Treatment targets in renal fibrosis

作者：Peter Boor, Katarı́na Šebeková, Tammo Ostendorf, Jürgen Floege · 发表于：Nephrology Dialysis Transplantation · 年份：2007 · DOI：10.1093/ndt/gfm393 · 被引用次数：154 · 研究领域：Chronic Kidney Disease and Diabetes、Renal Diseases and Glomerulopathies、Muscle and Compartmental Disorders

Renal fibrosis is the principal process underlying the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). It is a relatively uniform response involving glomerulosclerosis, tubulointerstitial fibrosis and changes in renal vasculature (loss of glomerular and peritubular capillaries) ( Figure 1 ). Of these, tubulointerstitial fibrosis has evolved as the most consistent predictor of an irreversible loss of renal function and progression to ESRD [ 1 ]. ... Mechanisms contributing to tubulointerstitial injury and tubular atrophy include glomerular proteinuria, chronic hypoxia, misdirected glomerular ultrafiltration, tubular protein leakage and direct toxic insults of e.g. drugs (reviewed in detail elsewhere [ 1–6 ]). Direct or indirect tubulointerstitial injury via oxidative stress and various effector molecules trigger cellular responses like (i) tubular epithelial cell (TEC) apoptosis, (ii) activation of fibroblasts and their phenotypic switch to myofibroblasts, (iii) influx and/or proliferation of lymphocytes/macrophages, fibrocytes (the circulating fibroblast precursors), fibroblasts as well as (iv) epithelial-to-mesenchymal transition (EMT) of TECs.