Medication-Induced Interstitial Nephritis in the 21st Century

Interstitial nephritis is an immune mediated form of tubulointerstitial kidney injury that may occur secondary to drugs, autoimmune disease, infections, and hematologic disorders or as a reactive process. Drug-induced acute interstitial nephritis (DI-AIN) occurs in 0.5%-3% of all kidney biopsies and in 5%-27% of biopsies performed for acute kidney injury. Drugs are implicated in 70%-90% of biopsy-proved IN with a prevalence of 50% in less developed to 78% in more developed countries. DI-AIN typically is idiosyncratic because of a delayed hypersensitivity reaction, although some chemotherapeutic agents are permissive for immune upregulation and injure the kidney in a dose-related manner. Antibiotics are the most implicated class of medication in DI-AIN, followed by proton pump inhibitors, nonsteroidal anti-inflammatory agents, and 5-aminosalicylates. Diuretics, allopurinol, phenytoin and other anti-seizure medications, and H2 receptor antagonists are known offenders while chemotherapeutic agents are an under-recognized cause. The symptoms of DI-AIN are variable and often not specific; thus, kidney biopsy is required to make a firm diagnosis. The incidence of DI-AIN appears to be increasing, particularly in the elderly in whom kidney biopsy is underused, and identification of the offending agent may be complicated by polypharmacy. As rapid drug discontinuation may improve prognosis, the possibility of DI-AIN should always be considered in a patient with acute kidney injury.