Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Drug-induced acute interstitial nephritis

Nature Reviews Nephrology volume 6, pages 461–470 (2010)Cite this article

Subjects

Abstract

Acute interstitial nephritis (AIN) is a common cause of acute kidney injury. Many etiologies of AIN have been recognized—including allergic/drug-induced, infectious, autoimmune/systemic, and idiopathic forms of disease. The most common etiology of AIN is drug-induced disease, which is thought to underlie 60–70% of cases. Multiple agents from many different classes of drugs can cause AIN, and the clinical presentation and laboratory findings vary according to the class of drug involved. AIN is characterized by interstitial inflammation, tubulitis, edema, and in some cases, eventual interstitial fibrosis. A definitive diagnosis of AIN can be established only by kidney biopsy. Noninvasive tests such as 67gallium scintigraphy and testing for eosinophiluria have limited diagnostic utility. The mainstay of therapy for drug-induced AIN is timely discontinuation of the causative agent. Although the benefits of corticosteroid therapy remain unproven, they do appear to have a positive effect in some patients with drug-induced AIN, especially when treatment is initiated early in the course of the disease. In general, the prognosis for drug-induced AIN is good, and at least partial recovery of kidney function is normally observed. Early recognition is crucial because patients can ultimately develop chronic kidney disease.

Key Points

  • Acute interstitial nephritis (AIN), which is primarily drug-induced, is a relatively common cause of acute kidney injury

  • The clinical presentation of AIN varies with the class of drug involved

  • A definitive diagnosis of AIN requires kidney biopsy because noninvasive laboratory tests and imaging studies lack sensitivity and specificity

  • Pathological findings in drug-induced AIN include interstitial inflammation, tubulitis, edema, and in some cases interstitial fibrosis

  • Corticosteroids may be beneficial to treat drug-induced AIN, especially when administered early in the course of disease

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: White blood cell cast in the urine of a patient with acute interstitial nephritis.
Figure 2: The hallmarks of acute interstitial nephritis.

Similar content being viewed by others

References

  1. Councilman, W. T. Acute interstitial nephritis. J. Exp. Med. 3, 393–420 (1898).

    Article  CAS  Google Scholar 

  2. Cornell, L. D. et al. Pseudotumors due to IgG4 immune-complex tubulointerstitial nephritis associated with autoimmune pancreatocentric disease. Am. J. Surg. Path. 31, 1586–1597 (2007).

    Article  Google Scholar 

  3. Baldwin, D. S., Levine, B. B., McCluskey, R. T. & Gallo, G. R. Renal failure and interstitial nephritis due to penicillin and methicillin. N. Engl. J. Med. 279, 1245–1252 (1968).

    Article  CAS  Google Scholar 

  4. Buysen, J. G., Houtlhoff, H. J., Krediet, R. T. & Arisz, L. Acute interstitial nephritis:a clinical and morphological study in 27 patients. Nephrol. Dial. Transplant. 5, 94–99 (1990).

    Article  CAS  Google Scholar 

  5. Davison, A. M. & Jones, C. H. Acute interstitial nephritis in the elderly: A report from the UK MDC Glomerulonephritis Register and a review of the literature. Nephrol. Dial. Transplant. 13 (Suppl. 7), 12–16 (1998).

    Article  Google Scholar 

  6. Clarkson, M. R. et al. Acute interstitial nephritis: clinical features and response to corticosteroid therapy. Nephrol. Dial. Transplant. 19, 2778–2783 (2004).

    Article  CAS  Google Scholar 

  7. Farrington, K., Levison, D. A., Greenwood, R. N., Cattell, W. R. & Baker, L. R. Renal biopsy in patients with unexplained renal impairment and normal kidney size. Q. J. Med. 70, 221–233 (1989).

    CAS  PubMed  Google Scholar 

  8. Baker, R. J. & Pusey, C. D. The changing profile of acute tubulointerstitial nephritis. Nephrol. Dial. Transplant. 19, 8–11 (2004).

