Comparative Effects of Cholecalciferol and Calcitriol on Circulating Markers of CKD Mineral Bone Disorder

Zelnick, Leila R.; Kestenbaum, Bryan; Chonchol, Michel; Kendrick, Jessica

doi:10.2215/cjn.00480118

Cited by 7 publications

(5 citation statements)

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“…Ideally, clinically useful biomarkers should be modifiable and identify which patients derive clinical benefit from available therapeutic interventions, such as vitamin D supplementation. We and other investigators have shown that cholecalciferol, ergocalciferol, 1,25(OH)2D3, or paricalcitol each increase the circulating VDMR ratio 57, 58, 59, 60. The increase in serum VDMR ratio observed in this study among CRIC participants who initiated cholecalciferol between study year 1 and 4 is consistent with this literature.…”

Section: Discussionsupporting

confidence: 91%

Vitamin D Metabolic Ratio and Risks of Death and CKD Progression

Bansal

Katz

Appel

et al. 2019

Kidney International Reports

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IntroductionAssessment of impaired vitamin D metabolism is limited by lack of functional measures. CYP24A1-mediated vitamin D clearance, calculated as the ratio of serum 24,25-dihydroxyvitamin D3 to 25-hydroxyvitamin D3 (the vitamin D metabolic ratio, VDMR), is induced by 1,25-dihydroxyvitamin D and may assess tissue-level activity. We tested associations of the VDMR with risks of death and progression to end-stage renal disease (ESRD) in patients with chronic kidney disease (CKD).MethodsWe studied participants from the Chronic Renal Insufficiency Cohort (CRIC), which included a random subset of 1080 CRIC participants plus additional participants who experienced ESRD or died (case cohort study design). Serum 24,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 was measured 1 year after enrollment. The primary outcomes included death and progression to ESRD. Using inverse probability weighting, we tested associations of VDMR (24,25[OH]2D3/25[OH]D3) with risks of death and ESRD, adjusting for demographics, comorbidity, and kidney function (estimated glomerular filtration rate [eGFR] and urine protein-to-creatinine ratio [PCR]).ResultsThere were a total of 708 ESRD events and 650 deaths events over mean (SD) follow-up periods of 4.9 (2.9) years and 6.5 (2.5) years, respectively. Lower VDMR was associated with increased risk of ESRD prior to adjusting for kidney function (hazard ratio [HR], 1.80 per 20 pg/ng lower VDMR; 95% confidence interval [CI], 1.56–2.08), but not with adjustment for kidney function (HR, 0.94 per 20 pg/ng; 95% CI, 0.81–1.10). Lower VDMR was associated with modestly increased mortality risk, including adjustment for kidney function (HR, 1.18 per 20 pg/ng; 95% CI, 1.02–1.36).ConclusionLower VDMR, a measure of CYP24A1-mediated vitamin D clearance, was significantly associated with all-cause mortality but not with progression to ESRD in patients with CKD.

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Section: Discussionsupporting

confidence: 91%

Vitamin D Metabolic Ratio and Risks of Death and CKD Progression

Bansal

Katz

Appel

et al. 2019

Kidney International Reports

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“…If this hypothesis were true, this could support the use of cholecalciferol in patients with kidney disease. Alternatively, it could also suggest the presence of pathways that convert 25(OH)D 3 to 1,24,25(OH) 3 D 3 independently of a 1,25(OH) 2 D 3 intermediary as suggested by Martineau et al 16 In a study of participants with moderate to severe CKD, cholecalciferol supplementation increased levels of 25(OH)D 3 substantially, but the change in 24,25(OH) 2 D 3 was more than proportional to the increase in 25(OH)D suggesting that supplementation increased delivery of 25(OH)D to CYP24A1 and/or increased CYP24A1 activity 21 . Levels of 1,25(OH) 2 D 3 did not change.…”

Section: Discussionmentioning

confidence: 84%

The metabolism of 1,25(OH)2D3 in clinical and experimental kidney disease

Turner

Rowsell

White

et al. 2022

Sci Rep

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Chronic kidney disease (CKD) results in calcitriol deficiency and altered vitamin D metabolism. The objective of this study was to assess the 24-hydroxylation-mediated metabolism of 25(OH)D3 and 1,25(OH)2D3 in a cross-sectional analysis of participants with a range of kidney function assessed by precise measured GFR (mGFR) (N = 143) and in rats with the induction and progression of experimental kidney disease. Vitamin D metabolites were assessed with LC–MS/MS. Circulating measures of 24-hydroxylation of 25(OH)D3 (24,25(OH)2D3:25(OH)D3) precisely decreased according to mGFR in humans and progressively in rats with developing CKD. In contrast, the 1,24,25(OH)3D3: 1,25(OH)2D3 vitamin D metabolite ratio increased in humans as the mGFR decreased and in rats with the induction and progression of CKD. Human participants taking cholecalciferol had higher circulating 1,24,25(OH)3D3, despite no increase of 1,25(OH)2D3. This first report of circulating 1,24,25(OH)3D3 in the setting of CKD provides novel insight into the uniquely altered vitamin D metabolism in this setting. A better understanding of the uniquely dysfunctional catabolic vitamin D profile in CKD may guide more effective treatment strategies. The potential that 24-hydroxylated products have biological activity of is an important area of future research.

