Functional vitamin K status and risk of incident chronic kidney disease and microalbuminuria: a prospective general population-based cohort study

Dion Groothof*, Adrian Post, Camilo G Sotomayor, Charlotte A Keyzer, Jose L Flores-Guerero, Eelko Hak, Jens H J Bos, Leon J Schurgers, Gerjan J Navis, Reinold O B Gans, Coby Eelderink, Martin H de Borst, Stephan J L Bakker, Ineke J Riphagen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Web of Science)


BACKGROUND: Circulating desphospho-uncarboxylated matrix γ-carboxyglutamate (Gla) protein (dp-ucMGP), a marker of vitamin K status, is associated with renal function and may serve as a potentially modifiable risk factor for incident chronic kidney disease (CKD). We aimed to assess the association between circulating dp-ucMGP and incident CKD.

METHODS: We included 3969 participants with a mean age of 52.3 ± 11.6 years, of whom 48.0% were male, enrolled in the general population-based Prevention of REnal and Vascular ENd-stage Disease study. Study outcomes were incident CKD, defined as either development of an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or microalbuminuria. Associations of dp-ucMGP with these outcomes were quantified using Cox proportional hazards models and were adjusted for potential confounders.

RESULTS: Median plasma dp-ucMGP was 363 [interquartile range (IQR) 219-532] pmol/L and mean serum creatinine- and serum cystatin C-based eGFR (eGFRSCr-SCys) was 95.4 ± 21.8 mL/min/1.73 m2. During 7.1 years of follow-up, 205 (5.4%) participants developed incident CKD and 303 (8.4%) developed microalbuminuria. For every doubling of plasma dp-ucMGP, hazard ratios for the development of incident CKD and microalbuminuria were 1.85 [95% confidence interval (CI) 1.59-2.16; P < 0.001] and 1.19 (95% CI 1.07-1.32; P = 0.001), respectively. These associations lost significance after adjustment for baseline eGFRSCr-SCys [0.99 (95% CI 0.88-1.12; P = 0.86)] and baseline age [1.03 (95% CI 0.94-1.14; P = 0.50)], respectively.

CONCLUSIONS: The associations of plasma dp-ucMGP with incident CKD and microalbuminuria were driven by the respective baseline effects of renal function and age.

Original languageEnglish
Pages (from-to)2290-2299
Number of pages10
JournalNephrology Dialysis Transplantation
Issue number12
Early online date13 Dec 2020
Publication statusPublished - Dec 2021


  • chronic kidney disease
  • matrix Gla protein
  • micro-albuminuria
  • renal deterioration
  • vitamin K

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