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Cyclo-Oxygenase-2 Inhibitors and the Kidney

A Case for Caution

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Abstract

Cyclo-oxygenase (COX) is one of the key enzymes in the biosynthesis of prostaglandins. Two isoforms of this enzyme COX-1 and COX-2 are known to exist. Among other functions, prostaglandins play an important role in the protection of the gastric mucosa and maintenance of renal function in pathophysiological conditions which would otherwise threaten it. Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandin synthesis, resulting in gastric mucosal injury and renal dysfunction in susceptible individuals. The recent introduction of selective COX-2 inhibitors, celecoxib and rofecoxib, appear to induce less gastrointestinal morbidity. Although conclusive data are still lacking, there is evidence to suggest that COX-2 antagonists may be capable of causing some of the same renal syndromes seen in association with the older, less selective NSAIDs.

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References

  1. Baum C, Kennedy DL, Forbes MB. Utilization of nonsteroidal antiinflammatory drugs. Arthritis Rheum 1985; 28: 686–92

    Article  PubMed  CAS  Google Scholar 

  2. Wolfe MM, Licthenstein DR, Singh G. Medical progress: gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med 1999; 340: 1888–99

    Article  PubMed  CAS  Google Scholar 

  3. Peloso P. NSAIDS: a Faustian bargain. Am J Nurs 2000; 100: 34–9

    PubMed  CAS  Google Scholar 

  4. Clive DM, Stoff JS. Renal syndromes associated with nonsteroidal antiinflammatory drugs. N Engl J Med 1984; 310: 563–72

    Article  PubMed  CAS  Google Scholar 

  5. Dunn MJ. Nonsteroidal antiinflammatory drugs and renal function. Ann Rev Med 1984; 34: 411–28

    Article  Google Scholar 

  6. Palmer BF. Renal complications associated with use of nonsteroidal antiinflammatory drugs. J Investig Med 1995; 43: 516–33

    PubMed  CAS  Google Scholar 

  7. Zimran A. Kramer M. Incidence of hyperkalemia induced by indomethacin in a hospital population. BMJ 1985; 291: 107–8

    Article  PubMed  CAS  Google Scholar 

  8. Perneger TV, Whelton PK, Klag MJ. Risk of kidney failure associated with the use of acetominophen, aspirin, and nonsteroidal antiinflammatory drugs. N Engl J Med 1994; 331: 1675–9

    Article  PubMed  CAS  Google Scholar 

  9. Stillman MT, Napier J, Blackshear JL. adverse effects of nonsteroidal anti-inflammatory drugs on the kidney. Med Clin North Am 1984; 65: 371–85

    Google Scholar 

  10. Golden BD, Abramson SB. Selective COX-2 inhibitors for arthritis: from bench to bedside. Rhema 21st, Cutting Edge Reports 1999: 1–10

    Google Scholar 

  11. Crofford LF, Lipsky PE, Brooks P, et al. basic biology and clinical application of specific cyclooxygenase-2 inhibitors. Arthritis Rheum 2000; 43: 4–13

    Article  PubMed  CAS  Google Scholar 

  12. Ichitani Y, Holmberg K, Maunsbach AB, et al. Cyclooxygenase-1 and cyclooxygenase-2 expression in rat kidney and adrenal gland after stimulation with systemic lipopolysaccharide: in situ hybridization and immunocytochemical studies. Cell Tissue Res 2001; 303: 235–52

    Article  PubMed  CAS  Google Scholar 

  13. Schaefers HJ, Goppelt-Struebe M. Interference of corticosteroids with prostaglandin E2 synthesis at the level of cyclooxygenase-2 mRNA expression in kidney cells. Biochem Pharmacol 1996; 52: 1415–21

    Article  PubMed  CAS  Google Scholar 

  14. Vio CP, An SJ, Cespedes C, et al. Induction of cyclooxygenase-2 in thick ascending limb cells by adrenalectomy. J Am Soc Nephrol 2001; 12: 649–58

    PubMed  CAS  Google Scholar 

  15. Stichtentoth DO, Frolich JC. COX-2 and the kidneys. Curr Pharm Design 2000; 6: 1737–53

    Article  Google Scholar 

  16. Harris RC. Cyclooxygenase-2 in the kidney. J Am Soc Nephrol 2000; 11: 2387–94

    PubMed  CAS  Google Scholar 

  17. Norwood VF, Morham SG, Smithies O. Postnatal development and progression of renal dysplasia in cyclooxygenase-2 null mice. Kidney Int 2000; 58: 2291–300

    Article  PubMed  CAS  Google Scholar 

  18. Yang T, Singh I, Pham H, et al. Regulation of cyclooxygenase expression in the kidney by dietary salt intake. Am J Physiol Renal Physiol 1998; 274: F481–9

    CAS  Google Scholar 

  19. Harris RC, McKanna JA, Akai Y, et al. Cyclo-oxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction. J Clin Invest 1994; 94: 2504–10

    Article  PubMed  CAS  Google Scholar 

  20. Lorenz JN, Greenberg SG. The macula densa of rat kidney and increases with salt restriction. Semin Nephrol 1993; 13: 531–40

    PubMed  CAS  Google Scholar 

  21. Harding P, Sigmon DH, Alfie ME, et al. Cyclo-oxygenase-2 mediates increased renal renin content induced by low sodium diet. Hypertension 1997; 29: 297–302

