Chronic kidney disease is characterized, in part, as a state of decreased production of 1,25-dihydroxyvitamin D (1,25(OH)2D); however, this paradigm overlooks the role of vitamin D catabolism. We developed a mass spectrometric assay to quantify serum concentration of 24,25-dihydroxyvitamin D (24,25(OH)2D), the first metabolic product of 25-hydroxyvitamin D (25(OH)D) by CYP24A1, and determined its clinical correlates and associated outcomes among 278 participants with chronic kidney disease in the Seattle Kidney Study. For eGFRs of 60 or more, 45–59, 30–44, 15–29, and under 15 ml/min/1.73m2, the mean serum 24,25(OH)2D concentrations significantly trended lower from 3.6, 3.2, 2.6, 2.6, to 1.7 ng/ml, respectively. Non-Hispanic Black race, diabetes, albuminuria, and lower serum bicarbonate were also independently and significantly associated with lower 24,25(OH)2D concentrations. The 24,25(OH)2D concentration was more strongly correlated with that of parathyroid hormone than was 25(OH)D or 1,25(OH)2D. A 24,25(OH)2D concentration below the median was associated with increased risk of mortality in unadjusted analysis, but this was attenuated with adjustment for potential confounding variables. Thus, chronic kidney disease is a state of stagnant vitamin D metabolism characterized by decreases in both 1,25(OH)2D production and vitamin D catabolism.

Vitamin D metabolism consists of both production and catabolism, which are enzymatically driven and highly regulated. Renal vitamin D metabolism requires filtration and tubular reabsorption of 25-hydroxyvitamin D and is regulated by parathyroid hormone, fibroblast growth factor-23, and 1,25-dihydroxyvitamin D. In CKD, renal production of1,25-dihydroxyvitamin D from 25-hydroxyvitamin D is reduced. In addition, pharmacokinetic studies and epidemiologic studies of 24,25-dihydroxyvitamin D, the most abundant product of 25-hydroxyvitamin D catabolism by CYP24A1, suggest that vitamin D catabolism is also reduced. New insights into the mechanisms and regulation of vitamin D metabolism may lead to novel approaches to assess and treat impaired vitamin D metabolism in CKD.

Objective High circulating concentrations of parathyroid hormone (PTH) have been associated with increased risks of hypertension, left ventricular hypertrophy, congestive heart failure, and cardiovascular mortality. Impaired arterial function is a potential mechanism for these associations. We tested whether serum PTH concentration is associated with measures of arterial function. Design Cross-sectional study. Participants 6,545 persons without clinical cardiovascular disease participating in the community-based Multi-Ethnic Study of Atherosclerosis. Measurements Brachial artery flow-mediated dilation as well as aortic pulse pressure and arterial pulse parameters derived from Windkessel modeling of the radial pressure waveform. Results Higher serum PTH concentration was associated with lower brachial artery flow-mediated dilation (mean difference −0.09% per 10 pg/mL PTH), higher aortic pulse pressure (0.53 mmHg per 10 pg/mL), and reduced Windkessel capacitive index C1 (large artery elasticity, −0.12 ml/mmHg X 10 per 10 pg/mL), adjusting for potential confounding variables (all p-values ≤ 0.001). These relationships were independent of serum calcium concentration, serum 25-hydroxyvitamin D concentration, and estimated glomerular filtration rate and were consistent across relevant participant subgroups. Associations of PTH with aortic pulse pressure and capacitive index C1 were attenuated after adjustment for blood pressure. Serum PTH concentration was not associated with the oscillatory index C2 (small artery elasticity). Conclusions Higher serum PTH concentration was associated with impaired endothelial function, increased aortic pulse pressure, and decreased capacitive index C1 in a large, diverse, community-based population. These relationships may help explain previously observed associations of elevated PTH with cardiovascular disease.

Background: The association of serum bilirubin concentrations with kidney function and albuminuria has not been established in the US general population. Methods: We performed a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) [2001][2002][2003][2004][2005][2006] and examined the associations of serum total bilirubin concentrations with estimated glomerular filtration rate (eGFR) and albuminuria in a nationally representative sample of 13,184 adults aged 20 years or older. eGFR was estimated using the abbreviated Modification of Diet in Renal Disease equation. Urinary albumin excretion was measured using the albumin/creatinine ratio. Results: An eGFR -60 mL/min/1.73 m 2 and urinary albumin/creatinine ratio G30 mg/g were present in 8.1% (ns1072) and 10.6% (ns1402) of participants, respectively. A total of 427 (3.2%) individuals had a