Interstitial Pathomechanisms Underlying Progressive Tubulointerstitial Damage

Progressive renal disease poses an increasing problem for the medical community. Though the causes of end-stage renal failure are multiple, the histologic pictures of chronic renal disease are remarkably similar being characterized by interstitial infiltration, fibrosis, tubular atrophy and dilatation. This similarity points to a final common pathway. In addition, renal disease often progresses despite elimination or amelioration of the inciting stimulus. This review deals with the pathomechanisms of progressive renal failure proposing a three-step model of fibrogenesis with an induction phase, a phase of inflammatory, and, lastly, a phase of postinflammatory matrix synthesis. The central role of the tubular epithelial cell as a mediator of interstitial inflammation and its participation in matrix synthesis will be discussed particularly. Finally, a brief overview is listed on new therapeutic approaches to limit the progressive nature of fibrogenesis.