Submitted to: The American Journal of Nephrology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 4/23/2012
Publication Date: 7/1/2012
Citation: O'Seaghdha, C., Hwang, S., Holden, R., Booth, S., Fox, C. 2012. Vitamin K and vitamin D status: associations with incident chronic kidney disease in the Framingham Offspring Cohort. The American Journal of Nephrology. 36:68-77. Interpretive Summary: Cardiovascular risk factors are associated with the development of chronic kidney disease. Evidence suggests that deficiencies of vitamins D and K may adversely affect the cardiovascular system, but data on the roles of these two vitamins in development of chronic kidney disease are lacking. We hypothesized that deficiencies of vitamins D and K may be associated with the development of chronic kidney disease among members of the general population. We analyzed vitamin D and vitamin K status in 1442 men and women participating in the Framingham Heart Study who were free of kidney disease, and monitored them for an average follow-up time of 7.8 years. The study results show that vitamin D blood levels were not related to risk of kidney disease. High baseline blood levels of vitamin K were unexpectedly associated with an increased risk of developing chronic kidney disease. High blood levels of vitamin K may be a marker for another unmeasured risk factor for kidney disease and requires further study. Furthermore, confirmation in other community-base cohorts is necessary to determine if this is a spurious finding given the unexpected nature of these results.
Technical Abstract: Cardiovascular risk factors are associated with the development of chronic kidney disease (CKD), and CKD and vascular disease are etiologically linked. Evidence suggests deficiencies of vitamins D and K may adversely affect the cardiovascular system, but data from longitudinal studies are lacking. We hypothesized that deficiencies of vitamins D and K may be associated with incident CKD and/or incident albuminuria amongst members of the general population. We analyzed 1442 Framingham Heart Study participants (mean age 58 years; 50.5% women), free of CKD (eGFR<60 ml/min/1.732), with a mean follow-up of 7.8 years in 2005-2008. Incident albuminuria was defined using sex-specific cutoffs of urine albumin-to-creatinine ratio (=17mg/g men and =25mg/g women). Baseline log plasma phylloquinone (vitamin K1) and 25(OH)D levels, analyzed as continuous variables and by quartile, were related to risk of incident CKD (n=108) and incident albuminuria (n=106) using logistic regression models adjusted for standard risk factors. Participants in the highest phylloquinone quartile (greater than or equal to 1.78 nmol/L) had an increased risk of CKD (multivariable-adjusted OR Q4 vs. Q1 2.39; p=0.006) and albuminuria at follow-up (multivariable-adjusted OR Q4 vs. Q1 1.95; p=0.05), whereas no association was observed with continuous phylloquinone levels for either endpoint. Deficiency of 25(OH)D was not associated with incident CKD or albuminuria in either analysis. Contrary to our hypothesis, higher plasma phylloquinone levels are associated with an increased risk of incident CKD. Whether plasma phylloquinone is a marker for another unmeasured risk factor requires further study. External validation is necessary given the unexpected nature of these results.