Pediatric Nephrology

, Volume 21, Issue 12, pp 1893–1897 | Cite as

Nephrotoxicity with cyclooxygenase 2 inhibitor use in children

  • Jeffery T. Fletcher
  • Nicole Graf
  • Anthony Scarman
  • Hamda Saleh
  • Stephen I. Alexander
Brief Report

Abstract

The nephrotoxic potential of anti-inflammatory drugs alone and in compound preparations has been known for over fifty years. Nephrotoxicity associated with selective cyclooxygenase 2 (COX-2) inhibitor use is reported in adult patients but not in children. We present here the first report of reversible acute renal failure associated with the COX-2 inhibitor rofecoxib (Vioxx) in three children. Patient 1, an 18 month old girl with neonatal Bartter syndrome, developed acute renal failure with a peak creatinine of 1.9 mg/dl (164 μmol/l) and severe hyperkalemic metabolic acidosis. Patient 2, a 14 year old boy with a history of rheumatic fever, developed acute renal failure with a peak creatinine of 2.7 mg/dl (240 µmol/l). While patient 3, a healthy 14 year old girl, developed acute renal failure and tubulointerstitial nephritis confirmed on renal biopsy with a peak creatinine of 3.3 mg/dl (287 µmol/L). All children had been taking non-selective non-steroidal anti-inflammatory drugs (NSAID’s) immediately prior to rofecoxib use. Renal function returned to normal within one week in all three patients and has remained normal at follow-up. This paper highlights the nephrotoxic risk of COX-2 inhibitor use in the pediatric population.

