Article    Table of Contents                    Full Text of this article    PDF of this article (PDFs free after 6 months)    Summary for Patients    Figures/Tables List    Related articles in Annals  Services    Send comment/rapid response letter    Notify a friend about this article    Alert me when this article is cited    Add to Personal Archive    Download to Citation Manager    ACP Search                            Get Permissions  Google Scholar    Search for Related Content  PubMed Articles in PubMed by Author:    Swan, S. K.    Yao, S.-L.    Related Articles in PubMed    PubMed Citation    PubMed

ARTICLE

Effect of Cyclooxygenase-2 Inhibition on Renal Function in Elderly Persons Receiving a Low-Salt Diet

A Randomized, Controlled Trial

Suzanne K. Swan, MD; David W. Rudy, MD; Kenneth C. Lasseter, MD; Charles F. Ryan, PhD; Kristin L. Buechel, PA-C; Laurence J. Lambrecht, PharmD; Manuel B. Pinto, BE; Stacy C. Dilzer, RN; Olga Obrda, BS; Kimberly J. Sundblad, BSN; Carol P. Gumbs, BA; David L. Ebel, BS, RPh; Hui Quan, PhD; Patrick J. Larson, MS; Jules I. Schwartz, PharmD, MPH; Thomas A. Musliner, MD; Barry J. Gertz, MD, PhD; D. Craig Brater, MD; and Siu-Long Yao, MD

4 July 2000 | Volume 133 Issue 1 | Pages 1-9

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.

Design: A randomized, three-period, single-dose crossover study and a randomized, parallel-group, multiple-dose study.

Setting: Clinical research units.

Patients: 75 patients 60 to 80 years of age.

Intervention: 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.

Measurements: 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 mL/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.

Author and Article Information

From Hennepin County Medical Center and Total Renal Research, Inc., Minneapolis, Minnesota; Indiana University, Indianapolis, Indiana; Clinical Pharmacology Associates, Miami, Florida; PPD, Austin, Texas; and Merck Research Laboratories, Rahway, New Jersey.

Disclosure: Ms. Gumbs, Mr. Ebel, Dr. Quan, Mr. Larson, Dr. Schwartz, Dr. Musliner, Dr. Gertz, and Dr. Yao are employees of Merck and Co., Inc. Dr. Brater has served as a consultant to Merck and Co., Inc., on cyclooxygenase-2 inhibitors and renal function. Dr. Brater's role involved assistance with the design of the protocols reported in this article, assessment and interpretation of the study results reported herein, and assessment of the Merck database on rofecoxib and renal function.

Acknowledgments: The authors thank Elaine Gould for expert administrative assistance.

Grant Support: By Merck and Co., Inc.

Requests for Single Reprints: Siu-Long Yao, MD, Merck Research Laboratories, RY33-640, 126 East Lincoln Avenue, Rahway, NJ 07065-0900; e-mail, siulong_yao{at}merck.com.

Requests To Purchase Bulk Reprints (minimum, 100 copies): the Reprints Coordinator; phone, 215-351-2657; e-mail, reprints{at}mail.acponline.org.

Current Author Addresses: Dr. Swan: Division of Nephrology, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, MN 55415.

Dr. Rudy: University of Kentucky, K512 Kentucky Clinic, Lexington, KY 40536-0284.

Dr. Lasseter, Mr. Pinto, and Ms. Dilzer: Clinical Pharmacology Associates, 2060 NW 22nd Avenue, Miami, FL 33142.

Dr. Ryan: 11849 Rim Rock Trail, Austin, TX 78737.

Ms. Buechel and Dr. Lambrecht: Total Renal Research, Inc., 914 South 8th Street, Minneapolis, MN 55404-1249.

Ms. Obrda: PPD Development, 706A Ben White Boulevard, Austin, TX 78704-7016.

Ms. Sundblad: Department of Psychiatry, Indiana University School of Medicine, 1701 North Capitol Avenue, BCC-C100, Indianapolis, IN 46202.

Ms. Gumbs: Merck Research Laboratories, 126 East Lincoln Avenue (RY33-660), Rahway, NJ 07065-0980.

Mr. Ebel and Dr. Yao: Merck Research Laboratories, 126 East Lincoln Avenue (RY33-640), Rahway, NJ 07065-0980.

Dr. Quan and Mr. Larson: Merck Research Laboratories, 126 East Lincoln Avenue (RY33-404), Rahway, NJ 07065-0980.

Dr. Schwartz: Merck Research Laboratories, 126 East Lincoln Avenue (RY33-632), Rahway, NJ 07065-0980.

