title: Vitamin K status and mortality after kidney transplantation: a cohort study.
abstract: BACKGROUND
  Vitamin K modulates calcification by activating calcification inhibitors such as matrix Gla protein (MGP). In kidney transplant recipients, vitamin K insufficiency is common, but implications for long-term outcomes are unclear.
  
  
  METHODS
  Single-center observational study with a longitudinal design.
  
  
  METHODS
  518 stable kidney transplant recipients; 56% men; mean age, 51±12 (SD) years; and a median of 6 (IQR, 3-12) years after kidney transplantation.
  
  
  METHODS
  Plasma desphosphorylated-uncarboxylated MGP (dp-ucMGP) levels, reflecting vitamin K status.
  
  
  RESULTS
  All-cause mortality and transplant failure.
  
  
  RESULTS
  At inclusion, median dp-ucMGP level was 1,038 (IQR, 733-1,536) pmol/L, with 473 (91%) patients having vitamin K insufficiency (defined as dp-ucMGP>500pmol/L). During a median follow-up of 9.8 (IQR, 8.5-10.2) years, 152 (29%) patients died and 54 (10%) developed transplant failure. Patients in the highest quartile of dp-ucMGP were at considerably higher mortality risk compared with patients in the lowest quartile (HR, 3.10; 95% CI, 1.87-5.12; P for trend<0.001; P for quartile 1 [Q1] vs Q4<0.001). After adjustment for potential confounders, including kidney function and exclusion of patients treated with a vitamin K antagonist, this association remained significant. Patients in the highest quartile also were at higher risk of developing transplant failure (HR, 2.61; 95% CI, 1.22-5.57; P for trend=0.004; P for Q1 vs Q4=0.01), but this association was lost after adjustment for baseline kidney function (HR, 1.20; 95% CI, 0.52-2.75; P for trend=0.6; P for Q1 vs Q4=0.7).
  
  
  CONCLUSIONS
  Although MGP exists as various species, only dp-ucMGP was measured. No data were available for vascular calcification as an intermediate end point.
  
  
  CONCLUSIONS
  Vitamin K insufficiency, that is, a high circulating level of dp-ucMGP, is highly prevalent in stable kidney transplant recipients and is associated independently with increased risk of mortality. Future studies should address whether vitamin K supplementation may lead to improved outcomes after kidney transplantation.
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Keyzer
authors.affiliation: VitaK, Maastricht University, Maastricht, the Netherlands.
authors.forename: Cees
authors.initials: C
authors.lastname: Vermeer
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Top Institute Food and Nutrition, Wageningen, the Netherlands.
authors.forename: Michel M
authors.initials: MM
authors.lastname: Joosten
authors.affiliation: VitaK, Maastricht University, Maastricht, the Netherlands.
authors.forename: Marjo H J
authors.initials: MH
authors.lastname: Knapen
authors.affiliation: VitaK, Maastricht University, Maastricht, the Netherlands.
authors.forename: Nadja E A
authors.initials: NE
authors.lastname: Drummen
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Top Institute Food and Nutrition, Wageningen, the Netherlands.
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address: m.h.de.borst@umcg.nl.
authors.forename: Martin H
authors.initials: MH
authors.lastname: de Borst
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002135:Calcium-Binding Proteins / Q000097:blood; D015331:Cohort Studies; D016326:Extracellular Matrix Proteins / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016030:Kidney Transplantation / Q000401:mortality* / Q000639:trends; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D014812:Vitamin K / Q000097:blood*; D014813:Vitamin K Deficiency / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D000097568:Matrix Gla Protein
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D014812:Vitamin K; D000097568:Matrix Gla Protein
keywords: Desphosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP); cardiovascular disease; graft failure; kidney transplantation; mortality; renal transplant recipients; vascular calcification; vitamin K; vitamin K insufficiency