    Article  Google Scholar 

  9. Bijol, V., Mendez, G. P., Nose, V. & Rennke, H. G. Granulomatous interstitial nephritis: a clinicopathologic study of 46 cases from a single institution. Int. J. Surg. Pathol. 14, 57–63 (2006).

    Article  Google Scholar 

  10. Michel, D. M. & Kelly, C. J. Acute interstitial nephritis. J. Am. Soc. Nephrol. 9, 506–515 (1998).

    CAS  PubMed  Google Scholar 

  11. Kodner, C. M. & Kudrimoti, A. Diagnosis and management of acute interstitial nephritis. Am. Fam. Physician 67, 2527–2534 (2003).

    PubMed  Google Scholar 

  12. Alexopoulos, E. Drug-induced acute interstitial nephritis. Ren. Fail. 20, 809–819 (1998).

    Article  CAS  Google Scholar 

  13. Rossert, J. Drug-induced acute interstitial nephritis. Kidney Int. 60, 804–817 (2001).

    Article  CAS  Google Scholar 

  14. Bhaumik, S. K. et al. Evaluation of clinical and histological prognostic markers in drug-induced acute interstitial nephritis. Ren. Fail. 18, 97–104 (1996).

    Article  CAS  Google Scholar 

  15. Ooi, B. S., Jao, W., First, M. R., Mancilla, R. & Pollak, V. E. Acute interstitial nephritis. Am. J. Med. 59, 614–629 (1975).

    Article  CAS  Google Scholar 

  16. Toto, R. D. Acute tubulointerstitial nephritis. Am. J. Med. Sci. 299, 392–410 (1990).

    Article  CAS  Google Scholar 

  17. Mills, R. M. Severe hypersensitivity reactions associated with allopurinol. JAMA 216, 799–802 (1971).

    Article  Google Scholar 

  18. Simenhoff, M. L., Guild, W. R. & Dammin, G. J. Acute diffuse intersitial nephritis: review of the literature and case report. Am. J. Med. 44, 618–625 (1968).

    Article  CAS  Google Scholar 

  19. Baker, S. B. & Williams, R. T. Acute interstitial nephritis due to drug sensitivity. Br. Med. J. 1, 1655–1658 (1963).

    CAS  PubMed  Google Scholar 

  20. Corwin, H. L., Korbet, S. M. & Schwartz, M. M. Clinical correlates of eosinophiluria. Arch. Intern. Med. 145, 1097–1099 (1985).

    Article  CAS  Google Scholar 

  21. Ditlove, J., Weidmann, P., Bernstein, M. & Massry, S. G. Methicillin nephritis. Medicine (Baltimore) 56, 483–491 (1977).

    Article  CAS  Google Scholar 

  22. Linton, A. L., Clark, W. F., Driedger, A. A., Turnbull, I. & Lindsay, R. M. Acute interstitial nephritis due to drugs. Ann. Intern. Med. 93, 735–741 (1980).

    Article  CAS  Google Scholar 

  23. Nolan, C. R., Anger, M. S. & Kelleher, S. P. Eosinophiluria: a new detection and definition of the clinical spectrum. N. Engl. J. Med. 315, 1516–1519 (1986).

    Article  Google Scholar 

  24. Corwin, H. L., Bray, R. A. & Haber, M. H. The detection and interpretation of urinary eosinophils. Arch. Pathol. Lab. Med. 113, 1256–1258 (1989).

    CAS  PubMed  Google Scholar 

  25. Ruffing, K. A. et al. Eosinophils in urine revisited. Clin. Nephrol. 41, 163–166 (1994).

    CAS  PubMed  Google Scholar 

  26. Koselj, M., Kveder, R., Bren, A. F. & Rott, T. Acute renal failure in patients with drug-induced acute interstitial nephritis. Ren. Fail. 15, 69–72 (1993).

    Article  CAS  Google Scholar 

  27. D'Agati, V. D., Theise, N. D., Pirani, C. L., Knowles, D. M. & Appel, G. B. Interstitial nephritis related to nonsteroidal anti-inflammatory agents and β-lactam antibiotics: a comparative study of the interstitial infiltrates using monoclonal antibodies. Modern Pathol. 2, 390–396 (1989).