Dr. Musliner: Merck Research Laboratories, 126 East Lincoln Avenue (RY32-557), Rahway, NJ 07065-0980.

Dr. Gertz: Merck Research Laboratories, 126 East Lincoln Avenue (RY33-600), Rahway, NJ 07065-0980.

Dr. Brater: Department of Medicine, Indiana University School of Medicine, 545 Barnhill Drive, Emerson Hall, Room 317, Indianapolis, IN 46202-5124.

Author Contributions: Conception and design: S.K. Swan, D.W. Rudy, L.J. Lambrecht, K.J. Sundblad, H. Quan, P.J. Larson, T.A. Musliner, B.J. Gertz, D.C. Brater, S.-L. Yao.

Analysis and interpretation of the data: S.K. Swan, K.C. Lasseter, C.F. Ryan, K.L. Buechel, L.J. Lambrecht, M.B. Pinto, S.C. Dilzer, O. Obrda, C.P. Gumbs, D.L. Ebel, H. Quan, P.J. Larson, J.I. Schwartz, B.J. Gertz, D.C. Brater, S.-L. Yao.

Drafting of the article: S.K. Swan, D.C. Brater, S.-L. Yao.

Critical revision of the article for important intellectual content: S.K. Swan, D.W. Rudy, K.C. Lasseter, C.F. Ryan, K.L. Buechel, L.J. Lambrecht, M.B. Pinto, S.C. Dilzer, O. Obrda, K.J. Sundblad, C.P. Gumbs, D.L. Ebel, H. Quan, P.J. Larson, J.I. Schwartz, T.A. Musliner, B.J. Gertz, D.C. Brater, S.-L. Yao.

Final approval of the article: S.K. Swan, D.W. Rudy, K.C. Lasseter, C.F. Ryan, K.L. Buechel, L.J. Lambrecht, M.B. Pinto, S.C. Dilzer, O. Obrda, K.J. Sundblad, C.P. Gumbs, D.L. Ebel, H. Quan, P.J. Larson, J.I. Schwartz, T.A. Musliner, B.J. Gertz, D.C. Brater, S.-L. Yao.

Provision of study materials or patients: S.K. Swan, D.W. Rudy, K.C. Lasseter, C.F. Ryan, L.J. Lambrecht, O. Obrda, K.J. Sundblad, D.C. Brater.

Statistical expertise: H. Quan, P.J. Larson, S.-L. Yao.

Obtaining of funding: D.C. Brater.

Administrative, technical, or logistic support: K.C. Lasseter, C.F. Ryan, K.L. Buechel, O. Obrda, C.P. Gumbs, D.L. Ebel, D.C. Brater, S.-L. Yao.

Collection and assembly of data: S.K. Swan, C.F. Ryan, K.L. Buechel, K.J. Sundblad, H. Quan, P.J. Larson, J.I. Schwartz, D.C. Brater, S.-L. Yao.

Related articles in Annals:

Summaries for Patients
Effects of COX-2 Inhibitors, a New Class of Anti-Inflammatory Drugs, on Kidney Function in Older Patients

Annals 2000 133: 1. [Full Text]  

Letters
Cyclooxygenase-2 Inhibition and Renal Function
Alfred K. Pfister, Robert J. Crisalli, AND William H. Carter

Annals 2001 134: 1077. [Full Text]  

Letters
Cyclooxygenase-2 Inhibition and Renal Function
Andrew Whelton

Annals 2001 134: 1077-1078. [Full Text]  

Letters
Cyclooxygenase-2 Inhibition and Renal Function
Suzanne K. Swan AND D. Craig Brater

Annals 2001 134: 1078. [Full Text]  

This article has been cited by other articles:

				E. A. Jaimes, M.-S. Zhou, D. D. Pearse, L. Puzis, and L. Raij Upregulation of cortical COX-2 in salt-sensitive hypertension: role of angiotensin II and reactive oxygen species Am J Physiol Renal Physiol, February 1, 2008; 294(2): F385 - F392. [Abstract] [Full Text] [PDF]

				J. I. Schwartz, C. Thach, K. C. Lasseter, J. Miller, D. Hreniuk, D. A. Hilliard, K. M. Snyder, B. J. Gertz, and K. M. Gottesdiener Effects of Etoricoxib and Comparator Nonsteroidal Anti-Inflammatory Drugs on Urinary Sodium Excretion, Blood Pressure, and Other Renal Function Indicators in Elderly Subjects Consuming a Controlled Sodium Diet J. Clin. Pharmacol., December 1, 2007; 47(12): 1521 - 1531. [Abstract] [Full Text] [PDF]

