@article {6340, title = {Estimated GFR and circulating 24,25-dihydroxyvitamin D3 concentration: a participant-level analysis of 5 cohort studies and clinical trials.}, journal = {Am J Kidney Dis}, volume = {64}, year = {2014}, month = {2014 Aug}, pages = {187-97}, abstract = {

BACKGROUND: 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.

STUDY DESIGN: Cross-sectional study.

SETTING \& PARTICIPANTS: 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).

PREDICTOR: eGFR.

OUTCOME: Circulating 24,25(OH)2D3 concentration.

MEASUREMENTS: GFR was estimated from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration equation. Vitamin D metabolites were measured by mass spectrometry.

RESULTS: 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.

LIMITATIONS: Lack of direct pharmacokinetic measurements of vitamin D catabolism.

CONCLUSIONS: Lower eGFR is associated strongly with reduced vitamin D catabolism, as measured by circulating 24,25(OH)2D3 concentration.

}, 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}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2014.02.015}, author = {de Boer, Ian H and Sachs, Michael C and Chonchol, Michel and Himmelfarb, Jonathan and Hoofnagle, Andrew N and Ix, Joachim H and Kremsdorf, Robin A and Lin, Yvonne S and Mehrotra, Rajnish and Robinson-Cohen, Cassianne and Siscovick, David S and Steffes, Michael W and Thummel, Kenneth E and Tracy, Russell P and Wang, Zhican and Kestenbaum, Bryan} } @article {6399, title = {Fibroblast growth factor-23 and incident atrial fibrillation: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS).}, journal = {Circulation}, volume = {130}, year = {2014}, month = {2014 Jul 22}, pages = {298-307}, abstract = {

BACKGROUND: Fibroblast growth factor-23 (FGF-23) is a hormone that promotes urinary phosphate excretion and regulates vitamin D metabolism. Circulating FGF-23 concentrations increase markedly in chronic kidney disease and are associated with increased risk of clinical cardiovascular events. FGF-23 may promote atrial fibrillation (AF) by inducing left ventricular hypertrophy and diastolic and left atrial dysfunction.

METHODS AND RESULTS: We tested the associations of circulating FGF-23 concentration with incident AF among 6398 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and 1350 participants in the Cardiovascular Health Study (CHS), all free of clinical cardiovascular disease at baseline. Over a median of 7.7 and 8.0 years of follow-up, we observed 291 and 229 incident AF events in MESA and CHS, respectively. In multivariable Cox proportional hazards models, each 2-fold-higher FGF-23 concentration was associated with a 41\% higher risk of incident AF in MESA (hazard ratio, 1.41; 95\% confidence interval, 1.13-1.76; P=0.003) and a 30\% higher risk of incident AF in CHS (hazard ratio, 1.30; 95\% confidence interval, 1.05-1.61; P=0.016) after adjustment for potential confounding characteristics, including kidney disease. Serum phosphate concentration was significantly associated with incident AF in MESA (hazard ratio, 1.15 per 0.5 mg/dL; 95\% confidence interval, 1.02-1.31; P=0.023) but not CHS. In MESA, an association of low estimated glomerular filtration rate with incident AF was partially attenuated by adjustment for FGF-23.

CONCLUSION: Higher circulating FGF-23 concentration is associated with incident AF and may, in part, explain the link between chronic kidney disease and AF.

}, keywords = {Aged, Aged, 80 and over, Atrial Fibrillation, Comorbidity, Ethnic Groups, Female, Fibroblast Growth Factor 3, Follow-Up Studies, Glomerular Filtration Rate, Heart Failure, Humans, Hypertrophy, Left Ventricular, Male, Middle Aged, Phosphates, Proportional Hazards Models, Renal Insufficiency, Chronic, Risk Factors, United States, Ventricular Dysfunction, Left, Ventricular Remodeling, Vitamin D}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.113.005499}, author = {Mathew, Jehu S and Sachs, Michael C and Katz, Ronit and Patton, Kristen K and Heckbert, Susan R and Hoofnagle, Andrew N and Alonso, Alvaro and Chonchol, Michel and Deo, Rajat and Ix, Joachim H and Siscovick, David S and Kestenbaum, Bryan and de Boer, Ian H} }