Title | Estimated GFR and circulating 24,25-dihydroxyvitamin D3 concentration: a participant-level analysis of 5 cohort studies and clinical trials. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | de 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 |
Journal | Am J Kidney Dis |
Volume | 64 |
Issue | 2 |
Pagination | 187-97 |
Date Published | 2014 Aug |
ISSN | 1523-6838 |
Keywords | 24,25-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> |
DOI | 10.1053/j.ajkd.2014.02.015 |
Alternate Journal | Am. J. Kidney Dis. |
PubMed ID | 24703961 |
PubMed Central ID | PMC4111986 |
Grant List | N01HC55222 / 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 |