				D. Sankaran, N. Bankovic-Calic, M. R. Ogborn, G. Crow, and H. M. Aukema Selective COX-2 inhibition markedly slows disease progression and attenuates altered prostanoid production in Han:SPRD-cy rats with inherited kidney disease Am J Physiol Renal Physiol, September 1, 2007; 293(3): F821 - F830. [Abstract] [Full Text] [PDF]

				W. Koppert, K. Frotsch, N. Huzurudin, W. Boswald, N. Griessinger, V. Weisbach, R. E. Schmieder, and J. Schuttler The Effects of Paracetamol and Parecoxib on Kidney Function in Elderly Patients Undergoing Orthopedic Surgery Anesth. Analg., November 1, 2006; 103(5): 1170 - 1176. [Abstract] [Full Text] [PDF]

				S. Chaiamnuay, J. J. Allison, and J. R. Curtis Risks versus benefits of cyclooxygenase-2-selective nonsteroidal antiinflammatory drugs. Am. J. Health Syst. Pharm., October 1, 2006; 63(19): 1837 - 1851. [Abstract] [Full Text] [PDF]

				L. Warford-Woolgar, C. Y.-C. Peng, J. Shuhyta, A. Wakefield, D. Sankaran, M. Ogborn, and H. M. Aukema Selectivity of cyclooxygenase isoform activity and prostanoid production in normal and diseased Han:SPRD-cy rat kidneys Am J Physiol Renal Physiol, April 1, 2006; 290(4): F897 - F904. [Abstract] [Full Text] [PDF]

				R. C. Harris and M. D. Breyer Update on Cyclooxygenase-2 Inhibitors Clin. J. Am. Soc. Nephrol., March 1, 2006; 1(2): 236 - 245. [Abstract] [Full Text] [PDF]

				E. M. Antman, D. DeMets, and J. Loscalzo Cyclooxygenase Inhibition and Cardiovascular Risk Circulation, August 2, 2005; 112(5): 759 - 770. [Full Text] [PDF]

				D. L. Simmons, R. M. Botting, and T. Hla Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition Pharmacol. Rev., September 1, 2004; 56(3): 387 - 437. [Abstract] [Full Text] [PDF]

				T. D. WARNER and J. A. MITCHELL Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic FASEB J, May 1, 2004; 18(7): 790 - 804. [Abstract] [Full Text] [PDF]

				G. L. Braden, M. H. O'shea, J. G. Mulhern, and M. J. Germain Acute renal failure and hyperkalaemia associated with cyclooxygenase-2 inhibitors Nephrol. Dial. Transplant., May 1, 2004; 19(5): 1149 - 1153. [Abstract] [Full Text] [PDF]

				K. L. Therland, J. Stubbe, H. C. Thiesson, P. D. Ottosen, S. Walter, G. L. Sorensen, O. Skott, and B. L. Jensen Cycloxygenase-2 Is Expressed in Vasculature of Normal and Ischemic Adult Human Kidney and Is Colocalized with Vascular Prostaglandin E2 EP4 Receptors J. Am. Soc. Nephrol., May 1, 2004; 15(5): 1189 - 1198. [Abstract] [Full Text] [PDF]

				G. K Sandhu and C. A Heyneman Nephrotoxic Potential of Selective Cyclooxygenase-2 Inhibitors Ann. Pharmacother., April 1, 2004; 38(4): 700 - 704. [Abstract] [Full Text] [PDF]

				H.-F. Cheng and R. C. Harris Cyclooxygenases, the Kidney, and Hypertension Hypertension, March 1, 2004; 43(3): 525 - 530. [Abstract] [Full Text] [PDF]

				V K Podichetty, D J Mazanec, and R S Biscup Chronic non-malignant musculoskeletal pain in older adults: clinical issues and opioid intervention Postgrad. Med. J., November 1, 2003; 79(937): 627 - 633. [Abstract] [Full Text] [PDF]

				M. M Verrico, R. J Weber, T. P McKaveney, N. T Ansani, and A. L Towers Adverse Drug Events Involving COX-2 Inhibitors Ann. Pharmacother., September 1, 2003; 37(9): 1203 - 1213. [Abstract] [Full Text] [PDF]

				V. L. Ghafoor Treatment of Chronic Pain Journal of Pharmacy Practice, August 1, 2003; 16(4): 249 - 260. [Abstract] [PDF]

				V. L. Ghafoor Management of Painful Conditions in the Elderly Journal of Pharmacy Practice, August 1, 2003; 16(4): 276 - 283. [Abstract] [PDF]

