الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Renal fibrosis is a non-specific process, representing the final common pathway for all kidney diseases, irrespective of their initial cause (infectious, autoimmune, toxic or obstructive), histological injury (glomerular, vascular, tubular or interstitial) or etiology (congenital or acquired), leading to gradual expansion of the fibrotic mass which destroys the normal structure of the tissue and results in organ dysfunction (chronic kidney disease or CKD) and, ultimately, in end-stage organ failure (end stage renal disease or ESRD).
Although a range of diseases such as glomerulonephritis; metabolic diseases, including diabetes mellitus and atherosclerosis; obstructive nephropathy; interstitial nephritis; and cystic nephropathies, including polycystic kidney disease, can be the major causes of CKD, renal fibrosis is always the common ultimate result of CKD.
Renal fibrosis is a key determinant of the progression of many renal diseases and represents a final common pathway that adversely affects outcome. The evolution of renal fibrosis is complicated and involves many cellular and molecular mediators.
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. 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 .
(iv) Epithelial-to-mesenchymal transition (EMT) of TECs.
Many promising targets for the treatment of renal fibrosis have been validated in various animal models, and even more new targets have been identified. For several of the targets reviewed, substances/drugs have already been developed, are being tested, or are already being therapeutically employed in patients with non-renal indications.
Renal fibrosis, in contrast, remains a largely uncharted territory in clinical trials. The reasons for this are certainly multifactorial and may include long study durations if hard endpoints, i.e. loss of GFR, are to be aimed for and, in particular, the lack of non-invasive markers or diagnostic tools to assess kidney scarring, and thus, monitor therapy. However, the industry has noted the enormous potential market, given the possibility of developing antifibrotic therapy that might be of benefit in many different types of organ fibrosis. Furthermore, there is hope that with a large consortia search for biomarkers and advancing ultrasound, or through MR-based or molecular-imaging techniques, even monitoring of the disease process may become feasible in the near future.
In the past years, many promising targets for the treatment of renal fibrosis have been validated in various animal models, and even more new targets have been identified. For several of the targets reviewed, substances/drugs have already been developed, are being tested, or are already being therapeutically employed in patients with non-renal indications.