Proton pump inhibitors: acute interstitial nephritis and other renal effects

  • Ursula C. Brewster
  • Mark A. Perazella

Proton pump inhibitors (PPIs) were introduced in 1989 with the development of omeprazole. Since then, they have become one of the most widely prescribed class of drugs on the market today. Over 43 million prescriptions were written for anti-ulcer therapy in the US in 2005 [1]. Currently, there are five PPIs available in the United States and Europe: esomeprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole. Their safety and efficacy profile is excellent, which has been the major factor leading to over 8 billion dollars in sales in 2005; a considerable sum given that omeprazole has been available since 2003 [2]. However, renal complications do occur and it is important that they are recognized. Reported events include rare hyponatremia, drug-drug interactions and acute interstitial nephritis (AIN). There are, as of yet, no data on chronic interstitial disease resulting from these agents. However, it is certainly conceivable that long standing AIN may transition to chronic interstitial nephritis and end-stage renal disease.


Chronic Kidney Disease Proton Pump Inhibitor Calcineurin Inhibitor Interstitial Nephritis Nephrol Dial Transplant 
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  1. 1.
    Diamanti F. In; 2006:Personal Communication from TAP Pharmaceuticals.Google Scholar
  2. 2.
    New Drugs are not always innovative, just formulas that mirror each other and have been tweaked to gain patient protection and turn big profits. 2005. (Accessed Feb 7, 2007, at
  3. 3.
    Howden CW RJ. Omeprazole, a gastric ‘proton pump inhibitor’: lack of effect on renal handling of electrolytes and urinary acidification. Eur J Clin Pharmacol 1984;26:639-40.CrossRefPubMedGoogle Scholar
  4. 4.
    Sanborn K, ed. Physicians Desk Reference. 61 ed. Montvale, NJ: Thompson PDR; 2007.Google Scholar
  5. 5.
    Ishizaki T, Horai Y. Review article: cytochrome P450 and the metabolism of proton pump inhibitors--emphasis on rabeprazole. Aliment Pharmacol Ther 1999;13 Suppl 3:27–36.CrossRefPubMedGoogle Scholar
  6. 6.
    Kaloustian E, Veyssier P. [Severe hyponatremia: possible role of omeprazole]. Presse Med 1992;21(19):907-8.PubMedGoogle Scholar
  7. 7.
    Gonthier R, Bouchou K , Guy C, Cathebras P, Rousset H. [Severe hyponatremia induced by meprazole]. Presse Med 1993;22(4):176.PubMedGoogle Scholar
  8. 8.
    Melville C, Shah A, Matthew D, Milla P. Electrolyte disturbance with omeprazole therapy. Eur J Pediatr 1994;153(1):49–51.PubMedGoogle Scholar
  9. 9.
    Durst RY, Pipek R, Levy Y. Hyponatremia caused by omeprazole treatment. Am J Med 1994;97(4):400-1.CrossRefPubMedGoogle Scholar
  10. 10.
    Shiba S, Sugiura K, Ebata A, et al. Hyponatremia with consciousness disturbance caused by omeprazole administration. A case report and literature review. Dig Dis Sci 1996;41(8):1615-7.CrossRefPubMedGoogle Scholar
  11. 11.
    Mennecier D, Ceppa F, Gidenne S, Vergeau B. Hyponatremia with consciousness disturbance associated with esomeprazole. Ann Pharmacother 2005;39(4):774-5.CrossRefPubMedGoogle Scholar
  12. 12.
    Castot A, Bidault I, Dahan R, Efthymiou ML. [Evaluation of unexpected and toxic effects of omeprazole (Mopral) reported to the regional centers of pharmacovigilance during the first 22 postmarketing months]. Therapie 1993;48(5):469-74.PubMedGoogle Scholar
  13. 13.
    Christians U, Schmidt G, Bader A, et al. Identification of drugs inhibiting the in vitro metabolism of tacrolimus by human liver microsomes. Br J Clin Pharmacol 1996;41(3):187-90.CrossRefPubMedGoogle Scholar
  14. 14.
