Drug-induced Acute Interstitial Nephritis: Pathology, Pathogenesis, and Treatment

Authors

  • Namrata Krishnan Section of Nephrology, Yale University School of Medicine and VAMC, New Haven, Connecticut, USA Author
  • Mark A Perazella Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut, USA Author

Abstract

Drug-induced acute interstitial nephritis (DAIN) is a common cause of acute kidney injury and often presents as an unexplained rise in serum creatinine level. Kidney biopsy is therefore frequently required to make a definitive diagnosis. The hallmark pathologic features of DAIN are interstitial edema, interstitial inflammation, and tubulitis with a predominance of CD4+ T lymphocytes and mononuclear cells, with variable numbers of eosinophils. This is a result of a type B idiosyncratic non-immunoglobulin-E-mediated immune reaction marked by cell-mediated immune injury to the renal tubulointerstitium. The drug becomes immunogenic via various mechanisms such as haptenization, antigen mimicry, and neo-antigen formation. Renal interstitial dendritic cells, and renal tubular epithelial cells play an important role in further propagating this immunologic injury. Acute DAIN can progress within days to weeks to a chronic form triggered by fibroblast activation and manifested as interstitial fibrosis and tubular atrophy. The mainstay of treatment of DAIN is discontinuation of the offending drug. Incomplete renal recovery is seen in one-third of the patients and depends on the duration of injury prior to diagnosis. Use of steroids for treatment of DAIN makes biological sense, but lack of randomized controlled trials and conflicting data from retrospective studies makes the approach unclear. Positive effects include faster recovery of kidney function, more complete recovery with less chronic kidney disease, and reduced need for chronic dialysis. Therefore, it seems reasonable to employ corticosteroids in patients that do not rapidly improve 3 to 5 days following discontinuation of the offending agent.

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Author Biographies

  • Namrata Krishnan, Section of Nephrology, Yale University School of Medicine and VAMC, New Haven, Connecticut, USA

    Assistant Professor of Medicine

    Department of Medicine/Section of Nephrology

  • Mark A Perazella, Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut, USA

    Professor of Medicine

    Department of Medicine/Section of Nephrology

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Published

2015-01-20

Issue

Section

REVIEW | Kidney Diseases

How to Cite

Drug-induced Acute Interstitial Nephritis: Pathology, Pathogenesis, and Treatment. (2015). Iranian Journal of Kidney Diseases, 9(1), 3-13. https://ijkd.org/index.php/ijkd/article/view/1982