    CAS  Google Scholar 

  28. Border, W. A. et al. Antitubular basement-membrane antibodies in methicillin-associated interstitial nephritis. N. Engl. J. Med. 291, 381–384 (1974).

    Article  CAS  Google Scholar 

  29. Pirani, C. L., Valeri, A., D'Agati, V. & Appel, G. B. Renal toxicity of nonsteroidal anti-inflammatory drugs. Contr. Nephrol. 55, 159–175 (1987).

    Article  CAS  Google Scholar 

  30. Campese, V. M., Marzullo, F., Schena, F. P. & Coratelli, P. Acute renal failure during intermittent rifampicin therapy. Nephron 10, 256–261 (1973).

    Article  CAS  Google Scholar 

  31. Kleinknecht, D. et al. Acute interstitial nephritis due to drug hypersensitivity. An up-to-date review with a report of 19 cases. Adv. Nephrol. Necker Hosp. 12, 277–308 (1983).

    CAS  PubMed  Google Scholar 

  32. Perazella, M. A. Acute renal failure in HIV-infected patients: a brief review of common causes. Am. J. Med. Sci. 319, 385–391 (2000).

    Article  CAS  Google Scholar 

  33. Perazella, M. A. Drug-induced renal failure: update on new medications and unique mechanisms of nephrotoxicity. Am. J. Med. Sci. 325, 349–362 (2003).

    Article  Google Scholar 

  34. Perazella, M. A. & Tray, K. Selective cyclooxygenase-2 inhibitors: a pattern of nephrotoxicity similar to traditional nonsteroidal anti-inflammatory drugs. Am. J. Med. 111, 64–67 (2001).

    Article  CAS  Google Scholar 

  35. Schwarz, A., Krause, P. H., Keller, F., Offermann, G. & Mihatsch, M. J. Granulomatous interstitial nephritis after nonsteroidal anti-inflammatory drugs. Am. J. Nephrol. 8, 410–416 (1988).

    Article  CAS  Google Scholar 

  36. Dixit, M. P. et al. Non-steroidal anti-inflammatory drug-associated acute interstitial nephritis with granular tubular basement membrane deposits. Pediatr. Nephrol. 23, 145–148 (2008).

    Article  Google Scholar 

  37. Szalat, A. et al. Acute renal failure and interstitial nephritis in a patient treated with rofecoxib: case report and review of the literature. Arthritis Rheum. 51, 670–673 (2004).

    Article  Google Scholar 

  38. Esteve, J. B., Launay-Vacher, V., Brocherious, I., Grimaldi, A. & Izzedine, H. COX-2 inhibitors and acute interstitial nephritis: Case report and review of the literature. Clin. Nephrol. 63, 385–389 (2005).

    Article  CAS  Google Scholar 

  39. Alper, A. B., Meleg-Smith, S. & Krane, N. K. Nephrotic syndrome and interstitial nephritis associated with celecoxib. Am. J. Kidney Dis. 40, 1086–1090 (2002).

    Article  Google Scholar 

  40. Markowitz, G. S. et al. Membranous glomerulopathy and acute interstitial nephritis following treatment with celecoxib. Clin. Nephrol. 59, 137–142 (2003).

    Article  CAS  Google Scholar 

  41. Brewster, U. C. & Perazella, M. A. Proton pump inhibitors and the kidney: critical review. Clin. Nephrol. 68, 65–72 (2007).

    Article  CAS  Google Scholar 

  42. Ruffenach, S. J., Siskind, M. S. & Lien, Y. H. Acute interstitial nephritis due to omeprazole. Am. J. Med. 93, 472–473 (1992).

    Article  CAS  Google Scholar 

  43. Geevasinga, N., Coleman, P. L., Webster, A. C. & Roger, S. D. Proton pump inhibitors and acute interstitial nephritis. Clin. Gastroenterol. Hepatol. 4, 597–604 (2006).

