الفهرس 
Causes of renal fibrosisOnly 14 pages are availabe for public view
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Abstract
Renal fibrosis is the inevitable consequence of an excessive accumulation of extracellular matrix that occurs in virtually every type of chronic kidney disease.The pathogenesis of renal fibrosis is a progressive process that ultimately leads to end-stage renal failure, a devastating disorder that requires dialysis or kidney transplantation. In a simplistic view, renal fibrosis represents a failed wound-healing process of the kidney tissue after chronic, sustained injury. Several cellular pathways, including mesangial and fibroblast activation as well as tubular epithelial–mesenchymal transition, have been identified as the major avenues for the generation of the matrix-producing cells in diseased conditions.Among the many fibrogenic factors that regulate renal fibrotic process, Transforming Growth Factor- (TGF-) is one that plays a central role. Although defective matrix degradation may contribute to tissue scarring, the exact action and mechanisms of the matrix-degrading enzymes in the injured kidney have become increasingly complicated.Recent discoveries on endogenous antifibrotic factors have evolved novel strategies aimed at antagonizing the fibrogenic action of TGF-/Smad signaling. Many therapeutic interventions appear effective in animal models; however, translation of these promising results into humans in the clinical setting remains a daunting task. The process of renal fibrosis, in which multiple cellular events and molecular mediators participate and interact in concert, is enormously complicated. Despite these complexities, several important issues have recently come to light. In comparison to healthy wound healing, tubular EMT is a unique event that occurs in the fibrotic Tissue after chronic injury, which may set the injured kidney in motion to scar formation. It also becomes apparent that induction and activation of TGF-/Smad signaling are critical for initiating a fibrogenic response; and equally important is the loss of the Smad antagonists, which could render the fibrogenic signaling out of control.Finally, the identification of endogenous antifibrotic factors has provided us with unprecedented opportunities for therapeutic interventions of renal fibrosis. In view of the impressive efficacy of antifibrotic factors in attenuating experimental renal fibrosis, it is hoped that the translation of these studies into humans will result in improved therapeutics for patients with chronic renal insufficiency.Because renal fibrosis appears irrespective of the underlying disease (hypertension, diabetes, infection, inflammation of renal blood vessels and glomeruli, kidney stones, and cysts) and originating renal compartment (renal vessels, glomeruli, tubules), it is generally believed that is under the control of a common final physiopathological pathway independent of the primary cause. Thus identifying and targeting the systems participating in this pathway may lead to efficient treatments against renal fibrosis and failure regardless of the initiating pathology.Interstitial fibrosis does not show any visible symptoms at the very start and so it is very hard to detect. However, certain people are considered at high risk for interstitial fibrosis on account of their family history of the disease. Such individuals should undergo routine urine, blood and imaging tests to detect any traces of interstitial fibrosis. Periodic testing is the only means of detecting this condition in a timely fashion.The basic symptoms of renal or kidney interstitial fibrosis are the same as those of advancing kidney disease. They include changes in urination pattern with trouble urinating; swelling in the limbs; acute hair fall; extreme lethargy and fatigue; skin rash; taste changes including metallic taste in the mouth; severe nausea; dizziness; and leg pain. These symptoms are not comprehensive and there might be other symptoms depending on the stage of the condition and patient physiology.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. 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 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.