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Changes in microparticle profiles by vitamin D receptor activation in chronic kidney disease - a randomized trial.

ABSTRACT: BACKGROUND:Microparticles (MPs) are biomarkers and mediators of disease through their expression of surface receptors, reflecting activation or stress in their parent cells. Endothelial markers, ICAM-1 and VCAM-1, are implicated in atherosclerosis and associated with cardiovascular risk. Chronic kidney disease (CKD) patients have endothelial dysfunction and high levels of endothelial derived MPs. Vitamin D treatment has been reported to ameliorate endothelial function in CKD patients. We aimed to examine cell specific MP profiles and concentrations of MPs expressing the atherosclerotic markers ICAM-1 and VCAM-1 after treatment with paricalcitol in patients with CKD stage 3-4. METHODS:Sub-study of the previously reported SOLID trial where 36 patients were randomly assigned to placebo, 1 or 2??g paricalcitol, for 12?weeks. MPs were measured by flow cytometry after labelling with antibodies against endothelial (CD62E), platelet (CD62P, CD41, CD154) leukocyte (CD45) and vascular (CD54, CD106) markers. RESULTS:Patients had a mean age of 65?years with a mean eGFR of 40?mL/min/1.73m2. Concentrations of ICAM-1 positive MPs were significantly reduced by treatment (repeated measures ANOVA p?=?0.04). Repeated measures MANOVA of concentrations of endothelial, platelet and leukocyte MPs showed sustained levels in the 2??g treatment group (p?=?0.85) but a decline in the 1??g (p?=?0.04) and placebo groups (p?=?0.005). CONCLUSIONS:Treatment with paricalcitol reduces concentrations of ICAM-1 positive MPs. This is accompanied by sustained concentrations of all cell specific MPs in the 2??g group, and decreasing concentrations in the other groups, possibly due to a more healthy and reactive endothelium with paricalcitol treatment.

SUBMITTER: Lundwall K

PROVIDER: S-EPMC6670162 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Changes in microparticle profiles by vitamin D receptor activation in chronic kidney disease - a randomized trial.

Lundwall Kristina K Mörtberg Josefin J Mobarrez Fariborz F Jacobson Stefan H SH Jörneskog Gun G Spaak Jonas J

BMC nephrology 20190801 1

<h4>Background</h4>Microparticles (MPs) are biomarkers and mediators of disease through their expression of surface receptors, reflecting activation or stress in their parent cells. Endothelial markers, ICAM-1 and VCAM-1, are implicated in atherosclerosis and associated with cardiovascular risk. Chronic kidney disease (CKD) patients have endothelial dysfunction and high levels of endothelial derived MPs. Vitamin D treatment has been reported to ameliorate endothelial function in CKD patients. We ...[more]

PMID: 31370809

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Project description:ImportanceDespite epidemiological and preclinical evidence suggesting that vitamin D and calcium inhibit colorectal carcinogenesis, daily supplementation with these nutrients for 3 to 5 years was not found to significantly reduce the risk of recurrent colorectal adenomas in a recent randomized clinical trial.ObjectiveTo investigate whether common variants in 7 vitamin D and calcium pathway genes (VDR, GC, DHCR7, CYP2R1, CYP27B1, CYP24A1, and CASR) modify the effects of vitamin D3 or calcium supplementation on colorectal adenoma recurrence.Design, setting, and participantsWe examined 41 candidate single-nucleotide polymorphisms (SNPs) in 2259 participants in a randomized, double-blind, placebo-controlled trial conducted at 11 clinical centers in the United States. Eligibility criteria included a recently diagnosed adenoma and no remaining colorectal polyps after complete colonoscopy. The study's treatment phase ended on August 31, 2013, and the analysis for the present study took place from July 28, 2014, to October 19, 2016.InterventionsDaily oral supplementation with vitamin D3 (1000 IU) or calcium carbonate (1200 mg elemental calcium) or both or neither.Main outcomes and measuresThe outcomes assessed were the occurrence of 1 or more adenomas or advanced adenomas (estimated diameter, ≥1 cm; or with villous histologic findings, high-grade dysplasia, or cancer) during follow-up. Treatment effects and genotype associations and interactions were estimated as adjusted risk ratios (RRs) and 95% confidence intervals (CIs). The effective number of independent SNPs was calculated to correct for multiple testing.ResultsAmong the 2259 participants randomized, 1702 were non-Hispanic whites who completed the trial and had genotype data for analysis (1101 men; mean [SD] age 58.1 [6.8] years). The effect of vitamin D3 supplementation on advanced adenomas, but not on adenoma risk overall, significantly varied according to genotype at 2 VDR SNPs (rs7968585 and rs731236) in linkage disequilibrium (D' = 0.98; r2 = 0.6). For rs7968585, among individuals with the AA genotype (26%), vitamin D3 supplementation reduced risk by 64% (RR, 0.36; 95% CI, 0.19-0.69; P = .002; absolute risk decreased from 14.4% to 5.1%). Among individuals with 1 or 2 G alleles (74%), vitamin D3 supplementation increased risk by 41% (RR, 1.41; 95% CI, 0.99-2.00; P = .05; absolute risk increased from 7.7% to 11.1%; P < .001 for interaction). There were no significant interactions of genotypes with calcium supplementation.Conclusions and relevanceOur findings suggest that benefits from vitamin D3 supplementation for the prevention of advanced colorectal adenomas may vary according to vitamin D receptor genotype.Trial registrationclinicaltrials.gov Identifier: NCT00153816.

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Changes in microparticle profiles by vitamin D receptor activation in chronic kidney disease - a randomized trial.

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Changes in microparticle profiles by vitamin D receptor activation in chronic kidney disease - a randomized trial.

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