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.

Keywords: contrast-induced nephropathy; gadolinium; oxidative stress; renin-angiotensin system; vitamin D deficiency.