    Article  PubMed  CAS  Google Scholar 

  22. Harding P, Carretero OA, Beierwlates WH. Chronic cyclooxygenase-2 inhibition blunts low sodium-stimulated renin without changing renal hemodynamics. J Hypertens 2000; 18: 1107–13

    Article  PubMed  CAS  Google Scholar 

  23. Cheng HF, Wang JL, Zhang MZ, et al. Genetic deletion of COX-2 prevents increased renin expression in response to ACE inhibition. Am J Physiol Renal Physiol 2001; 280: F449–56

    PubMed  CAS  Google Scholar 

  24. Wang JL, Cheng HF, Harris RC. Cyclo-oxygenase-2 inhibition decreases renin content and lowers blood pressure in a model of renovascular hypertension. Hypertension 1999, 34: 96–101

    Article  PubMed  CAS  Google Scholar 

  25. Rodriguez F, Llinas MT, Gonzalez JD, et al. Renal changes induced by a cyclooxygenase-2 inhibitor during normal and low sodium intake. Hypertension 2000; 36: 276–81

    Article  PubMed  CAS  Google Scholar 

  26. Abassi Z, Brodsky S, Gealekman O, et al. Intrarenal expression and distribution of cyclooxygenase isoforms in rats with experimental heart failure. Am J Physiol Renal Physiol 2001; 280: F43–F53

    PubMed  CAS  Google Scholar 

  27. Tomasoni S, Noris M, Zappella S, et al. Upregulation of renal and systemic cyclooxygenase-2 in patients with active lupus nephritis. J Am Soc Nephrol 1998, 9; 1202–12

    PubMed  CAS  Google Scholar 

  28. Bosch-Marce M, Claria J, Titos E, et al. Selective inhibition of cyclooxygenase 2 spares renal function and prostaglandin synthesis in cirrhotic rats with ascites. Gastroenterology 1999; 116: 1167–75

    Article  PubMed  CAS  Google Scholar 

  29. Gross JM, Dwyer JE, Knox FG. Natiuretic respone to increased pressure is preserved with COX-2 inhibitors. Hypertension 1999; 34: 1163–7

    Article  PubMed  CAS  Google Scholar 

  30. Blume C, Heise G, Muhlfeld A, et al. Effect of flosulide, a selective cyclooxygenase-2 inhibitor, on passive Heymann nephritis in the rat. Kidney Int 1999; 56(5): 1770–8

    Article  PubMed  CAS  Google Scholar 

  31. Wang JL, Cheng HF, Shappell S, et al. A selective cyclooxygenase-2 inhibitor decreases proteinuria and retards progressive renal injury in rats. Kidney Int 2000; 57: 2334–42

    Article  PubMed  CAS  Google Scholar 

  32. Wang JL, Cheng HF, Zhang MZ, et al. Selective increase of cyclooxygenase-2 expression in a model of renal ablation. Am J Physiol 1998; 275: F613–F622

    PubMed  CAS  Google Scholar 

  33. Komers R, Lindsley JN, Oyama TT, et al. Immunohistochemical and functional correlations of renal cyclooxygenase-2 in experimental diabetes. J Clinical Invest 2001; 107: 889–98

    Article  CAS  Google Scholar 

  34. Swan SK, Rudy DW, Lasseter KC, et al. Effect of cyclooxygenase-2 inhibition on renal function in elderly persons receiving a low-salt diet. Ann Intern Med 2000; 133: 1–9

    PubMed  CAS  Google Scholar 

  35. Rossat J, Maillare M, Nussberger J, et al. Renal effects of selective cyclooxygenase-2 inhibition in normotensive salt-depleted subjects. Clin Pharmacol Ther 1999; 66: 76–84

    Article  PubMed  CAS  Google Scholar 

  36. Whelton A, Schulman G, Wallemark C, et al. Effects of celecoxib and naproxen on renal function in the elderly. Arch Intern Med 2000; 160: 1465–70

    Article  PubMed  CAS  Google Scholar 

  37. Bevis PJR, Bird HA, Lapham G. An open study to assess the safety and tolerability of meloxicam 15 mg in subject with rhematic disease and mild renal impairment. Br J Rheumatol 1996; 35Suppl. 1: 56–60

    Article  PubMed  CAS  Google Scholar 

  38. Catella-Lawson F, McAdam B, Morrison BW, et al. Effects of specific inhibition of cyclooxygenase-2 on sodium balance, hemodynamics, and vasoactive eicosanoids. J Pharmacol Exp Ther 1999; 289: 735–41

    PubMed  CAS  Google Scholar 

  39. Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthrits and rheumatoid arthritis. JAMA 2000; 284: 1247–55

    Article  PubMed  CAS  Google Scholar 

  40. Whelton A, Maurath CJ, Verburg KM, et al. Renal safety and tolerability of clelcoxib, a novel cyclooxygenase-2 inhibitor. Am J Therapeut 2000; 7: 159–72

    Article  CAS  Google Scholar 

  41. Perrazella MA, Eras J. Are selective COX-2 inhibitors nephrotoxic? Am J Kidney Dis 2000; 5: 937–40

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Division of Renal Medicine, University of Massachusetts Medical School, Worcester, 01655, Massachusetts, USA

    Gary Noroian & David Clive

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  1. Gary Noroian
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  2. David Clive
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Noroian, G., Clive, D. Cyclo-Oxygenase-2 Inhibitors and the Kidney. Drug-Safety 25, 165–172 (2002). https://doi.org/10.2165/00002018-200225030-00003

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  • DOI: https://doi.org/10.2165/00002018-200225030-00003

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