The role of tubulointerstitial inflammation in the progression of chronic renal failure.
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 κB 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)(2)D(3) 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.
Rodríguez-Iturbe
Bernardo
B
Servicio de Nefrología, Hospital Universitario de Maracaibo, Universidad del Zulia and Centro de Investigaciones Biomédicas, Instituto Venezolano de Investigaciones Científicas (IVIC-Zulia), Maracaibo, Venezuela. bernardori@telcel.net6.ve
García García
Guillermo
G
D000818:Animals; D018450:Disease Progression; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology*; D009395:Nephritis, Interstitial / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology; D011507:Proteinuria / Q000378:metabolism / Q000473:pathology