The serum 24,25-dihydroxyvitamin D concentration, a marker of vitamin D catabolism, is reduced in chronic kidney disease.
Chronic kidney disease is characterized, in part, as a state of decreased production of 1,25-dihydroxyvitamin D (1,25(OH)(2)D); 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)(2)D), 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 per 1.73 m(2), the mean serum 24,25(OH)(2)D 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)(2)D concentrations. The 24,25(OH)(2)D concentration was more strongly correlated with that of parathyroid hormone than was 25(OH)D or 1,25(OH)(2)D. A 24,25(OH)(2)D 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)(2)D production and vitamin D catabolism.
Department of Medicine, Division of Nephrology and Kidney Research Institute, University of Washington, Seattle, WA 98104, USA.
Cortney R
CR
Bosworth
Gregory
G
Levin
Cassianne
C
Robinson-Cohen
Andrew N
AN
Hoofnagle
John
J
Ruzinski
Bessie
B
Young
Stephen M
SM
Schwartz
Jonathan
J
Himmelfarb
Bryan
B
Kestenbaum
Ian H
IH
de Boer
D001741:Black or African American; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015897:Comorbidity; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000208:ethnology / Q000401:mortality; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D015999:Multivariate Analysis; D010281:Parathyroid Hormone / Q000097:blood; D011379:Prognosis; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000208:ethnology / Q000401:mortality / Q000503:physiopathology; D018570:Risk Assessment; D012307:Risk Factors; D013250:Steroid Hydroxylases / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood*; D065668:Vitamin D3 24-Hydroxylase; D014861:Washington / Q000453:epidemiology
D015415:Biomarkers; C470125:PTH protein, human; D010281:Parathyroid Hormone; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase