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What can target kidney fibrosis?

Fibrosis has been the ‘dark horse’ of kidney disease research, but recently its importance has come to the forefront, through recognition that it is a major contributor to progression of almost all forms of kidney disease. While the extent of fibrosis does not correlate well with glomerular filtration rate (GFR) measurements of organ function, it predicts future progression of disease with much greater certainty. No longer merely a bystander problem, in response to tubular, microvascular or podocyte disease, the cellular process of laying down matrix, known as ‘fibrogenesis’, has been recognized to amplify and sustain pathological responses in the functioning units of the kidney, and therefore…

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Articles of Interest

New Therapeutic Targets for Kidney Fibrosis Emerge

Study identifies key factor leading to Chronic kidney disease is a global health concern, affecting about 10 percent of the world’s population—and increasing in prevalence. A final, common pathway in chronic kidney disease is fibrosis. Just as fibrosis—or the formation of fibrous connective tissue—can cause devastating effects in the lung, liver, heart and elsewhere, fibrosis of the kidneys can ultimately lead to end-stage kidney failure. In recent years, investigators have found that after acute kidney injury, the kidneys often fail to completely repair themselves, and kidney cells may get stuck during the cell cycle in a state in which they release profibrotic factors. cell cycle arrest and a cellular structure that is key for kidney fibrosis progression.

Diagnosis and assessment of renal fibrosis: the state of the art

Evaluation of interstitial fibrosis is crucial to the assessment of prognosis and to guide therapy for most kidney diseases. However, how best to measure kidney fibrosis remains uncertain. Therefore, new approaches that allow a more accurate and reproducible assessment of renal interstitial fibrosis are required.

Fibrosis in Chronic Kidney Disease: Pathogenesis and Consequences

Fibrosis is a process characterized by an excessive accumulation of the extracellular matrix as a response to different types of tissue injuries, which leads to organ dysfunction. The process can be initiated by multiple and different stimuli and pathogenic factors which trigger the cascade of reparation converging in molecular signals responsible of initiating and driving fibrosis.

Fibrosis in the kidney: is a problem shared a problem halved?

However, while renal fibrosis shares many features in common with the wound healing response in other organs, we also recognise that the consequences can be highly kidney specific. This review highlights the similarities and differences between this process in the kidney and other organs, and considers the therapeutic implications.

From Proteinuria to Fibrosis: An Update on Pathophysiology and Treatment Options

This review provides an update on the pathophysiology of proteinuria, the pathways leading to fibrosis, and an overview of current and emerging therapies.

Kidney fibrosis study reveals causes, potential therapeutic target

Chronic kidney disease is a growing global health concern, affecting about 10 percent of the world’s population. A final, common pathway in chronic kidney disease is fibrosis, the formation of internal scar tissue, which can cause devastating effects. In the kidneys, it can ultimately lead to end-stage kidney failure.

Kidney fibrosis: from mechanisms to therapeutic medicines

Chronic kidney disease (CKD) is estimated to affect 10–14% of global population. Kidney fibrosis, characterized by excessive extracellular matrix deposition leading to scarring, is a hallmark manifestation in different progressive CKD; However, at present no antifibrotic therapies against CKD exist.

Mechanisms of Renal Fibrosis

Tubulointerstitial fibrosis is a chronic and progressive process affecting kidneys during aging and in chronic kidney disease (CKD), regardless of cause. CKD and renal fibrosis affect half of adults above age 70 and 10% of the world's population. Although no targeted therapy yet exists to slow renal fibrosis, a number of important recent advances have clarified the cellular and molecular mechanisms underlying the disease.

New Aspects of Kidney Fibrosis–From Mechanisms of Injury to Modulation of Disease

The major cellular player in the development and progression of kidney fibrosis is the myofibroblast. However, the cellular origin of renal myofibroblasts is still unclear. Up to now different cell types like fibroblasts, pericytes, proximal tubular epithelial cells, bone marrow-derived mesenchymal stem cells (MSC)...

Novel therapy to prevent and treat kidney fibrosis

Kidney fibrosis is the inevitable consequence of an excessive accumulation of extracellular matrix (ECM) that occurs in virtually all chronic kidney disease (CKD) leading to irreversible end stage kidney disease. Strategies that target one pathway contributing to kidney fibrosis have failed in numerous clinical trials. Hence new agents targeting novel pathways to limit kidney fibrosis are critically needed. The proposed strategy is not dependent on inhibiting a single pathway leading to fibrosis,

Renal fibrosis

Renal fibrosis, characterized by tubulointerstitial fibrosis and glomerulosclerosis, is the final manifestation of chronic kidney disease. Renal fibrosis is characterized by an excessive accumulation and deposition of extracellular matrix components. This pathologic result usually originates from both underlying complicated cellular activities such as epithelial-to-mesenchymal transition, fibroblast activation, monocyte/macrophage infiltration, and cellular apoptosis and the activation of signaling molecules such as transforming growth factor beta and angiotensin II. However, because the pathogenesis of renal fibrosis is extremely complicated and our knowledge regarding this condition is still limited, further studies are needed.

Renal Inflammation and Fibrosis: A Double-edged Sword

Renal tissue injury initiates inflammatory and fibrotic processes that occur to promote regeneration and repair. After renal injury, damaged tissue releases cytokines and chemokines, which stimulate activation and infiltration of inflammatory cells to the kidney. Normal tissue repair processes occur simultaneously with activation of myofibroblasts, collagen deposition, and wound healing responses; however, prolonged activation of pro-inflammatory and pro-fibrotic cell types causes excess extracellular matrix deposition.

The extracellular matrix in the kidney: a source of novel non-invasive biomarkers of kidney fibrosis?

At the moment renal biopsy is the only means of diagnosing renal interstitial fibrosis. Novel biomarkers should improve diagnosis of a disease, estimate its prognosis and assess the response to treatment, all in a non-invasive manner. Existing markers of CKD do not fully and specifically address these requirements and in particular do not specifically reflect renal fibrosis.

Treatment of Renal Fibrosis—Turning Challenges into Opportunities

Despite significant advances in our understanding of the mechanisms and molecular pathways in renal fibrosis derived from preclinical models, translation to clinical trials has remained poor. Major reasons are low sensitivity and few available parameters for end points in clinical trials, lack of diagnostic approaches to specifically, noninvasively and longitudinally assess kidney fibrosis, and insufficient patient selection and companion diagnostic.

VUMC scientists discover key step to kidney fibrosis

Researchers at Vanderbilt University Medical Center for the first time have shown that activation of the epidermal growth factor receptor (EGFR) is essential for the development of kidney fibrosis, tissue scarring following injury that can lead to kidney failure.

Resources

UK Renal Fibrosis Network

The Network is comprised of clinicians and scientists involved in research into the diagnosis, mechanisms, biomarkers and treatment of renal fibrosis. There is no fixed membership and anyone interested in this field is welcome to join the network.