04205nas a2200529 4500008004100000022001400041245014500055210006900200260001300269300001100282490000700293520262400300653003102924653001002955653000902965653002202974653001502996653001903011653002803030653002203058653001103080653003103091653001103122653002803133653000903161653001603170653003503186653004203221653001603263100002003279700002203299700002103321700002503342700002503367700001903392700002403411700001903435700002203454700003003476700002403506700002403530700002403554700002203578700001703600700002203617856003603639 2014 eng d a1523-683800aEstimated GFR and circulating 24,25-dihydroxyvitamin D3 concentration: a participant-level analysis of 5 cohort studies and clinical trials.0 aEstimated GFR and circulating 2425dihydroxyvitamin D3 concentrat c2014 Aug a187-970 v643 a

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.

10a24,25-Dihydroxyvitamin D 310aAdult10aAged10aAged, 80 and over10aBiomarkers10aCohort Studies10aCross-Sectional Studies10aDiabetes Mellitus10aFemale10aGlomerular Filtration Rate10aHumans10aKidney Failure, Chronic10aMale10aMiddle Aged10aObservational Studies as Topic10aRandomized Controlled Trials as Topic10aYoung Adult1 ade Boer, Ian, H1 aSachs, Michael, C1 aChonchol, Michel1 aHimmelfarb, Jonathan1 aHoofnagle, Andrew, N1 aIx, Joachim, H1 aKremsdorf, Robin, A1 aLin, Yvonne, S1 aMehrotra, Rajnish1 aRobinson-Cohen, Cassianne1 aSiscovick, David, S1 aSteffes, Michael, W1 aThummel, Kenneth, E1 aTracy, Russell, P1 aWang, Zhican1 aKestenbaum, Bryan uhttps://chs-nhlbi.org/node/634003262nas a2200313 4500008004100000022001400041245020200055210006900257260001600326300001400342490000700356520223900363100001802602700002202620700001902642700002402661700002002685700001502705700001602720700002202736700001702758700003002775700002002805700002402825700002202849700001802871700002302889856003602912 2017 eng d a1555-905X00aeGFR and Albuminuria in Relation to Risk of Incident Atrial Fibrillation: A Meta-Analysis of the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study.0 aeGFR and Albuminuria in Relation to Risk of Incident Atrial Fibr c2017 Sep 07 a1386-13980 v123 a

BACKGROUND AND OBJECTIVES: The incidence of atrial fibrillation is high in ESRD, but limited data are available on the incidence of atrial fibrillation across a broad range of kidney function. Thus, we examined the association of eGFR and urine albumin-to-creatinine ratio with risk of incident atrial fibrillation.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We meta-analyzed three prospective cohorts: the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study. Cox regression models were performed examining the association of eGFR and urine albumin-to-creatinine ratio with incident atrial fibrillation adjusting for demographics and comorbidity. In additional analyses, we adjusted for measures of subclinical cardiovascular disease (by electrocardiogram and cardiac imaging) and interim heart failure and myocardial infarction events.

RESULTS: In the meta-analyzed study population of 16,769 participants without prevalent atrial fibrillation, across categories of decreasing eGFR (eGFR>90 [reference], 60-89, 45-59, 30-44, and <30 ml/min per 1.73 m(2)), there was a stepwise increase in the adjusted risk of incident atrial fibrillation: hazard ratios (95% confidence intervals) were 1.00, 1.09 (0.97 to 1.24), 1.17 (1.00 to 1.38), 1.59 (1.28 to 1.98), and 2.03 (1.40 to 2.96), respectively. There was a stepwise increase in the adjusted risk of incident atrial fibrillation across categories of increasing urine albumin-to-creatinine ratio (urine albumin-to-creatinine ratio <15 [reference], 15-29, 30-299, and ≥300 mg/g): hazard ratios (95% confidence intervals) were 1.00, 1.04 (0.83 to 1.30), 1.47 (1.20 to 1.79), and 1.76 (1.18 to 2.62), respectively. The associations were consistent after adjustment for subclinical cardiovascular disease measures and interim heart failure and myocardial infarction events.

CONCLUSIONS: In this meta-analysis of three cohorts, reduced eGFR and elevated urine albumin-to-creatinine ratio were significantly associated with greater risk of incident atrial fibrillation, highlighting the need for further studies to understand mechanisms linking kidney disease with atrial fibrillation.

1 aBansal, Nisha1 aZelnick, Leila, R1 aAlonso, Alvaro1 aBenjamin, Emelia, J1 ade Boer, Ian, H1 aDeo, Rajat1 aKatz, Ronit1 aKestenbaum, Bryan1 aMathew, Jehu1 aRobinson-Cohen, Cassianne1 aSarnak, Mark, J1 aShlipak, Michael, G1 aSotoodehnia, Nona1 aYoung, Bessie1 aHeckbert, Susan, R uhttps://chs-nhlbi.org/node/7464