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Estimated GFR and circulating 24,25-dihydroxyvitamin D3 concentration: a participant-level analysis of 5 cohort studies and clinical trials.

TitleEstimated GFR and circulating 24,25-dihydroxyvitamin D3 concentration: a participant-level analysis of 5 cohort studies and clinical trials.
Publication TypeJournal Article
Year of Publication2014
Authorsde Boer, IH, Sachs, MC, Chonchol, M, Himmelfarb, J, Hoofnagle, AN, Ix, JH, Kremsdorf, RA, Lin, YS, Mehrotra, R, Robinson-Cohen, C, Siscovick, DS, Steffes, MW, Thummel, KE, Tracy, RP, Wang, Z, Kestenbaum, B
JournalAm J Kidney Dis
Volume64
Issue2
Pagination187-97
Date Published2014 Aug
ISSN1523-6838
Keywords24,25-Dihydroxyvitamin D 3, Adult, Aged, Aged, 80 and over, Biomarkers, Cohort Studies, Cross-Sectional Studies, Diabetes Mellitus, Female, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Male, Middle Aged, Observational Studies as Topic, Randomized Controlled Trials as Topic, Young Adult
Abstract<p><b>BACKGROUND: </b>Decreased glomerular filtration rate (GFR) leads to reduced production of 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3 (25[OH]D3). Effects of low GFR on vitamin D catabolism are less well understood. We tested associations of estimated GFR (eGFR) with the circulating concentration of 24,25-dihydroxyvitamin D3 (24,25[OH]2D3), the most abundant product of 25(OH)D3 catabolism, across populations with a wide range of GFRs.</p><p><b>STUDY DESIGN: </b>Cross-sectional study.</p><p><b>SETTING & PARTICIPANTS: </b>9,596 participants in 5 cohort studies and clinical trials: the Diabetes Control and Complications Trial (N=1,193), Multi-Ethnic Study of Atherosclerosis (N=6,470), Cardiovascular Health Study (N=932), Seattle Kidney Study (N=289), and Hemodialysis Study (N=712).</p><p><b>PREDICTOR: </b>eGFR.</p><p><b>OUTCOME: </b>Circulating 24,25(OH)2D3 concentration.</p><p><b>MEASUREMENTS: </b>GFR was estimated from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration equation. Vitamin D metabolites were measured by mass spectrometry.</p><p><b>RESULTS: </b>Circulating 24,25(OH)2D3 concentration was correlated with circulating 25(OH)D3 concentration (Pearson r range, 0.64-0.88). This correlation was weaker with lower eGFRs. Moreover, the increment in 24,25(OH)2D3 concentration associated with higher 25(OH)D3 concentration (slope) was lower with lower eGFRs: 2.06 (95% CI, 2.01-2.10), 1.77 (95% CI, 1.74-1.81), 1.55 (95% CI, 1.48-1.62), 1.17 (95% CI, 1.05-1.29), 0.92 (95% CI, 0.74-1.10), 0.61 (95% CI, 0.22-1.00), and 0.37 (95% CI, 0.35-0.39) ng/mL of 24,25(OH)2D3 per 10 ng/mL of 25(OH)D3 for eGFRs≥90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m2 and end-stage renal disease treated with hemodialysis, respectively. As a result, at a 25(OH)D3 concentration of 20 ng/mL, mean 24,25(OH)2D3 concentrations were 2.92 (95% CI, 2.87-2.96), 2.68 (95% CI, 2.64-2.72), 2.35 (95% CI, 2.26-2.45), 1.92 (95% CI, 1.74-2.10), 1.69 (95% CI, 1.43-1.95), 1.14 (95% CI, 0.62-1.66), and 1.04 (95% CI,1.02-1.07) ng/mL for each category, respectively. This interaction was independent of other relevant clinical characteristics. Race, diabetes, urine albumin excretion, and circulating parathyroid hormone and fibroblast growth factor 23 concentrations more modestly modified the association of 24,25(OH)2D3 with 25(OH)D3.</p><p><b>LIMITATIONS: </b>Lack of direct pharmacokinetic measurements of vitamin D catabolism.</p><p><b>CONCLUSIONS: </b>Lower eGFR is associated strongly with reduced vitamin D catabolism, as measured by circulating 24,25(OH)2D3 concentration.</p>
DOI10.1053/j.ajkd.2014.02.015
Alternate JournalAm. J. Kidney Dis.
PubMed ID24703961
PubMed Central IDPMC4111986
Grant ListN01HC55222 / HC / NHLBI NIH HHS / United States
R01 DK087726 / DK / NIDDK NIH HHS / United States
R01 DK088762 / DK / NIDDK NIH HHS / United States
R01HL080295 / HL / NHLBI NIH HHS / United States
RC4DK090766 / DK / NIDDK NIH HHS / United States
R01 DK081473 / DK / NIDDK NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
UL1-RR-025005 / RR / NCRR NIH HHS / United States
R01DK081473 / DK / NIDDK NIH HHS / United States
R01HL096875 / HL / NHLBI NIH HHS / United States
N01HC95159 / HC / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
UL1-RR-024156 / RR / NCRR NIH HHS / United States
R01 HL096851 / HL / NHLBI NIH HHS / United States
UL1 RR024156 / RR / NCRR NIH HHS / United States
R01DK088762 / DK / NIDDK NIH HHS / United States
R01 GM063666 / GM / NIGMS NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
R01HL102214 / HL / NHLBI NIH HHS / United States
N01HC95169 / HC / NHLBI NIH HHS / United States
N01HC85079 / HC / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
R01 HL102214 / HL / NHLBI NIH HHS / United States
RC4 DK090766 / DK / NIDDK NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
N01HC85086 / HC / NHLBI NIH HHS / United States
R01 HL080295 / HL / NHLBI NIH HHS / United States
R01DK087726 / DK / NIDDK NIH HHS / United States
P30 DK035816 / DK / NIDDK NIH HHS / United States
HHSN268200800007C / / PHS HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
HHSN268201200036C / / PHS HHS / United States
N01HC85083 / HC / NHLBI NIH HHS / United States
T32 DK007662 / DK / NIDDK NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
R01HL096851 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
AG023629 / AG / NIA NIH HHS / United States
R01 HL096875 / HL / NHLBI NIH HHS / United States
R56 AG023629 / AG / NIA NIH HHS / United States
P30 DK017047 / DK / NIDDK NIH HHS / United States