Effect of calcitriol treatment on arterial stiffness in people with type 2 diabetes and stage 3 chronic kidney disease

TY - JOUR

T1 - Effect of calcitriol treatment on arterial stiffness in people with type 2 diabetes and stage 3 chronic kidney disease

AU - Karalliedde, Janaka

AU - Fountoulakis, Nikolaos

AU - Corcillo, Antonella

AU - Maltese, Giuseppe

AU - Flaquer, Maria

AU - Stathi, Dimitra

AU - Mangelis, Anastasios

AU - Panagiotou, Angeliki

AU - Ayis, Salma

AU - Thomas, Stephen

AU - Gnudi, Luigi

N1 - Funding Information: The study was funded by a research grant from Diabetes UK (09/0003886). We wish to thank the support and help of Professor Martin Gulliford (School of Population Health & Environmental Sciences, King's College London) and the trial data monitoring committee, which included Dr Peter Watkins, Dr Phil Chowienczyk and Dr Richard Hooper. S.A. was funded/supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. We also thank the research nurses and participants who assisted in this work. Funding Information: The study was funded by a research grant from Diabetes UK (09/0003886). We wish to thank the support and help of Professor Martin Gulliford (School of Population Health & Environmental Sciences, King's College London) and the trial data monitoring committee, which included Dr Peter Watkins, Dr Phil Chowienczyk and Dr Richard Hooper. S.A. was funded/supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. We also thank the research nurses and participants who assisted in this work. Publisher Copyright: © 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

PY - 2023/1

Y1 - 2023/1

N2 - Aims: Active vitamin D deficiency is associated with increased aortic-pulse wave velocity (Ao-PWV) in people with type 2 diabetes (T2DM) and chronic kidney disease (CKD). There are no randomised controlled trials investigating the effect of active vitamin D treatment on Ao-PWV in people with T2DM and CKD. Methods: A 48-week duration single-centre randomised double-blind parallel-group trial examined the impact of oral 1,25 dihydroxyvitamin D (calcitriol 0.25 mcg OD) as compared to placebo on a primary endpoint of Ao-PWV. People with T2DM and stable stage 3 CKD with intact parathyroid hormone (iPTH) level >30 pg/mL were eligible. Results: In total, 127 (70% male) people were randomised (calcitriol n = 64 or placebo n = 63). There was no change in Ao-PWV observed, mean ± standard deviation (SD), in the calcitriol group of 11.79 (±2.5) to 12.08 (3.0) m/s as compared to 10.90 (±2.4) to 11.39 (±2.6) m/s with placebo. The between-treatment group adjusted mean (95% confidence interval [(CI]] change was 0.23 (−0.58 to 1.05) m/s, P =.57. No effect of calcitriol was observed on central arterial pressures, albuminuria, serum calcium or phosphate levels. However, iPTH fell with calcitriol treatment (mean [95% CI] between-group difference of −27.8 (−42.3 to −13.2) pg/mL, P <.001. Conclusion: In T2DM and stage 3 CKD, calcitriol as compared to placebo does not improve Ao-PWV or other markers of arterial stiffness. Our study does not provide evidence for the use of active vitamin D for improving arterial stiffness in T2DM with stage 3 CKD.

AB - Aims: Active vitamin D deficiency is associated with increased aortic-pulse wave velocity (Ao-PWV) in people with type 2 diabetes (T2DM) and chronic kidney disease (CKD). There are no randomised controlled trials investigating the effect of active vitamin D treatment on Ao-PWV in people with T2DM and CKD. Methods: A 48-week duration single-centre randomised double-blind parallel-group trial examined the impact of oral 1,25 dihydroxyvitamin D (calcitriol 0.25 mcg OD) as compared to placebo on a primary endpoint of Ao-PWV. People with T2DM and stable stage 3 CKD with intact parathyroid hormone (iPTH) level >30 pg/mL were eligible. Results: In total, 127 (70% male) people were randomised (calcitriol n = 64 or placebo n = 63). There was no change in Ao-PWV observed, mean ± standard deviation (SD), in the calcitriol group of 11.79 (±2.5) to 12.08 (3.0) m/s as compared to 10.90 (±2.4) to 11.39 (±2.6) m/s with placebo. The between-treatment group adjusted mean (95% confidence interval [(CI]] change was 0.23 (−0.58 to 1.05) m/s, P =.57. No effect of calcitriol was observed on central arterial pressures, albuminuria, serum calcium or phosphate levels. However, iPTH fell with calcitriol treatment (mean [95% CI] between-group difference of −27.8 (−42.3 to −13.2) pg/mL, P <.001. Conclusion: In T2DM and stage 3 CKD, calcitriol as compared to placebo does not improve Ao-PWV or other markers of arterial stiffness. Our study does not provide evidence for the use of active vitamin D for improving arterial stiffness in T2DM with stage 3 CKD.

UR - http://www.scopus.com/inward/record.url?scp=85136595172&partnerID=8YFLogxK

U2 - 10.1111/bcp.15484

DO - 10.1111/bcp.15484

M3 - Article

SN - 0306-5251

VL - 89

SP - 279

EP - 289

JO - British Journal of Clinical Pharmacology

JF - British Journal of Clinical Pharmacology

IS - 1

ER -