Vitamin D protects against diabetic nephropathy: Evidence-based effectiveness and mechanism

Eur J Pharmacol. 2019 Feb 15;845:91-98. doi: 10.1016/j.ejphar.2018.09.037. Epub 2018 Oct 1.

Abstract

Vitamin D has been suggested to harbor multiple biological activities, among them the potential of vitamin D in the protection of diabetic nephropathy (DN) has attracted special attention. Both animal studies and clinical trials have documented an inverse correlation between low vitamin D levels and DN risk, and supplementation with vitamin D or its active derivatives has been demonstrated to improve endothelial cell injury, reduce proteinuria, attenuate renal fibrosis, and resultantly retard DN progression. Vitamin D exerts its pharmacological effects primarily via vitamin D receptor, whose activation inhibits the renin-angiotensin system, a key culprit for DN under hyperglycemia. The anti-DN benefit of vitamin D can be enhanced when administrated in combination with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers. Mechanistic studies reveal that pathways relevant to inflammation participate in the pathogenesis of DN, however, consumption of vitamin D-related products negatively regulates inflammatory response at multiple levels, indicated by inhibiting macrophage infiltration, nuclear factor-kappa B (NF-κB) activation, and production of such inflammatory mediators as transforming growth factor-β(TGF-β), monocyte chemoattractant protein 1(MCP-1), and regulated upon activation normal T cell expressed and secreted protein(RANTES). The robust anti-inflammatory property of vitamin D-related products allows them with a promising renoprotective therapeutic option for DN. This review summarizes new advances in our understanding of vitamin D-related products in the DN management.

Keywords: Diabetic nephropathy; Inflammation; Vitamin D; Vitamin D receptor.

Publication types

  • Review

MeSH terms

  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Animals
  • Chemokine CCL2 / drug effects
  • Chemokine CCL5 / drug effects
  • Diabetic Nephropathies / drug therapy*
  • Drug Therapy, Combination
  • Endothelial Cells / drug effects*
  • Endothelial Cells / pathology
  • Humans
  • NF-kappa B / drug effects
  • Protective Agents / pharmacology
  • Proteinuria / drug therapy*
  • Receptors, Calcitriol / metabolism*
  • Renin-Angiotensin System / drug effects*
  • Transforming Growth Factor beta / drug effects
  • Vitamin D / pharmacology
  • Vitamin D / therapeutic use*

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Chemokine CCL2
  • Chemokine CCL5
  • NF-kappa B
  • Protective Agents
  • Receptors, Calcitriol
  • Transforming Growth Factor beta
  • Vitamin D