[Selective vitamin D receptor activation: effect on renal physiopathology].
The wide distribution of the vitamin D receptor (VDR) suggests that its activators (VDRAs) are involved in diverse organ functions including the cardiovascular, immune, and reproductive systems. These actions are likely to be independent of PTH and calcium/phosphorus levels. Earlier studies had shown that calcitriol was able to favorably influence experimental nephritis, remnant kidney glomerulosclerosis, and interstitial fibrosis, mediated through inhibition of inflammatory cytokines. Recently, VDRAs were shown to inhibit the reninangiotensin system (RAS), acting directly on the renin gene promoter. This action is independent of the systemic RAS blockade. VDRAs also inhibit other important gene promoters including NF-kB and p65, which are known to foster inflammation and fibrogenesis. These multiple actions result in a decrease in macrophage infiltration, fibroblast activation, and endothelial mesenchymal transition in the kidney. These findings represent the rationale for the use of VDRAs, in association with RAS blocking agents, to counteract the progression of renal injury characterized by inflammation and neofibrogenesis. However, despite promising preliminary results, the human studies available to date do not allow to draw definitive conclusions on this matter.
Marangella
M
M
S.C. Nefrologia e Dialisi, A.O. Ordine Mauriziano-Torino, Torino - Italy. mmarangella@mauriziano.it
Berutti
S
S
Fabbrini
L
L
D002117:Calcitriol / Q000494:pharmacology / Q000627:therapeutic use*; D002120:Calcium Channel Agonists / Q000627:therapeutic use*; D019317:Evidence-Based Medicine; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000517:prevention & control; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects; D018167:Receptors, Calcitriol / Q000187:drug effects* / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D051996:Transcription Factor RelA / Q000187:drug effects
D002120:Calcium Channel Agonists; D016328:NF-kappa B; D018167:Receptors, Calcitriol; D051996:Transcription Factor RelA; D002117:Calcitriol