Tubular-derived growth factors and cytokines in the pathogenesis of tubulointerstitial fibrosis: implications for human renal disease progression

Abstract

Detailed histomorphometric analysis of human biopsy tissue over the last 30 years has convincingly demonstrated that preservation of the tubulointerstitial compartment of the kidney is the major determinant of renal outcome in a variety of human renal diseases. Nevertheless, the pathophysiology of tubulointerstitial disease remains obscure. In particular, the primary role of tubular injury has not been explored adequately. There is now accumulating evidence that apart from their many transport functions, tubular cells also secrete an array of cytokines, including chemotactic cytokines, polypeptide growth factors, and vasoactive peptides. Three paracrine growth systems acting at different levels in the kidney are described as examples of potential interactions between tubular and interstitial cells in health and disease. We hypothesize that while glomerular injury may precede tubular injury, it is tubular injury that sets into motion the irreversible process of tubulointerstitial fibrosis characteristic of progressive human renal disease, leading to secondary loss of glomerular function.