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.
Strutz
F
F
Department of Nephrology and Rheumatology, Georg-August-University Medical Center, Göttingen, Germany. fstrutz@gwdg.de
Müller
G A
GA
D000818:Animals; D018450:Disease Progression; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology* / Q000503:physiopathology* / Q000628:therapy; D007684:Kidney Tubules / Q000473:pathology*