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“…After full‐text examination, 36 publications were excluded for the following reasons: none‐randomized controlled trials (n = 8) (Alshayeb, Josephson, & Sprague, 2013; Block, 2011; Brandenburg & Kruger, 2014; Cozzolino et al, 2009; Donate‐Correa et al, 2014; Fish & Cunningham, 2012; Galassi et al, 2017; Hamano, 2018), RCTs conducted on participants younger than 18 years (n = 1) (Lerch et al, 2018), trials conducted on patients who did not have CKD (n = 6) (Burnett‐Bowie et al, 2012; Cheng et al, 2018; Macdonald et al, 2013; Mesinovic et al, 2019; Trummer et al, 2019; Uzum et al, 2010), non‐experimental studies (n = 1) (Saki, Ranjbar Omrani, & Koohpeyma, 2019), vitamin D supplementation was combined with other treatments (n = 2) (Wetmore, Liu, Krebill, Menard, & Quarles, 2010a; Wetmore, Liu, Krebill, Menard, & Quarles, 2010b), studies without suitable group for vitamin D administration (n = 10) (Albuquerque et al, 2018; Alshayeb et al, 2014; Batacchi et al, 2017b; Bleskestad, Bergrem, Hartmann, Godang, & Goransson, 2012; Cozzolino et al, 2014; Hansen, 2011; Hansen et al, 2011; Hansen, Rasmussen, Pedersen, Rasmussen, & Brandi, 2012; Hansen, Rasmussen, Rasmussen, Bruunsgaard, & Brandi, 2014; Sprague et al, 2015), lack of control group (n = 5) (Cancela et al, 2011; Chitalia et al, 2014; De Niet et al, 2018; Garcia‐Lopes et al, 2012; Zelnick, de Boer, Kestenbaum, Chonchol, & Kendrick, 2018), vitamin D administered via injection (n = 1) (Zhang et al, 2017), and insufficient data reported in the manuscript (n = 2) (Alvarez et al, 2013; Carvalho et al, 2017). Two additional studies were extracted during the full‐text evaluation by hand‐searching the reference lists of related articles, reviews, and meta‐analyses.…”

Section: Resultsmentioning

confidence: 99%

“…Goransson, 2012;Cozzolino et al, 2014;Hansen, 2011;Hansen et al, 2011;Hansen, Rasmussen, Pedersen, Rasmussen, & Brandi, 2012;Hansen, Rasmussen, Rasmussen, Bruunsgaard, & Brandi, 2014;Sprague et al, 2015), lack of control group (n = 5)(Cancela et al, 2011;Chitalia et al, 2014;De Niet et al, 2018;Garcia-Lopes et al, 2012;Zelnick, de Boer, Kestenbaum, Chonchol, & Kendrick, 2018), vitamin D administered via injection (n = 1)(Zhang et al, 2017), and insufficient data reported in the manuscript (n = 2)(Alvarez et al, 2013;Carvalho et al, 2017). Two additional studies were extracted during the full-text evaluation by hand-searching the reference lists of related articles, reviews, and meta-analyses.…”

mentioning

confidence: 99%

The effect of vitamin D supplementation on fibroblast growth factor‐23 in patients with chronic kidney disease: A systematic review and meta‐analysis

Karimi

Bitarafan

Mousavi

et al. 2021

Phytotherapy Research

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This is a meta-analysis of randomized controlled trials (RCTs) investigating the effects of oral vitamin D supplementation on serum fibroblast growth factor-23 (FGF23) concentrations in patients with chronic kidney disease (CKD). Manuscripts were extracted from PubMed/MEDLINE, Scopus, and ISI Web of Science through February 2020. Subgroup analyses, sensitivity analysis, and meta-regression assessments were performed. A total of eight clinical trials with nine treatment arms were included in the final analysis. The pooled results showed no significant changes in circulating FGF23 following vitamin D supplementation compared to the control group (Standardized mean difference (SMD): 0.24; 95% confidence intervals (CIs): À0.03 to 0.50, p > 0.05). Subgroup analyses found that studies which had participants with a body mass index (BMI) higher than 25 kg/m 2 , with an intervention duration shorter than 15 weeks, using phosphate binder medications, and trials that were on both patients with CKD undergoing hemodialysis and patients without hemodialysis treatment produced significant increases in FGF23 when concentration compared with the control group. This meta-analysis provides evidence that vitamin D supplementation does not have a significant effect on plasma FGF23 levels. However, further high-quality trials are required to identify the influence of oral vitamin D supplementation on FGF23 levels in patients with CKD. K E Y W O R D S chronic kidney disease, fibroblast growth factor-23, meta-analysis, vitamin D 1 | INTRODUCTION Patients with chronic kidney disease (CKD) experience a progressive and irreversible loss of renal function characterized by decreased glomerular filtration rate or increases in kidney failure biomarkers (Levin et al., 2013). Elevated fibroblast growth factor-23 (FGF23) is a common manifestation of impaired phosphate excretion in patients with CKD. High serum FGF23 concentrations are associated with

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Comparative Effects of Cholecalciferol and Calcitriol on Circulating Markers of CKD Mineral Bone Disorder

Cited by 7 publications

References 5 publications

Vitamin D Metabolic Ratio and Risks of Death and CKD Progression

Vitamin D Metabolic Ratio and Risks of Death and CKD Progression

The metabolism of 1,25(OH)2D3 in clinical and experimental kidney disease

The effect of vitamin D supplementation on fibroblast growth factor‐23 in patients with chronic kidney disease: A systematic review and meta‐analysis

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