Phylloquinone and Vitamin D Status: Associations with Incident Chronic Kidney Disease in the Framingham Offspring Cohort

Abstract

Background: 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. Methods: We analyzed 1,442 Framingham Heart Study participants (mean age 58 years; 50.5% women), free of CKD (eGFR <60 ml/min/1.73 m²), with a mean follow-up of 7.8 years in 2005–2008. Incident albuminuria was defined using sex-specific cut-offs of urine albumin-to-creatinine ratio (≥17 mg/g men and ≥25 mg/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. Results: Participants in the highest phylloquinone quartile (≥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. Conclusions: 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.