THE PATHOGENESIS OF TUBULOINTERSTITIAL DISEASE-ASSOCIATED WITH GLOMERULONEPHRITIS - THE GLOMERULAR CYTOKINE THEORY

Numerous studies have suggested that tubulointerstitial disease has a major impact on the overall function and prognosis of glomerular disea se. The mechanism by which tubulointerstitial disease develops in pati ents with glomerular and other diseases is unknown. In this review, we discuss the hypothesis that factors released from injured glomeruli a ct on tubules and interstitial cells to induce expression of chemotact ic and adhesive factors that attract mononuclear cells into the inters titium. Evidence is provided that osteopontin is one candidate leukocy te adhesive factor involved in this process, but others are likely inv olved. The recruited leukocytes (primarily macrophages) then release i nflammatory mediators that injure tubular cells and activate interstit ial fibroblasts, resulting in tubulointerstitial injury with eventual fibrosis.