Vitamin D protection from rat diabetic nephropathy is partly mediated through Klotho expression and renin-angiotensin inhibition

Arch Physiol Biochem. 2018 Dec;124(5):461-467. doi: 10.1080/13813455.2018.1423624. Epub 2018 Jan 8.

Abstract

Objective: We hypothesised that vitamin D has a beneficial renal protective effect from diabetic nephropathy (DN).

Methods: Four rat groups were included: normal control (control), type 2 diabetes for eight weeks (DM), treated group with angiotensin receptor blocker losartan (DM + L), and vitamin D-treated group started from the onset of diabetes (DM + Vit D).

Results: In the both treated groups, we found a significant (p < .05) reduction in the renal pro-inflammatory and profibrotic markers induced by diabetes. Vitamin D caused more reduction in monocyte chemoattractant protein-1 (MCP-1), transforming growth factor (TGFβ-1), and renin-angiotensin levels that gave better kidney function compared to the DM + L group.

Conclusion: Vitamin D may have a valuable role in the renal protective effect from DN, this may occur via expression of its VDR, Klotho and blocking renin-angiotensin activation, so vitamin D should be considered as a target in renal prophylactic measures against DN.

Keywords: Klotho; Vitamin D; diabetic nephropathy; losartan.

Publication types

  • Comparative Study

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / therapy
  • Diabetic Nephropathies / immunology
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / physiopathology
  • Diabetic Nephropathies / prevention & control*
  • Dietary Supplements*
  • Down-Regulation
  • Gene Expression Regulation*
  • Glucuronidase / chemistry
  • Glucuronidase / genetics
  • Glucuronidase / metabolism*
  • Kidney / drug effects
  • Kidney / immunology
  • Kidney / metabolism*
  • Kidney / physiopathology
  • Klotho Proteins
  • Losartan / therapeutic use
  • Male
  • Random Allocation
  • Rats, Wistar
  • Receptors, Calcitriol / agonists
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism
  • Renal Insufficiency / complications
  • Renal Insufficiency / immunology
  • Renal Insufficiency / metabolism
  • Renal Insufficiency / prevention & control*
  • Renin-Angiotensin System / drug effects
  • Reproducibility of Results
  • Vitamin D / therapeutic use*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers
  • Receptors, Calcitriol
  • Vitamin D
  • Glucuronidase
  • Klotho Proteins
  • Losartan