title: Vitamin D deficiency is a potential risk factor for contrast-induced nephropathy.
abstract: Vitamin D deficiency (VDD) is widespread in the general population. Iodinated (IC) or gadolinium-based contrast media (Gd) may decrease renal function in high-risk patients. This study tested the hypothesis that VDD is a predisposing factor for IC- or Gd-induced nephrotoxicity. To this end, male Wistar rats were fed standard (SD) or vitamin D-free diet for 30 days. IC (diatrizoate), Gd (gadoterate meglumine), or 0.9% saline was then administered intravenously and six groups were obtained as the following: SD plus 0.9% saline (Sham-SD), SD plus IC (SD+IC), SD plus Gd (SD+Gd), vitamin D-free diet for 30 days plus 0.9% saline (Sham-VDD30), vitamin D-free diet for 30 days plus IC (VDD30+IC), and vitamin D-free diet for 30 days plus Gd (VDD30+Gd). Renal hemodynamics, redox status, histological, and immunoblot analysis were evaluated 48 h after contrast media (CM) or vehicle infusion. VDD rats showed lower levels of total serum 25-hydroxyvitamin D [25(OH)D], similar plasma calcium and phosphorus concentration, and higher renal renin and angiotensinogen protein expression compared with rats fed SD. IC or Gd infusion did not affect inulin clearance-based estimated glomerular filtration rate (GFR) in rats fed SD but significantly decreased GFR in rats fed vitamin D-free diet. Both CM increased renal angiotensinogen, and the interaction between VDD and CM triggered lower renal endothelial nitric oxide synthase abundance and higher renal thiobarbituric acid reactive substances-to-glutathione ratio (an index of oxidative stress) on VDD30+IC and VDD30+Gd groups. Conversely, worsening of renal function was not accompanied by abnormalities on kidney structure. Additionally, rats on a VDD for 60 days displayed a greater fall in GFR after CM administration. Collectively, our findings suggest that VDD is a potential risk factor for IC- or Gd-induced nephrotoxicity most likely due to imbalance in intrarenal vasoactive substances and oxidative stress.
authors.affiliation: Medical Investigation Laboratory 12, Division of Nephrology, University of São Paulo Medical School, São Paulo, Brazil; Division of Nephrology, Federal University of Espírito Santo, Vitória, Brazil; and wmluchi@usp.br.
authors.forename: Weverton M
authors.initials: WM
authors.lastname: Luchi
authors.affiliation: Medical Investigation Laboratory 12, Division of Nephrology, University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Maria Heloisa M
authors.initials: MH
authors.lastname: Shimizu
authors.affiliation: Medical Investigation Laboratory 12, Division of Nephrology, University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Daniele
authors.initials: D
authors.lastname: Canale
authors.affiliation: Medical Investigation Laboratory 12, Division of Nephrology, University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Pedro Henrique F
authors.initials: PH
authors.lastname: Gois
authors.affiliation: Medical Investigation Laboratory 12, Division of Nephrology, University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: de Bragança
authors.affiliation: Medical Investigation Laboratory 12, Division of Nephrology, University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Rildo A
authors.initials: RA
authors.lastname: Volpini
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Adriana C C
authors.initials: AC
authors.lastname: Girardi
authors.affiliation: Medical Investigation Laboratory 12, Division of Nephrology, University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Seguro
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000009:adverse effects*; D003928:Diabetic Nephropathies / Q000139:chemically induced*; D004195:Disease Models, Animal; D005682:Gadolinium / Q000009:adverse effects*; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D017208:Rats, Wistar; D012307:Risk Factors; D014807:Vitamin D / Q000031:analogs & derivatives / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000378:metabolism*
chemical_list: D003287:Contrast Media; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D005682:Gadolinium
keywords: contrast-induced nephropathy; gadolinium; oxidative stress; renin-angiotensin system; vitamin D deficiency