				N. M. Gajraj Cyclooxygenase-2 Inhibitors Anesth. Analg., June 1, 2003; 96(6): 1720 - 1738. [Full Text] [PDF]

				C J Hawkey and M J S Langman Non-steroidal anti-inflammatory drugs: overall risks and management. Complementary roles for COX-2 inhibitors and proton pump inhibitors Gut, April 1, 2003; 52(4): 600 - 608. [Abstract] [Full Text] [PDF]

				T. P. Connolly Cyclooxygenase-2 Inhibitors in Gynecologic Practice Clin. Med. Res., April 1, 2003; 1(2): 105 - 110. [Abstract] [Full Text] [PDF]

				A. Reinacher-Schick, A. Schoeneck, U. Graeven, I. Schwarte-Waldhoff, and W. Schmiegel Mesalazine causes a mitotic arrest and induces caspase-dependent apoptosis in colon carcinoma cells Carcinogenesis, March 1, 2003; 24(3): 443 - 451. [Abstract] [Full Text] [PDF]

				E. Niederberger, I. Tegeder, C. Schafer, M. Seegel, S. Grosch, and G. Geisslinger Opposite Effects of Rofecoxib on Nuclear Factor-kappa B and Activating Protein-1 Activation J. Pharmacol. Exp. Ther., March 1, 2003; 304(3): 1153 - 1160. [Abstract] [Full Text] [PDF]

				F. F. Immer, A. S. Immer-Bansi, N. Trachsel, P. A. Berdat, V. Eigenmann, M. Curatolo, and T. P. Carrel Pain treatment with a COX-2 inhibitor after coronary artery bypass operation: a randomized trial Ann. Thorac. Surg., February 1, 2003; 75(2): 490 - 495. [Abstract] [Full Text] [PDF]

				F. K.L. Chan, L. C.T. Hung, B. Y. Suen, J. C.Y. Wu, K. C. Lee, V. K.S. Leung, A. J. Hui, K. F. To, W. K. Leung, V. W.S. Wong, et al. Celecoxib versus Diclofenac and Omeprazole in Reducing the Risk of Recurrent Ulcer Bleeding in Patients with Arthritis N. Engl. J. Med., December 26, 2002; 347(26): 2104 - 2110. [Abstract] [Full Text] [PDF]

				D. R. MEHLISCH The efficacy of combination analgesic therapy in relieving dental pain J Am Dent Assoc, July 1, 2002; 133(7): 861 - 871. [Abstract] [Full Text] [PDF]

				C J Hawkey Cyclooxygenase inhibition: between the devil and the deep blue sea Gut, May 1, 2002; 50(90003): iii25 - 30. [Abstract] [Full Text] [PDF]

				M. Miyataka, K. A. Rich, M. Ingram, T. Yamamoto, and R. J. Bing Nitric Oxide, Anti-Inflammatory Drugs on Renal Prostaglandins and Cyclooxygenase-2 Hypertension, March 1, 2002; 39(3): 785 - 789. [Abstract] [Full Text] [PDF]

				G. A. FitzGerald and C. Patrono The Coxibs, Selective Inhibitors of Cyclooxygenase-2 N. Engl. J. Med., August 9, 2001; 345(6): 433 - 442. [Full Text] [PDF]

				M. D. Fernandez, J. L. Z. Garcia, F. D. Garcia, S. Gupta, C. Bombardier, L. Laine, and A. Reicin Upper Gastrointestinal Toxicity of Rofecoxib and Naproxen N. Engl. J. Med., May 3, 2001; 344(18): 1398 - 1399. [Full Text] [PDF]

				V. Rozenfeld, L. Chagan, and E. Kleyman The Year in Review: Rheumatology Journal of Pharmacy Practice, February 1, 2001; 14(1): 54 - 69. [Abstract] [PDF]

				D. R. Lichtenstein and M. M. Wolfe COX-2-Selective NSAIDs: New and Improved? JAMA, September 13, 2000; 284(10): 1297 - 1299. [Full Text] [PDF]

				B. H. Chen COX-2 inhibitors and renal function in elderly people Can. Med. Assoc. J., September 1, 2000; 163(5): 604 - 604. [Full Text] [PDF]

				General Medicine: COX-2 Inhibitors: Not Perfectly Safe Journal Watch Dermatology, August 28, 2000; 2000(828): 8 - 8. [Full Text]

				COX-2 Inhibitors: Not Perfectly Safe Journal Watch (General), July 14, 2000; 2000(714): 1 - 1. [Full Text]