    Lorf T, Ramadori G, Ringe B, Schworer H. Pantoprazole does not affect cyclosporin A blood concentration in kidney-transplant patients. Eur J Clin Pharmacol 2000;55(10):733-5.CrossRefPubMedGoogle Scholar
  15. 15.
    Pascual J, Marcen R, Orea OE, et al. Interaction between omeprazole and tacrolimus in renal allograft recipients: a clinical-analytical study. Transplant Proc 2005;37(9):3752-3.CrossRefPubMedGoogle Scholar
  16. 16.
    Itagaki F, Homma M, Yuzawa K, Fukao K, Kohda Y. Drug interaction of tacrolimus and proton pump inhibitors in renal transplant recipients with CYP2C19 gene mutation. Transplant Proc 2002;34(7):2777-8.CrossRefPubMedGoogle Scholar
  17. 17.
    Ruffenach SJ, Siskind MS, Lien YH. Acute interstitial nephritis due to omeprazole. Am J Med 1992;93(4):472-3.CrossRefPubMedGoogle Scholar
  18. 18.
    Post AT VG, Zanen AL. Reversible renal failure after treatment with omeprazole. Neth J Med 2000;57:58-61.PubMedCrossRefGoogle Scholar
  19. 19.
    Myers RP, McLaughlin K, Hollomby DJ. Acute interstitial nephritis due to omeprazole. Am J Gastroenterol 2001;96(12):3428-31.CrossRefPubMedGoogle Scholar
  20. 20.
    Portera-Cailliau C SA. Acute Interstitial Nephritis Due to Omeprazole. Annals of Long-Term Care 1999;7(5):206-7.Google Scholar
  21. 21.
    Wall CA, Gaffney EF, Mellotte GJ. Hypercalcaemia and acute interstitial nephritis associated with omeprazole therapy. Nephrol Dial Transplant 2000;15(9):1450-2.CrossRefPubMedGoogle Scholar
  22. 22.
    Geetha D. Omeprazole-induced acute interstitial nephritis. Am J Gastroenterol 1999;94(11):3375-6.CrossRefPubMedGoogle Scholar
  23. 23.
    Torregrosa E, Rovira RE, Calvo C, Hernandez-Jaras J, Maduell F, Garcia H. [Acute interstitial nephritis associated with omeprazole therapy]. Nefrologia 2004;24 Suppl 3:61-3.PubMedGoogle Scholar
  24. 24.
    Torpey N, Barker T, Ross C. Drug-induced tubulo-interstitial nephritis secondary to proton pump inhibitors: experience from a single UK renal unit. Nephrol Dial Transplant 2004;19(6):1441-6.CrossRefPubMedGoogle Scholar
  25. 25.
    Simpson IJ MM, Pilmore H, Manley P, Williams L, Thein H, Voss D. Proton Pump Inhibitor and acute interstitial nephritis: Report and anlysis of 15 cases. Nephrology 2006;11:381-5.Google Scholar
  26. 26.
    Geevasinga N, Coleman PL, Roger SD. Rabeprazole-induced acute interstitial nephritis. Nephrology (Carlton) 2005;10(1):7-9.CrossRefGoogle Scholar
  27. 27.
    Geevasinga N, Coleman PL, Webster AC, Roger SD. Proton pump inhibitors and acute interstitial nephritis. Clin Gastroenterol Hepatol 2006;4(5):597–604.CrossRefPubMedGoogle Scholar
  28. 28.
    Christensen PB, Albertsen KE, Jensen P. Renal failure after omeprazole. Lancet 1993;341(8836):55.CrossRefPubMedGoogle Scholar
  29. 29.
    Assouad M, Vicks SL, Pokroy MV, Willcourt RJ. Recurrent acute interstitial nephritis on rechallenge with omeprazole. Lancet 1994;344(8921):549.CrossRefPubMedGoogle Scholar
  30. 30.