    Article  CAS  Google Scholar 

  44. Kuzell, W. C. & Gardner, G. M. Salicylazosulfapyridine (salazopyrin or azopyrin) in rheumatoid arthritis and experimental polyarthritis. Calif. Med. 73, 476–480 (1950).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Moss, A. C. & Peppercorn, M. A. The risks and the benefits of mesalazine as a treatment for ulcerative colitis. Expert Opin. Drug Saf. 6, 99–107 (2007).

    Article  CAS  Google Scholar 

  46. World, M. J., Stevens, P. E., Ashton, M. A. & Rainford, D. J. Mesalamine-associated interstitial nephritis. Nephrol. Dial. Transplant. 11, 614–621 (1996).

    Article  CAS  Google Scholar 

  47. Arend, L. J. & Springate, J. E. Interstitial nephritis from mesalamine: case report and literature review. Pediatr. Nephrol. 19, 550–553 (2004).

    Article  Google Scholar 

  48. Gisbert, J. P., González-Lama, Y. & Maté, J. 5-Aminosalicylates and renal function in inflammatory bowel disease: a systemic review. Inflamm. Bowel Dis. 13, 629–638 (2007).

    Article  Google Scholar 

  49. Elseviers, M. M. et al. Renal impairment in patients with inflammatory bowel disease: Association with aminosalicylate therapy? Clin. Nephrol. 61, 83–89 (2004).

    Article  CAS  Google Scholar 

  50. Corrigan, G. & Stevens, P. E. Interstitial nephritis associated with the use of mesalazine in inflammatory bowel disease. Aliment. Pharmacol. Ther. 14, 1–6 (2000).

    Article  CAS  Google Scholar 

  51. Hiroaka, M. et al. Ultrasonographic findings of acute interstitial nephritis. Am. J. Nephrol. 16, 154–158 (1996).

    Article  Google Scholar 

  52. Linton, A. L. et al. 67Gallium scintigraphy in the diagnosis of acute renal disease. Clin. Nephrol. 24, 84–87 (1985).

    CAS  PubMed  Google Scholar 

  53. Graham, G. D., Lundy, M. M. & Moreno, J. J. Failure of 67Gallium scintigraphy to identify reliably non-infectious interstitial nephritis. J. Nucl. Med. 24, 568–570 (1983).

    CAS  PubMed  Google Scholar 

  54. Laberke, H. G. & Bohle, A. Acute interstitial nephritis: correlations between clinical and morphological findings. Clin. Nephrol. 14, 263–273 (1980).

    CAS  PubMed  Google Scholar 

  55. Pusey, C. D. et al. Drug associated acute interstitial nephritis: clinical and pathological features and the response to high dose steroid therapy. Q. J. Med. 52, 194–211 (1983).

    CAS  PubMed  Google Scholar 

  56. Gonzalez, E. et al. Early steroid treatment improves the recovery of renal function in patients with drug-induced acute interstitial nephritis. Kidney Int. 73, 940–946 (2008).

    Article  CAS  Google Scholar 

  57. Preddie, D. C. et al. Mycophenylate mofetil for the treatment of interstitial nephritis. Clin. J. Am. Soc. Nephrol. 1, 718–722 (2006).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank G. Fogazzi, Research Laboratory on Urine, Unità Operativa di Nefrologia, Fondazione IRCCS, Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy for his kind contribution of Figure 1 for this article.

Author information

Authors and Affiliations

  1. Section of Nephrology, Yale University School of Medicine, FMP 107, 330 Cedar Street, New Haven, 06520-8029, CT, USA

    Mark A. Perazella

  2. Department of Pathology, Columbia University Medical Center, 630 West 168 Street, VC 14-224, New York, 10032, NY, USA

    Glen S. Markowitz

Authors
  1. Mark A. Perazella
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Glen S. Markowitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Glen S. Markowitz.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Perazella, M., Markowitz, G. Drug-induced acute interstitial nephritis. Nat Rev Nephrol 6, 461–470 (2010). https://doi.org/10.1038/nrneph.2010.71

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneph.2010.71

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing