Hypersensitivity Nephropathy

Updated: Dec 01, 2015
  • Author: Micah L Thorp, DO, MPH; Chief Editor: Vecihi Batuman, MD, FASN  more...
  • Print


Acute interstitial nephritis (AIN) was brought to prominence as a pathological entity by an official who described 42 patients with interstitial nephritis in an 1898 treatise. During the preceding century, acute interstitial nephritis had primarily been reported in association with scarlet fever, but the 1898 report confirmed the disease as a separate and significant clinical entity.

Infections were the predominant etiologies of acute interstitial nephritis until the middle of the 20th century, when the widespread availability of antibiotics altered the usual course of most common infections. This change markedly decreased the prevalence of infection-related acute interstitial nephritis, but, in an ironic twist, antibiotics dramatically increased the rates of drug-associated acute interstitial nephritis.

Recently, proton pump inhibitors have been identified as an etiology of acute interstitial nephritis. One retrospective study from Australia indicates this class of drugs may be the etiology of most acute interstitial nephritis cases currently. [1]



Both humoral and cell-mediated immune reactions are implicated in the pathophysiology of acute interstitial nephritis. Drug-specific antibodies have been found in patients with rifampin-related acute interstitial nephritis. Patients with methicillin-related acute interstitial nephritis often have both a linear fluorescence along the tubular basement membrane as well as an antibody directed against a hapten bound to the tubular basement membrane.

Renal biopsy samples taken from patients reveal a diffuse or patchy inflammatory cell infiltrate under light microscopy. The infiltrate is typically composed of mixed T lymphocytes, plasma cells, eosinophils, and monocytes. The CD4-to-CD8 ratio is similar to that in blood. Glomerular lesions are generally not present. Immunofluorescence is usually unremarkable, although immunoglobulin G (IgG) or immunoglobulin M (IgM) staining of the tubular basement membrane is occasionally present. Patients who have acute interstitial nephritis due to nonsteroidal anti-inflammatory drugs (NSAIDs) typically present with features of minimal change disease, including fusion of foot processes.





Obtaining estimates of prevalence is difficult, especially because the criterion standard diagnostic test is a renal biopsy. One large study of Finnish conscripts with hematuria or proteinuria found a prevalence of only 1%. In studies of patients with acute renal failure, rates up to 10-15% have been established. Until a noninvasive means of making a reliable diagnosis is available, accurate data will probably not be available.