There is compelling evidence that interstitial inflammation plays a central role in the loss of renal function in chronic renal disease. The combined effects of interstitial inflammation, oxidative stress and local angiotensin II activity result in the disruption of glomerulus-tubule continuity, the development of pathogenic hypoxia, the generation of myofibroblasts and fibrosis, and the impairment of the protective autoregulation of glomerular blood flow that leads to glomerulosclerosis. The association between proteinuria and progression of chronic kidney disease is firmly established. Proximal tubular cells (PTC) exposed to high concentration of proteins produce proinflammatory and profibrotic factors. The activation of nuclear factor ĸB and the signal transducer and activator of transcription results in the upregulation of a variety of cytokines and chemokines, overexpression of adhesion molecules and interstitial infiltration of inflammatory cells. Fibrosis is promoted by release of transforming growth factor β, which induces myofibroblast formation and collagen deposition. Finally, the participation of vitamin D3 deficiency in the development of tubulointerstitial fibrosis is reviewed. The molecule 1,25-(OH)2D3 modulates PTC proliferation, suppresses fibroblast activation and matrix production, reduces epithelial mesenchymal transition and downregulates the genes of the renin-angiotensin system, which are critical steps in the development of a scarred kidney.
World Kidney Day on March 8th 2012 provides a chance to reflect on the success of kidney transplantation as a therapy for end stage kidney disease that surpasses dialysis treatments both for the quality and quantity of life that it provides and for its cost effectiveness. Anything that is both cheaper and better, but is not actually the dominant therapy, must have other drawbacks that prevent replacement of all dialysis treatment by transplantation. The barriers to universal transplantation as the therapy for end stage kidney disease include the economic limitations which, in some countries place transplantation, appropriately, at a lower priority than public health fundamentals such as clean water, sanitation and vaccination. Even in high income countries the technical challenges of surgery and the consequences of immunosuppression restrict the number of suitable recipients, but the major finite restrictions on kidney transplantation rates are the shortage of donated organs and the limited medical, surgical and nursing workforces with the required expertise. These problems have solutions which involve the full range of societal, professional, governmental and political environments. World Kidney Day is a call to deliver transplantation therapy to the one million people a year who have a right to benefit.
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