Process of tubulointerstitial injury in progressive renal diseases

Abstract

The constant findings of tubulointerstitial injury in a variety of progressive glomerulopathies raise the possibility that the derangement of glomerular structure may instigate tubulointserstitial injury. The secondary processes in tubulointerstitial injury as a response to glomerular injury may be related to filtered plasma proteins and nephron loss. The increased permeability allows plasma proteins such as albumin, complement components, transterrin and lipoproteins, to leak into the urinary space and access the tubule, which may be instrumental in the development of renal fibrosis. The nephron loss resulting from progressive glomerular diseases may induce hypermetabolism and hypertrophy in the surviving nephrons, which may be responsible for progressive tubulointerstitial injury. Tubular cells stressed by heavy proteinuria, hypermetabolism, or hypertrophy are thought to transdifferentiate into fibroblastic cells and begin to express cytokines, adhesion molecules, and proteases. Such factors involved in tubulointerstitial fibrosis may be candidates for therapeutic targets. A variety of cytokine inhibitors, as well as gene transfer into tubulus and interstitium, have been examined as possible cardidates for the therapy of tubulointerstitial fibrosis. Transforming growth factor-β (TGF-β) soluble receptor and retrogade transfection of the TGF-β antisense gene have been reported to be effective for prevention of tubulointerstitial fibrosis.