The Pathogenesis of Tubulointerstitial Nephritis

Tubulointerstitial nephritis is a common form of both acute and chronic renal disease in humans. Over the last 12 years we have been studying the pathogenic mechanisms involved in tubulointerstitial nephritis, using several animal models which are similar to distinct forms of human interstitial injury. The immunopathogenesis of tubulointerstitial nephritis can be arbitrarily divided into three phases. The afferent, or antigen recognition phase, involves expression of the nephritogenic antigen, recognition and presentation of the nephritogenic antigen in the context of appropriate MHC determinants, and circumvention of the usual mechanisms of tolerance. The immunoregulatory phase consists of multiple counter-regulatory events, both humoral and cell-mediated, that influence the amplitude and qualitative nature of the immune response. The final, effector, phase includes the various mechanisms directly responsible for tubulointerstitial injury and subsequent fibrosis. Additionally, once the immune response has been initiated, a number of factors can influence the progression of tubulointerstitial injury toward end stage renal disease.