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Molecular Developments in the Treatment of Renal Fibrosis

  • Chapter
Fibrogenesis: Cellular and Molecular Basis

Part of the book series: Medical Intelligence Unit ((MIUN))

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Abstract

Progressive renal disease is associated with the development of fibrosing lesions not only in the glomerulus, but also in the interstitial and vascular compartments of the kidney, in a process that involves the mesenchymally derived, phenotypically similar, mesangial cell, myofibroblast and vascular smooth muscle cell. The similarities in the pathogenesis of all three processes means that the search for rational treatment strategies for any one may be of universal benefit to the others.

Potential therapeutic strategies target fibrosis both indirectly and directly. Indirect therapies alter the environment the kidney operates in such as by controlling blood pressure, hyperlipidemia and hyperglycaemia. As our understanding of the mechanisms of fibrosis increase, we are developing more direct treatment strategies that target the vasoactive mediators, growth factors and cell signaling pathways that regulate renal fibrogenesis. Finally attempts to increase collagen degradation and maintain blood supply are likely to reduce the damage resulting from aberrant collagen synthesis.

The continuing advances in cellular and molecular biology mean that we are becoming more aware of how cells interrelate with each other and their environment. Measures that specifically interfere with fibrosis can therefore be expected to improve prognosis not only in progressive renal failure but also in progressive fibrosing diseases in many other organs.

Progressive renal disease is associated with the concurrent development of fibrosing lesions not only in the glomerulus, but also in the interstitial and vascular compartments of the kidney (Fig. 1). Though attention is usually directed separately to the three processes—glomerulosclerosis, tubulointerstitial fibrosis and vascular sclerosis—all three eventually occur and the fundamental pathology is similar.

Renal fibrosis or sclerosis refers to the replacement of renal parenchyma with connective tissue, in a process that resembles the generalised chronic inflammation that occurs elsewhere. Initiating injury, recruitment of inflammatory cells (neutrophils, macrophages, T-cells), generation and release of profibrotic growth factors, proliferation and matrix synthesis, and finally matrix remodelling are the sequential but overlapping events. Increases in both the number and activity of matrix producing cells is responsible for matrix deposition, with the balance between this and remodelling determining the extent of scarring.

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  1. Department of Nephrology The Royal Melbourne Hospital and Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia

    Gavin J. Becker & Tim D. Hewitson

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Becker, G.J., Hewitson, T.D. (2005). Molecular Developments in the Treatment of Renal Fibrosis. In: Fibrogenesis: Cellular and Molecular Basis. Medical Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-26476-0_6

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