title: Vitamin D deficiency aggravates ischemic acute kidney injury in rats.
abstract: Vitamin D deficiency (VDD) increases the risk of death in hospitalized patients. Renal ischemia/reperfusion injury (IRI) induces acute kidney injury (AKI), which activates cell cycle inhibitors, including p21, a cyclin-dependent kinase inhibitor and genomic target of 25-hydroxyvitamin D, which is in turn a potent immunomodulator with antiproliferative effects. In this study, we assess the impact of VDD in renal IRI. Wistar rats were divided into groups, each evaluated for 30 days: control (receiving a standard diet); VDD (receiving a vitamin D-free diet); IRI (receiving a standard diet and subjected to 45-min bilateral renal ischemia on day 28); and VDD + IRI (receiving a vitamin D-free diet and subjected to 45-min bilateral renal ischemia on day 28). At 48 h after IRI, animals were euthanized; blood, urine, and kidney tissue samples were collected. Compared with IRI rats, VDD + IRI rats showed a more severe decrease in glomerular filtration rate, greater urinary protein excretion, a higher kidney/body weight ratio and lower renal aquaporin 2 expression, as well as greater morphological damage, characterized by increased interstitial area and tubular necrosis. Our results suggest that the severity of tubular damage in IRI may be associated with downregulation of vitamin D receptors and p21. VDD increases renal inflammation, cell proliferation and cell injury in ischemic AKI.
authors.affiliation: Division of Nephrology, Laboratory of Basic Science LIM-12 University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Ana Carolina
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: Division of Nephrology, Laboratory of Basic Science LIM-12 University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Daniele
authors.initials: D
authors.lastname: Canale
authors.affiliation: Division of Nephrology, Laboratory of Basic Science LIM-12 University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Janaína G
authors.initials: JG
authors.lastname: Gonçalves
authors.affiliation: Division of Nephrology, Laboratory of Basic Science LIM-12 University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Maria Heloisa M
authors.initials: MH
authors.lastname: Shimizu
authors.affiliation: Division of Nephrology, Laboratory of Basic Science LIM-12 University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Talita R
authors.initials: TR
authors.lastname: Sanches
authors.affiliation: Division of Nephrology, Laboratory of Basic Science LIM-12 University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Seguro
authors.affiliation: Division of Nephrology, Laboratory of Basic Science LIM-12 University of São Paulo School of Medicine, São Paulo, Brazil luciacan@usp.br.
authors.forename: Lúcia
authors.initials: L
authors.lastname: Andrade
keywords: Acute kidney injury; cyclin‐dependent kinase inhibitor p21; vitamin D deficiency; vitamin D receptors