Role of Vitamin D in Maintaining Renal Epithelial Barrier Function in Uremic Conditions

Int J Mol Sci. 2017 Nov 26;18(12):2531. doi: 10.3390/ijms18122531.


As current kidney replacement therapies are not efficient enough for end-stage renal disease (ESRD) treatment, a bioartificial kidney (BAK) device, based on conditionally immortalized human proximal tubule epithelial cells (ciPTEC), could represent an attractive solution. The active transport activity of such a system was recently demonstrated. In addition, endocrine functions of the cells, such as vitamin D activation, are relevant. The organic anion transporter 1 (OAT-1) overexpressing ciPTEC line presented 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1) and vitamin D receptor (VDR), responsible for vitamin D activation, degradation and function, respectively. The ability to produce and secrete 1α,25-dihydroxy-vitamin D₃, was shown after incubation with the precursor, 25-hydroxy-vitamin D₃. The beneficial effect of vitamin D on cell function and behavior in uremic conditions was studied in the presence of an anionic uremic toxins mixture. Vitamin D could restore cell viability, and inflammatory and oxidative status, as shown by cell metabolic activity, interleukin-6 (IL-6) levels and reactive oxygen species (ROS) production, respectively. Finally, vitamin D restored transepithelial barrier function, as evidenced by decreased inulin-FITC leakage in biofunctionalized hollow fiber membranes (HFM) carrying ciPTEC-OAT1. In conclusion, the protective effects of vitamin D in uremic conditions and proven ciPTEC-OAT1 endocrine function encourage the use of these cells for BAK application.

Keywords: bioartificial kidney; chronic kidney disease; conditionally immortalized proximal tubule cells; end-stage renal disease; epithelial barrier; uremic toxins; vitamin D.

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism
  • Cell Line
  • Cell Survival
  • Cytoprotection
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Humans
  • Interleukin-6 / metabolism
  • Kidney Tubules, Proximal / cytology
  • Organic Anion Transport Protein 1 / metabolism
  • Oxidative Stress
  • Receptors, Calcitriol / metabolism
  • Toxins, Biological / toxicity*
  • Vitamin D / pharmacology*
  • Vitamin D3 24-Hydroxylase / metabolism
  • Vitamins / pharmacology*


  • Interleukin-6
  • Organic Anion Transport Protein 1
  • Receptors, Calcitriol
  • Toxins, Biological
  • Vitamins
  • uremia middle molecule toxins
  • Vitamin D
  • CYP24A1 protein, human
  • Vitamin D3 24-Hydroxylase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • CYP27B1 protein, human