biostudies-literatureHsu SNational Center for Advancing Translational SciencesNorthwest Kidney CentersNCATS NIH HHSNIDDK NIH HHSNHLBI NIH HHSNational Institutes of HealthNIDDKNIGMS NIH HHS106047https://www.ebi.ac.uk/biostudies/studies/S-EPMC8837693biostudies-literatureUnknown217The formation of 24,25-dihydroxyvitamin D (24,25(OH)₂D) from 25-hydroxyvitamin D (25(OH)D) is the primary mechanism for the metabolic clearance of 25(OH)D, and is regulated by tissue-level vitamin D activity. The ratio of 24,25(OH)₂D₃ to 25(OH)D₃ in blood (vitamin D metabolite ratio, VDMR) is postulated to be a marker of 25(OH)D₃ clearance, however this has never been tested. We measured baseline 24,25(OH)₂D₃ and 25(OH)D₃ concentrations in 87 participants by liquid chromatography-tandem mass spectrometry. Following an infusion of deuterated 25(OH)D₃, blood samples for each participant were collected over 56 days and analyzed for deuterated vitamin D metabolites. 25(OH)D₃ clearance and the deuterated metabolite-to-parent AUC ratio (ratio of the AUC of deuterated 24,25(OH)₂D₃ to that of deuterated 25(OH)D₃) were calculated. We compared the VDMR with these two measures using correlation coefficients and linear regression. Participants had a mean age of 64 ± 11years, 41 % were female, 30 % were self-described Black, 28 % had non-dialysis chronic kidney disease (CKD) and 23 % had kidney failure treated with hemodialysis. The VDMR was strongly correlated with 25(OH)D₃ clearance and the deuterated metabolite-to-parent AUC ratio (r = 0.51 and 0.76, respectively). Adjusting for 25(OH)D₃ clearance or the deuterated metabolite-to-parent AUC ratio in addition to clinical covariates, lower VDMR was observed in participants with CKD and kidney failure than in healthy controls; in Black than White participants; and in those with lower serum albumin. Our findings validate the VDMR as a measure of 25(OH)D₃ clearance. This relationship was biased by characteristics including race and kidney disease, which warrant consideration in studies assessing the VDMR.The Journal of steroid biochemistry and molecular biologyValidation of the 24,25-dihydroxyvitamin D₃ to 25-hydroxyvitamin D₃ ratio as a biomarker of 25-hydroxyvitamin D₃ clearance.PMC88376932T32DK007467T32 HL007028R01GM63666F32 DK128986R01DK099199-S11F32DK128986-01P30 DK040561R01 DK099199T32 DK007467P30 DK035816R01 GM063666UL1 TR002319Hsu SLin YSHoofnagle ANBest CMde Boer IHThummel KEKestenbaum BRZelnick LRfalseValidation of the 24,25-dihydroxyvitamin D₃ to 25-hydroxyvitamin D₃ ratio as a biomarker of 25-hydroxyvitamin D₃ clearance.The formation of 24,25-dihydroxyvitamin D (24,25(OH)₂D) from 25-hydroxyvitamin D (25(OH)D) is the primary mechanism for the metabolic clearance of 25(OH)D, and is regulated by tissue-level vitamin D activity. The ratio of 24,25(OH)₂D₃ to 25(OH)D₃ in blood (vitamin D metabolite ratio, VDMR) is postulated to be a marker of 25(OH)D₃ clearance, however this has never been tested. We measured baseline 24,25(OH)₂D₃ and 25(OH)D₃ concentrations in 87 participants by liquid chromatography-tandem mass spectrometry. Following an infusion of deuterated 25(OH)D₃, blood samples for each participant were collected over 56 days and analyzed for deuterated vitamin D metabolites. 25(OH)D₃ clearance and the deuterated metabolite-to-parent AUC ratio (ratio of the AUC of deuterated 24,25(OH)₂D₃ to that of deuterated 25(OH)D₃) were calculated. We compared the VDMR with these two measures using correlation coefficients and linear regression. Participants had a mean age of 64 ± 11years, 41 % were female, 30 % were self-described Black, 28 % had non-dialysis chronic kidney disease (CKD) and 23 % had kidney failure treated with hemodialysis. The VDMR was strongly correlated with 25(OH)D₃ clearance and the deuterated metabolite-to-parent AUC ratio (r = 0.51 and 0.76, respectively). Adjusting for 25(OH)D₃ clearance or the deuterated metabolite-to-parent AUC ratio in addition to clinical covariates, lower VDMR was observed in participants with CKD and kidney failure than in healthy controls; in Black than White participants; and in those with lower serum albumin. Our findings validate the VDMR as a measure of 25(OH)D₃ clearance. This relationship was biased by characteristics including race and kidney disease, which warrant consideration in studies assessing the VDMR.2022-01-01T00:00:00Z2022 Mar2024-11-20T08:01:45.337Z2024-11-20T08:01:45.337ZS-EPMC88376933495401710.1016/j.jsbmb.2021.106047