Pathophysiology of acute interstitial nephritis

Abstract

Acute interstitial nephritis (AIN) is an important ‘renal’ cause of acute kidney injury, though less common than, acute tubular necrosis and acute glomerulonephritis. Interstitial inflammation is also seen in glomerular diseases, but is not considered as AIN, possibly because of different pathophysiology. Two-thirds of cases of AIN are due to drugs like NSAIDs and antimicrobials. The presentation of AIN is with non-specific symptoms and signs, with <10% patients having systemic features of immune reaction like fever, rashes, arthralgias, and eosinophilia. Most of the cases of AIN are diagnosed clinically. Biopsy, when available, shows interstitial edema and infiltrates of lymphocytes, macrophages, eosinophils, plasma cells, and neutrophils. The glomeruli are typically normal. Presence of large number of T cells in biopsy specimen confirms cell mediated immune pathomechanism as a major cause of injury. Withdrawal of offending drug may lead to recovery or may require steroid treatment to expedite the recovery phase. Delayed treatment of AIN may lead to irreversible damage in the form of interstitial fibrosis and chronic interstitial nephritis. The patho-mechanism of irreversible damage is also complex involving ‘epithelial-mesenchymal transition’, whereby tubular cells possibly, by virtue of growth factors, become fibroblast like cells.