Effect of paricalcitol on endothelial function and inflammation in type 2 diabetes and chronic kidney disease

J Diabetes Complications. 2015 Apr;29(3):433-7. doi: 10.1016/j.jdiacomp.2015.01.004. Epub 2015 Jan 13.

Abstract

Aims: Patients with type 2 diabetes (T2DM) and chronic kidney disease (CKD) have impaired endothelial function. Vitamin D and its analogs may play a role in regulation of endothelial function and inflammation. We studied effects of paricalcitol compared to placebo on endothelial function and markers of inflammation and oxidative stress in patients with T2DM and CKD.

Methods: A double blind, randomized, placebo-controlled trial was conducted in 60 patients with T2DM and stage 3 or 4 CKD. Paricalcitol 1 mcg or placebo was administered orally once daily for three months. Brachial artery flow mediated dilatation (FMD), nitroglycerine mediated dilation (NMD), and plasma concentrations of inflammatory cytokines, tumor necrosis factor -α and interleukin-6, highly-sensitive C-reactive protein; endothelial surface proteins, intercellular adhesion molecule -1 and monocyte chemo attractant protein-1, and plasma glucose, insulin, free fatty acids, and urinary isoprostane were measured at baseline and end of three months.

Results: 27 patients in the paricalcitol group and 28 patients in the control group completed the study, though analysis of FMD at both time points was possible in 23 patients in each group. There was no significant difference in the change in FMD, NMD or the biomarkers examined after paricalcitol or placebo treatment.

Conclusions: Treatment with paricalcitol at this dose and duration did not affect brachial artery FMD or biomarkers of inflammation and oxidative stress. The lack of significance may be due to the fact that the study patients had advanced CKD and that effects of paricalcitol are not additive to the effects of glycemic, lipid and anti-hypertensive therapies.

Keywords: Chronic kidney disease; Diabetes mellitus; Endothelial dysfunction; Inflammation; Paricalcitol.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood Glucose / metabolism
  • C-Reactive Protein / analysis
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / complications
  • Diabetic Nephropathies / drug therapy
  • Diabetic Nephropathies / physiopathology
  • Double-Blind Method
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Ergocalciferols / pharmacology
  • Ergocalciferols / therapeutic use*
  • Female
  • Humans
  • Inflammation / complications
  • Inflammation / drug therapy*
  • Inflammation / physiopathology
  • Insulin / blood
  • Male
  • Middle Aged
  • Placebos
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / physiopathology
  • Young Adult

Substances

  • Blood Glucose
  • Ergocalciferols
  • Insulin
  • Placebos
  • paricalcitol
  • C-Reactive Protein