Paricalcitol and endothelial function in chronic kidney disease trial

Hypertension. 2014 Nov;64(5):1005-11. doi: 10.1161/HYPERTENSIONAHA.114.03748. Epub 2014 Aug 4.


Altered vitamin D metabolism and low levels of the active form of this vitamin, 1,25-dihydroxy-vitamin D, is a hallmark of chronic kidney disease (CKD), but there is still no randomized controlled trial testing the effect of active forms of vitamin D on vascular function in patients with CKD. Paricalcitol and ENdothelial fuNction in chronic kidneY disease (PENNY) is a double-blinded randomized controlled trial (, NCT01680198) testing the effect of an active form of vitamin D, paricalcitol (2 μg/d×12 weeks) on endothelium-dependent and endothelium-independent vasodilatation in 88 patients with stage 3 to 4 CKD and parathormone >65 pg/mL (paricalcitol, n=44; placebo, n=44). Paricalcitol treatment reduced parathormone (-75 pg/mL; 95% confidence interval, -90 to -60), whereas parathormone showed a small rise during placebo (21 pg/mL; 95% confidence interval, 5-36). Blood pressure did not change in both study arms. Baseline flow-mediated dilation was identical in patients on paricalcitol (3.6±2.9%) and placebo (3.6±2.9%) groups. After 12 weeks of treatment, flow-mediated dilation rose in the paricalcitol but not in the placebo group, and the between-group difference in flow-mediated dilation changes (the primary end point, 1.8%; 95% confidence interval, 0.3-3.1%) was significant (P=0.016), and the mean proportional change in flow-mediated dilation was 61% higher in paricalcitol-treated patients than in placebo-treated patients. Such an effect was abolished 2 weeks after stopping the treatment. No effect of paricalcitol on endothelium-independent vasodilatation was registered. Paricalcitol improves endothelium-dependent vasodilatation in patients with stage 3 to 4 CKD. Findings in this study support the hypothesis that vitamin D may exert favorable effects on the cardiovascular system in patients with CKD.

Keywords: atherosclerosis; chronic kidney disease; endothelium; hypertension; paricalcitol; vitamin D.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / pharmacology*
  • Bone Density Conservation Agents / therapeutic use
  • Calcium / metabolism
  • Double-Blind Method
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology*
  • Ergocalciferols / adverse effects
  • Ergocalciferols / pharmacology*
  • Ergocalciferols / therapeutic use
  • Female
  • Glomerular Filtration Rate / drug effects
  • Glomerular Filtration Rate / physiology
  • Humans
  • Male
  • Middle Aged
  • Parathyroid Hormone / metabolism
  • Phosphates / metabolism
  • Renal Insufficiency, Chronic / drug therapy
  • Renal Insufficiency, Chronic / metabolism
  • Renal Insufficiency, Chronic / physiopathology*
  • Severity of Illness Index
  • Vasodilation / drug effects
  • Vasodilation / physiology


  • Bone Density Conservation Agents
  • Ergocalciferols
  • Parathyroid Hormone
  • Phosphates
  • paricalcitol
  • Calcium

Associated data