Keywords

Analgesic nephropathy ARF COX-2 inhibitors Kidney Pediatrics 

References

  1. 1.
    Nanra RS (1993) Analgesic nephropathy in the 1990’s - an Australian perspective. Kidney Int Suppl 42:S86–S92PubMedGoogle Scholar
  2. 2.
    Whelton A (1999) Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications. Am J Med 106(5B):13S–24SPubMedCrossRefGoogle Scholar
  3. 3.
    Rosert JA, Fischer EA (2003) Acute interstitial nephritis. In: Johnson RJ, Feehally J (eds) Comprehensive clinical nephrology. Harcourt Publishers Limited, Toronto, pp 769–777Google Scholar
  4. 4.
    Moghal NE, Hegde S, Eastham KM (2004) Ibuprofen and acute renal failure in a toddler. Arch Dis Child 89:276–277PubMedCrossRefGoogle Scholar
  5. 5.
    Wattad A, Feehan T, Shepard FM, Youngberg G (1994) A unique complication of nonsteroidal antiinflammatory drug use. Pediatrics 93:693PubMedGoogle Scholar
  6. 6.
    Barkin RL, Buvanendran A (2004) Focus on the COX-1 and COX-2 agents: renal events of nonsteroidal and anti-inflammatory drugs-NSAIDs. Am J Therapeut 11:124–129CrossRefGoogle Scholar
  7. 7.
    Chan FKL, Hung LCT, Suen BY, Wu JCY, Lee KC, Leung VKS, Hui AJ, To KF, Leung WK, Wong VWS, Chung S, Sung JY (2002) Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl J Med 347:2104–2110PubMedCrossRefGoogle Scholar
  8. 8.
    Papaioannides D, Bouropoulos C, Sinapides D, Korantzopoulos P, Akritidis N (2001) Acute renal dysfunction associated with selective COX-2 inhibitor therapy. Int Urol Nephrol 33:609–611PubMedCrossRefGoogle Scholar
  9. 9.
    Rocha JL, Fernandez-Alonso J (2001) Acute tubulointerstitial nephritis associated with the selective COX-2 enzyme inhibitor, rofecoxib. Lancet 357:1946–1947PubMedCrossRefGoogle Scholar
  10. 10.
    Esteve JB, Launay-Vacher V, Brocheriou I, Grimaldi A, Izzedine H (2005) Cox-2 inhibitors and acute interstitial nephritis: a case report and review of the literature. Clin Nephrol 63:385–389PubMedGoogle Scholar
  11. 11.
    Reinalter SC, Jeck N, Brochhausen C, Watzer B, Nusing RM, Seyberth HW, Kornhoff M (2002) Role of cyclooxygenase-2 in hyper prostaglandin E syndrome/antenatal Bartter syndrome. Kidney Int 62:253–260PubMedCrossRefGoogle Scholar
  12. 12.
    Haas NA, Nossal R, Schneider CH, Lewin MA, Ocker V, Holder M, Uhlemann, F (2003) Successful management of an extreme example of neonatal hyper prostaglandin-E syndrome (Bartters’ syndrome) with the new cyclooxygenase-2 inhibitor rofecoxib. Pedaitr Crit Care Med 4:249–251CrossRefGoogle Scholar
  13. 13.
    Vaisbich MH, Fujimura MD, Koch VH (2004) Bartter syndrome: benefits and side effects of long-term treatment. Pediatr Nephrol 19:858–863PubMedCrossRefGoogle Scholar
  14. 14.
    Zhao SZ, Reynolds MW, Lefkowith JB, Whelton A, Arellano FM (2001) A comparison of renal-related adverse drug reactions between rofecoxib and celecoxib, based on the World Health Organisation/Uppsala Monitoring Centre safety database. Clin Therapeut 23:1478–1491CrossRefGoogle Scholar
  15. 15.
    Swan S, Rudy DW, Lasseter KC, Ryan CF, Buechel KL, Lambrecht L, Pinto MB, Dilzer SC, Obrda O, Sundblad KJ, Gumbs CP, Ebel DL, Qua H, Larson PJ, Schwartz JI, Musliner TA, Gertz BJ, Brater DC, Yao SL (2000) Effect of cyclooxygenase-2 inhibition on renal function in elderly persons receiving a low-salt diet. A randomized controlled trial. Ann Int Med 133:1–9PubMedGoogle Scholar
  16. 16.
    Norwood VF, Morham SG, Smithies OS (2000) Postnatal development and progression of renal dysplasia in cyclooxygenase-2 null mice. Kidney Int 58:2291–2300PubMedCrossRefGoogle Scholar
  17. 17.
    Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, Day R, Ferraz MB, Hawkey CJ, Hochberg MC, Kvien TK, Schnitzer TJ, VIGOR Study Group (2000) Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med 343:1520–1528PubMedCrossRefGoogle Scholar
  18. 18.
    Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, Makuch R, Eisen G, Agrawal NM, Stenson WF, Burr AM, Zhao WW, Kent JD, Lefkowith JB, Verburg KM, Geis GS (2000) Gastrointestinal toxicity with celecoxib vs Nonsteroidal Anti-Inflammatory drugs for osteoarthritis and rheumatoid arthritis. The CLASS Study: a randomized controlled trial. JAMA 284:1247–1255PubMedCrossRefGoogle Scholar
  19. 19.
    Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, Lines C, Riddell R, Morton D, Lanas A, Konstam MA, Baron JA (2005) Cardiovascular events associated with Rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 352:1092–1102PubMedCrossRefGoogle Scholar
  20. 20.
    Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P, Anderson WF, Zauber A, Hawk E, Bertagnolli M (2005) Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 352:2581–2588PubMedCrossRefGoogle Scholar
  21. 21.
    Nussmeir NA, Whelton A, Brown M, Langford RM, Hoeft A, Parlow JL, Boyce SW, Verburg KM (2005) Complications of the cox-2 inhibitors Parecoxib and Valdecoxib after cardiac surgery. N Engl J Med 352:1081–1091CrossRefGoogle Scholar
  22. 22.
    Kerr SJ, Mant A, Horn FE, McGeechan K, Sayer GP (2003) Lessons from early large scale adoption of celecoxib and rofecoxib by Australian general practitioners. Med J Aust 179:403–407PubMedGoogle Scholar
  23. 23.
    Salazar JC (2003) Pediatric clinical trial experience: government, child, parent and physician’s perspective. Pediatr Infect Dis J 22:1124–1127PubMedGoogle Scholar
  24. 24.
    Caldwell PH, Murphy SB, Butow PN, Craig JC (2004) Clinical trials in children. Lancet 364:803–811PubMedCrossRefGoogle Scholar
  25. 25.
    Young D (2005) FDA labors over NSAID decisions: panel suggests COX-2 inhibitors stay available. Am J Health Syst Pharm 62:668–672PubMedGoogle Scholar

Copyright information

© IPNA 2006

Authors and Affiliations

  • Jeffery T. Fletcher
    • 1
    • 2
  • Nicole Graf
    • 3
  • Anthony Scarman
    • 1
  • Hamda Saleh
    • 4
  • Stephen I. Alexander
    • 1
    • 2
    • 5
  1. 1.Centre for Kidney ResearchThe Children’s Hospital at WestmeadWestmeadAustralia
  2. 2.Department of Paediatrics and Child HealthUniversity of SydneySydneyAustralia
  3. 3.Department of HistopathologyThe Children’s Hospital at WestmeadWestmeadAustralia
  4. 4.Department of Nuclear MedicineThe Children’s Hospital at WestmeadWestmeadAustralia
  5. 5.Centre for Kidney Research, Department of NephrologyThe Children’s Hospital at WestmeadWestmeadAustralia

Personalised recommendations