Vitamin D deficiency contributes to vascular damage in sustained ischemic acute kidney injury

Ana C. de Bragança, Rildo A. Volpini, Purvi Mehrotra, Lúcia Andrade, David P. Basile

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Reductions in renal microvasculature density and increased lymphocyte activity may play critical roles in the progression of chronic kidney disease (CKD) following acute kidney injury (AKI) induced by ischemia/reperfusion injury (IRI). Vitamin D deficiency is associated with tubulointerstitial damage and fibrosis progression following IRI-AKI. We evaluated the effect of vitamin D deficiency in sustained IRI-AKI, hypothesizing that such deficiency contributes to the early reduction in renal capillary density or alters the lymphocyte response to IRI. Wistar rats were fed vitamin D-free or standard diets for 35 days. On day 28, rats were randomized into four groups: control, vitamin D deficient (VDD), bilateral IRI, and VDD+IRI. Indices of renal injury and recovery were evaluated for up to 7 days following the surgical procedures. VDD rats showed reduced capillary density (by cablin staining), even in the absence of renal I/R. In comparison with VDD and IRI rats, VDD+IRI rats manifested a significant exacerbation of capillary rarefaction as well as higher urinary volume, kidney weight/body weight ratio, tissue injury scores, fibroblast-specific protein-1, and alpha-smooth muscle actin. VDD+IRI rats also had higher numbers of infiltrating activated CD4+ and CD8+ cells staining for interferon gamma and interleukin-17, with a significant elevation in the Th17/T-regulatory cell ratio. These data suggest that vitamin D deficiency impairs renal repair responses to I/R injury, exacerbates changes in renal capillary density, as well as promoting fibrosis and inflammation, which may contribute to the transition from AKI to CKD.

Original languageEnglish (US)
Article numbere12829
JournalPhysiological reports
Volume4
Issue number13
DOIs
StatePublished - Jul 1 2016

Keywords

  • Acute kidney injury
  • CD4 lymphocytes
  • CD8 lymphocytes
  • T-reg cells
  • cytokines
  • ischemia reperfusion injury
  • renal microvascular density
  • vitamin D deficiency

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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