Journal of Nephrology

, Volume 29, Issue 5, pp 611–616 | Cite as

PPIs and kidney disease: from AIN to CKD

  • Dennis G. Moledina
  • Mark A. PerazellaEmail author


Proton pump inhibitors (PPIs) are commonly prescribed and available over-the-counter, and are taken by millions of patients around the world, often for many months to years. While PPIs have an excellent overall safety profile, concerns have been raised about adverse renal events, specifically their association with acute interstitial nephritis (AIN). While only a small proportion of patients develop AIN from PPIs, these drugs are now a common cause of drug-induced AIN in the developed world due to their widespread and prolonged use. PPI-induced AIN is often subtle and without systemic allergic manifestations; subclinical, leading to gradually progressive kidney failure; delayed, median time from drug initiation to AIN diagnosis often exceeds 6 months; and often unsuspected prior to a biopsy. While the association between PPIs and AIN is well described, the population incidence of PPI-induced AIN and its contribution to the burden of chronic kidney disease (CKD) was unclear, until recently. First, two population-based studies described higher risk of AIN and acute kidney injury in patients prescribed PPIs. Second, evidence suggests that on intermediate to longer term follow-up, patients have a lower estimated glomerular filtration rate after an episode of PPI-induced AIN and patients prescribed PPIs have higher CKD risk.


