpha, a stable breakdown product of prostacyclin, was significantly (P less than 0.01) reduced in 20 women with chronic glomerular disease, as compared with 19 controls, whereas excretion of urinary prostaglandin E2 was unchanged. In 10 patients randomly assigned to one week of treatment with ibuprofen, excretion of urinary 6-keto-prostaglandin F1 alpha and prostaglandin E2 was reduced by 80 per cent, the level of serum creatinine was increased by 40 per cent, and creatinine and para-aminohippurate clearances were reduced by 28 and 35 per cent, respectively. The reduction of both clearances was inversely related (P less than 0.01) to the basal urinary excretion of 6-keto-prostaglandin F1 alpha but not of prostaglandin E2. No functional changes were detected in five healthy women, despite a similar suppression of renal prostacyclin synthesis by ibuprofen. In contrast, one week of treatment with sulindac did not affect renal prostacyclin synthesis or renal function in the other 10 patients, despite a marked inhibition of extrarenal cyclooxygenase activity. We conclude that in patients with mild impairment of renal function, the renal blood flow and glomerular filtration rate are critically dependent on prostacyclin production. In such patients sulindac may be a safe substitute for other nonsteroidal antiinflammatory drugs.
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D003404:Creatinine / Q000378:metabolism; D015232:Dinoprostone; D011464:Epoprostenol / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology* / Q000627:therapeutic use; D007192:Indenes / Q000494:pharmacology*; D007668:Kidney / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000378:metabolism; D008875:Middle Aged; D011458:Prostaglandins E / Q000652:urine; D012079:Renal Circulation; D013467:Sulindac / Q000494:pharmacology* / Q000627:therapeutic use; D010130:p-Aminohippuric Acid / Q000097:blood
D007192:Indenes; D011458:Prostaglandins E; D013467:Sulindac; D015121:6-Ketoprostaglandin F1 alpha; D003404:Creatinine; D011464:Epoprostenol; D015232:Dinoprostone; D007052:Ibuprofen; D010130:p-Aminohippuric Acid