    Gronich JH SE, Stein HD Sirota RA, Yudis M. Omeprazole related acute interstitial nephritis (AIN) with omeprazole (Abstract). JASN 1994;5:394.Google Scholar
  31. 31.
    Brewster UC, Perazella MA. Acute kidney injury following proton pump inhibitor therapy. Kidney Int 2006.Google Scholar
  32. 32.
    Ra A, Tobe SW. Acute interstitial nephritis due to pantoprazole. Ann Pharmacother 2004;38(1):41-5.CrossRefPubMedGoogle Scholar
  33. 33.
    Buysen JG, Houthoff HJ, Krediet RT, Arisz L. Acute interstitial nephritis: a clinical and morphological study in 27 patients. Nephrol Dial Transplant 1990;5(2):94-9.PubMedGoogle Scholar
  34. 34.
    Clarkson MR, Giblin L, O’Connell FP, et al. Acute interstitial nephritis: clinical features and response to corticosteroid therapy. Nephrol Dial Transplant 2004;19(11):2778-83.CrossRefPubMedGoogle Scholar
  35. 35.
    Davison AM, Jones CH. Acute interstitial nephritis in the elderly: a report from the UK MRC Glomerulonephritis Register and a review of the literature. Nephrol Dial Transplant 1998;13 Suppl 7:12-6.CrossRefPubMedGoogle Scholar
  36. 36.
    Farrington K, Levison DA, Greenwood RN, Cattell WR, Baker LR. Renal biopsy in patients with unexplained renal impairment and normal kidney size. Q J Med 1989;70(263):221-33.PubMedGoogle Scholar
  37. 37.
    Harmark L vH, deGroot MC, vanGrootheest AC. Proton pump inhibitor induced acute interstitial nephritis. Br J Clin Pharmacol 2007; 64 (6): 819–823.PubMedGoogle Scholar
  38. 38.
    Spanou Z, Keller M, Britschgi M, et al. Involvement of drug-specific T cells in acute drug-induced interstitial nephritis. J Am Soc Nephrol 2006;17(10):2919-27.CrossRefPubMedGoogle Scholar
  39. 39.
    Crane IJ, Forrester JV. Th1 and Th2 lymphocytes in autoimmune disease. Crit Rev Immunol 2005;25(2):75–102.CrossRefPubMedGoogle Scholar
  40. 40.
    Pichler WJ. Delayed drug hypersensitivity reactions. Ann Intern Med 2003;139(8):683-93.PubMedGoogle Scholar
  41. 41.
    Pichler WJ, Beeler A, Keller M, et al. Pharmacological interaction of drugs with immune receptors: the p-i concept. Allergol Int 2006;55(1):17–25.CrossRefPubMedGoogle Scholar
  42. 42.
    Rossert J. Drug-induced acute interstitial nephritis. Kidney Int 2001;60(2):804–17.CrossRefPubMedGoogle Scholar
  43. 43.
    Wilson CB. Study of the immunopathogenesis of tubulointerstitial nephritis using model systems. Kidney Int 1989;35(4):93853.CrossRefGoogle Scholar
  44. 44.
    Pusey CD, Saltissi D, Bloodworth L, Rainford DJ, Christie JL. Drug associated acute interstitial nephritis: clinical and pathological features and the response to high dose steroid therapy. Q J Med 1983;52(206):194–211.PubMedGoogle Scholar
  45. 45.
    Preddie DC MG, Radhakrishnan J, Nickolas TL, D’Agati VD, Schwimmer JA, Gardenswartz M, Rosen R, Appel GB. Mycophenolate Mofetil for the Treatment of Interstitial Nephritis. Clin J Am Soc Nephro 2006;11:718-22.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Ursula C. Brewster
    • 1
  • Mark A. Perazella
    • 1
  1. 1.Section of NephrologyYale University School of MedicineNew HavenUSA

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