Proton pump inhibitors Acute interstitial nephritis Chronic kidney disease 


Compliance with ethical standards

Conflict of interest

There are no potential conflicts of interest for the authors.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. 1.
    Forgacs I, Loganayagam A (2008) Overprescribing proton pump inhibitors. BMJ 336:2–3CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Brewster UC, Perazella MA (2007) Proton pump inhibitors and the kidney: critical review. Clin Nephrol 68(2):65–72CrossRefPubMedGoogle Scholar
  3. 3.
    Howden CWRJ (1984) Omeprazole, a gastric ‘proton pump inhibitor’: lack of effect on renal handling of electrolytes and urinary acidification. Eur J Clin Pharmacol 26:639–640CrossRefPubMedGoogle Scholar
  4. 4.
    Sanborn K (ed) (2007) Physicians desk reference, 61st edn. Thomson PDR, MontvaleGoogle Scholar
  5. 5.
    Ishizaki T, Horai Y (1999) Review article: cytochrome P450 and the metabolism of proton pump inhibitors–emphasis on rabeprazole. Aliment Pharmacol Ther 13(Suppl 3):27–36CrossRefPubMedGoogle Scholar
  6. 6.
    Ruffenach SJ, Siskind MS, Lien YH (1992) Acute interstitial nephritis due to omeprazole. Am J Med 93(4):472–473CrossRefPubMedGoogle Scholar
  7. 7.
    Post ATVG, Zanen AL (2000) Reversible renal failure after treatment with omeprazole. Neth J Med 57:58–61CrossRefPubMedGoogle Scholar
  8. 8.
    Myers RP, McLaughlin K, Hollomby DJ (2001) Acute interstitial nephritis due to omeprazole. Am J Gastroenterol 96(12):3428–3431CrossRefPubMedGoogle Scholar
  9. 9.
    Portera-Cailliau CSA (1999) Acute interstitial nephritis due to omeprazole. Ann Long Term Care 7(5):206–207Google Scholar
  10. 10.
    Wall CA, Gaffney EF, Mellotte GJ (2000) Hypercalcaemia and acute interstitial nephritis associated with omeprazole therapy. Nephrol Dial Transplant 15(9):1450–1452CrossRefPubMedGoogle Scholar
  11. 11.
    Geetha D (1999) Omeprazole-induced acute interstitial nephritis. Am J Gastroenterol 94(11):3375–3376CrossRefPubMedGoogle Scholar
  12. 12.
    Torregrosa E, Rovira RE, Calvo C, Hernandez-Jaras J, Maduell F, Garcia H (2004) Acute interstitial nephritis associated with omeprazole therapy. Nefrologia 24(Suppl 3):61–63PubMedGoogle Scholar
  13. 13.
    Torpey N, Barker T, Ross C (2004) Drug-induced tubulo-interstitial nephritis secondary to proton pump inhibitors: experience from a single UK renal unit. Nephrol Dial Transplant 19(6):1441–1446CrossRefPubMedGoogle Scholar
  14. 14.
    Simpson IJMM, Pilmore H, Manley P, Williams L, Thein H, Voss D (2006) Proton Pump Inhibitor and acute interstitial nephritis: report and analysis of 15 cases. Nephrology 11:381–385CrossRefPubMedGoogle Scholar
  15. 15.
    Geevasinga N, Coleman PL, Roger SD (2005) Rabeprazole-induced acute interstitial nephritis. Nephrology (Carlton) 10(1):7–9CrossRefGoogle Scholar
  16. 16.
    Geevasinga N, Coleman PL, Webster AC, Roger SD (2006) Proton pump inhibitors and acute interstitial nephritis. Clin Gastroenterol Hepatol 4(5):597–604CrossRefPubMedGoogle Scholar
  17. 17.
    Christensen PB, Albertsen KE, Jensen P (1993) Renal failure after omeprazole. Lancet 341(8836):55CrossRefPubMedGoogle Scholar
  18. 18.
    Assouad M, Vicks SL, Pokroy MV, Willcourt RJ (1994) Recurrent acute interstitial nephritis on rechallenge with omeprazole. Lancet 344(8921):549CrossRefPubMedGoogle Scholar
  19. 19.
    Gronich JHSE, Stein HD, Sirota RA, Yudis M (1994) Omeprazole related acute interstitial nephritis (AIN) with omeprazole (Abstract). JASN 5:394Google Scholar
  20. 20.
    Brewster UC, Perazella MA (2007) Acute kidney injury following proton pump inhibitor therapy. Kidney Int 71(6):589–593CrossRefPubMedGoogle Scholar
  21. 21.
    Ra A, Tobe SW (2004) Acute interstitial nephritis due to pantoprazole. Ann Pharmacother 38(1):41–45CrossRefPubMedGoogle Scholar
  22. 22.
    Buysen JG, Houthoff HJ, Krediet RT, Arisz L (1990) Acute interstitial nephritis: a clinical and morphological study in 27 patients. Nephrol Dial Transplant 5(2):94–99CrossRefPubMedGoogle Scholar
  23. 23.
    Clarkson MR, Giblin L, O’Connell FP et al (2004) Acute interstitial nephritis: clinical features and response to corticosteroid therapy. Nephrol Dial Transplant 19(11):2778–2783CrossRefPubMedGoogle Scholar
  24. 24.
    Davison AM, Jones CH (1998) Acute interstitial nephritis in the elderly: a report from the UK MRC Glomerulonephritis Register and a review of the literature. Nephrol Dial Transplant 13(Suppl 7):12–16CrossRefPubMedGoogle Scholar
  25. 25.
    Perazella MA, Markowitz GS (2010) Drug-induced acute interstitial nephritis. Nat Rev Nephrol 6(8):461–470CrossRefPubMedGoogle Scholar
  26. 26.
    Harmark L, van der Wiel HE, deGroot MC, vanGrootheest AC (2007) Proton pump inhibitor induced acute interstitial nephritis. Br J Clin Pharmacol 64(6):819–823PubMedPubMedCentralGoogle Scholar
  27. 27.
    Muriithi AK, Leung N, Valeri AM, Cornell LD, Sethi S, Fidler ME, Nasr SH (2014) Biopsy-proven acute interstitial nephritis, 1993–2011: a case series. Am J Kidney Dis 64(4):558–566CrossRefPubMedGoogle Scholar
  28. 28.
    Blank ML, Parkin L, Paul C, Herbison P (2014) A nationwide nested case–control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use. Kidney Int 86(4):837–844CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Antoniou T, Macdonald EM, Hollands S, Gomes T, Mamdani MM, Garg AX, Paterson JM, Juurlink DN (2015) Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study. CMAJ 3(2):E166–E171CrossRefGoogle Scholar
  30. 30.
    Lazarus B, Chen Y, Wilson FP, Sang Y, Chang AR, Coresh J, Grams ME (2016) Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med 176:238–246CrossRefPubMedGoogle Scholar
  31. 31.
    Arora P, Golzy M, Gupta A, Ranjan R, Carter R, Lohr J (2015) Proton pump inhibitors are associated with increased risk of development of chronic kidney disease [Abstract]. J Am Soc Nephrol 26:219AGoogle Scholar

Copyright information

© Italian Society of Nephrology 2016

Authors and Affiliations

  1. 1.Section of NephrologyYale University School of MedicineNew HavenUSA
  2. 2.VA Medical CenterWest HavenUSA

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