title: Vitamin D deficiency contributes to vascular damage in sustained ischemic acute kidney injury.
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.
authors.affiliation: Division of Nephrology, Laboratory of Basic Science LIM-12, University of São Paulo School of Medicine, São Paulo, Brazil ana.braganca@hc.fm.usp.br.
authors.forename: Ana C
authors.initials: AC
authors.lastname: de Bragança
authors.affiliation: Division of Nephrology, Laboratory of Basic Science LIM-12, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Rildo A
authors.initials: RA
authors.lastname: Volpini
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Purvi
authors.initials: P
authors.lastname: Mehrotra
authors.affiliation: Division of Nephrology, Laboratory of Basic Science LIM-12, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Lúcia
authors.initials: L
authors.lastname: Andrade
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: David P
authors.initials: DP
authors.lastname: Basile
mesh_terms: D000199:Actins / Q000378:metabolism; D058186:Acute Kidney Injury / Q000150:complications / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002196:Capillaries / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007668:Kidney / Q000098:blood supply* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D009393:Nephritis / Q000209:etiology / Q000473:pathology; D017208:Rats, Wistar; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000473:pathology; D015427:Reperfusion Injury / Q000150:complications / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014808:Vitamin D Deficiency / Q000150:complications / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
chemical_list: D000199:Actins; D002135:Calcium-Binding Proteins; D007371:Interferon-gamma; D020381:Interleukin-17; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C579666:FSP1 protein, rat; C499412:S100a4 protein, rat; C498862:Acta2 protein, rat
keywords: Acute kidney injury; CD4+ lymphocytes; CD8+ lymphocytes; T‐reg cells; cytokines; ischemia reperfusion injury; renal microvascular density; vitamin D deficiency