title: Effect of cyclooxygenase-2 inhibition on renal function in elderly persons receiving a low-salt diet. A randomized, controlled trial.
abstract: BACKGROUND
  Most nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both cyclooxygenase-1 (COX-1), whose inhibition is associated with gastrointestinal ulceration, and COX-2, whose inhibition is associated with therapeutic benefits. Although agents that do not produce COX-1 activity may have fewer adverse effects, targeted disruption of the COX-2 allele in mice has resulted in severe renal problems, suggesting that COX-2 inhibition may also produce adverse effects.
  
  
  OBJECTIVE
  To determine the effect of rofecoxib, a member of the coxib class of drugs and a specific inhibitor of the COX-2 enzyme, on renal function in elderly patients.
  
  
  METHODS
  A randomized, three-period, single-dose crossover study and a randomized, parallel-group, multiple-dose study.
  
  
  METHODS
  Clinical research units.
  
  
  METHODS
  75 patients 60 to 80 years of age.
  
  
  METHODS
  In the first study, single doses of rofecoxib, 250 mg (about 5-fold to 20-fold the recommended dose); indomethacin, 75 mg; and placebo were administered to 15 patients. In the second study, multiple doses of rofecoxib, 12.5 or 25 mg/d; indomethacin, 50 mg three times daily; or placebo were administered to 60 patients. Patients in both studies received a low-sodium diet
  
  
  METHODS
  Glomerular filtration rate, creatinine clearance, and urinary and serum sodium and potassium values.
  
  
  RESULTS
  Compared with placebo, single doses of rofecoxib and indomethacin decreased the glomerular filtration rate by 0.23 m/s (P < 0.001) and 0.18 mL/s (P = 0.003), respectively. In contrast, respective decreases of 0.14, 0.13, and 0.10 mL/s were observed after multiple doses of rofecoxib, 12.5 mg/d (P = 0.019); rofecoxib, 25 mg (P = 0.029), and indomethacin (P = 0.086) were administered. Changes in creatinine clearance and serum and urinary sodium and potassium were less pronounced.
  
  
  CONCLUSIONS
  The effects of COX-2 inhibition on renal function are similar to those observed with nonselective NSAIDs. Thus, COX-2 seems to play an important role in human renal function.
authors.affiliation: Division of Nephrology, Hennepin County Medical Center and Total Renal Research, Inc., Minneapolis, Minnesota 55415, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Swan
authors.forename: D W
authors.initials: DW
authors.lastname: Rudy
authors.forename: K C
authors.initials: KC
authors.lastname: Lasseter
authors.forename: C F
authors.initials: CF
authors.lastname: Ryan
authors.forename: K L
authors.initials: KL
authors.lastname: Buechel
authors.forename: L J
authors.initials: LJ
authors.lastname: Lambrecht
authors.forename: M B
authors.initials: MB
authors.lastname: Pinto
authors.forename: S C
authors.initials: SC
authors.lastname: Dilzer
authors.forename: O
authors.initials: O
authors.lastname: Obrda
authors.forename: K J
authors.initials: KJ
authors.lastname: Sundblad
authors.forename: C P
authors.initials: CP
authors.lastname: Gumbs
authors.forename: D L
authors.initials: DL
authors.lastname: Ebel
authors.forename: H
authors.initials: H
authors.lastname: Quan
authors.forename: P J
authors.initials: PJ
authors.lastname: Larson
authors.forename: J I
authors.initials: JI
authors.lastname: Schwartz
authors.forename: T A
authors.initials: TA
authors.lastname: Musliner
authors.forename: B J
authors.initials: BJ
authors.lastname: Gertz
authors.forename: D C
authors.initials: DC
authors.lastname: Brater
authors.forename: S L
authors.initials: SL
authors.lastname: Yao
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D003404:Creatinine / Q000378:metabolism; D018592:Cross-Over Studies; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004039:Diet, Sodium-Restricted; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D007783:Lactones / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins; D011188:Potassium / Q000097:blood / Q000652:urine; D011451:Prostaglandin-Endoperoxide Synthases / Q000494:pharmacology*; D016037:Single-Blind Method; D012964:Sodium / Q000097:blood / Q000652:urine; D013450:Sulfones
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D013450:Sulfones; C116926:rofecoxib; D012964:Sodium; D003404:Creatinine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D011188:Potassium; D007213:Indomethacin