Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2017 Oct 4;12(10):e0185449.
doi: 10.1371/journal.pone.0185449. eCollection 2017.

Vitamin D and methylarginines in chronic kidney disease (CKD)

Claudia Torino  1 , Patrizia Pizzini  1 , Sebastiano Cutrupi  1 , Rocco Tripepi  1 , Giovanni Tripepi  1 , Francesca Mallamaci  1 , Carmine Zoccali  1
Affiliations
Randomized Controlled Trial

Vitamin D and methylarginines in chronic kidney disease (CKD)

Claudia Torino et al. PLoS One. .

Abstract

Background: Vitamin D associates with the plasma concentration of the endogenous inhibitor of the nitric oxide system asymmetric dimethyl arginine (ADMA) and cross-sectional studies in CKD patients treated with the vitamin D receptor activator paricalcitol show that plasma ADMA is substantially less than in those not receiving this drug.

Methods: In the frame of a randomized, double-blind, placebo controlled trial, the Paracalcitol and ENdothelial fuNction in chronic kidneY disease (PENNY), we investigated whether vitamin D receptor activation by paricalcitol (2 μg/day x 12 weeks) affects the plasma concentration of ADMA and symmetric dimethyl arginine (SDMA) in 88 patients with stage 3 to 4 CKD.

Results: Paricalcitol produced the expected small rise in serum calcium and phosphate and a marked PTH suppression. However, ADMA [Paricalcitol: baseline 0.75 μMol/L (95%CI: 0.70-0.81), 12 week 0.72 μMol/L (95%CI: 0.66-0.78); Placebo: baseline 0.75 μMol/L (95%CI: 0.70-0.90) 12 weeks 0.70 μMol/L (95%CI: 0.66-0.74)] and SDMA [Paricalcitol: baseline 0.91 μMol/L (95%CI: 0.82-1.00), 12 week 0.94 μMol/L (95%CI: 0.82-0.1.06); Placebo: baseline 0.91 μMol/L (95%CI: 0.82-1.06) 12 weeks 0.99 μMol/L (95%CI: 0.88-1.10)] remained unchanged during the trial and 2 weeks after stopping these treatments.

Conclusions: Paricalcitol does not modify plasma ADMA and SDMA in patients with stage 3-4 CKD. The apparent beneficial effects of paricalcitol on ADMA registered in cross-sectional studies is likely attributable to confounding by indication rather than to a true effect of this drug on ADMA metabolism.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: CZ received honoraria for lectures from AbbVie, Amgen, Genzyme, Roche, Shire. FM received honoraria for lectures by Amgen and Shire and GT by AbbVie. The other authors report no conflict of interest.This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Changes in bone mineral disorder biomarkers, ADMA and SDMA according to the treatment group (paricalcitol/placebo).
The bars correspond to 95%CI.
See this image and copyright information in PMC

References

    1. Böger RH, Maas R, Schulze F, Schwedhelm E. Asymmetric dimethylarginine (ADMA) as a prospective marker of cardiovascular disease and mortality—An update on patient populations with a wide range of cardiovascular risk. Pharmacol Res. 2009;60: 481–487. doi: 10.1016/j.phrs.2009.07.001 - DOI - PubMed
    1. Schwedhelm E, Böger RH. The role of asymmetric and symmetric dimethylarginines in renal disease. Nat Rev Nephrol. Nature Publishing Group; 2011;7: 275–85. doi: 10.1038/nrneph.2011.31 - DOI - PubMed
    1. Selley ML. Increased concentrations of homocysteine and asymmetric dimethylarginine and decreased concentrations of nitric oxide in the plasma of patients with Alzheimer’s disease. Neurobiol Aging. 2003;24: 903–907. doi: 10.1016/S0197-4580(03)00007-1 - DOI - PubMed
    1. Stühlinger MC, Abbasi F, Chu JW, Lamendola C, McLaughlin TL, Cooke JP, et al. Relationship between insulin resistance and an endogenous nitric oxide synthase inhibitor. JAMA. 2002;287: 1420–6. - PubMed
    1. Hermenegildo C, Medina P, Peiró M, Segarra G, Vila JM, Ortega J, et al. Plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is elevated in hyperthyroid patients. J Clin Endocrinol Metab. 2002;87: 5636–5640. doi: 10.1210/jc.2002-020905 - DOI - PubMed

Publication types