Home Overweight-obesity is associated with decreased vitamin K2 levels in hemodialysis patients
Article
Licensed
Unlicensed Requires Authentication

Overweight-obesity is associated with decreased vitamin K2 levels in hemodialysis patients

  • Maura Ravera , Thomas Nickolas , Mario Plebani ORCID logo , Giorgio Iervasi , Andrea Aghi , Pascale Khairallah , Maurizio Gallieni , Maria Cristina Mereu , Sandro Giannini , Stefania Sella , Martina Zaninotto , Ernesto Paoletti , Elisabetta Bussalino , Luca Di Lullo , Antonio Bellasi , Laura Cosmai , Marina Foramitti , Fabio Malberti , Maria Luisa Brandi , Serge Ferrari , Giovanni Tripepi and Maria Fusaro EMAIL logo
Published/Copyright: May 8, 2020
Become an author with De Gruyter Brill
Submit Manuscript Author Information
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 59 Issue 3

Abstract

Objectives

Obesity is an important risk factor for morbidity and mortality. Vitamin K2 is involved in the production of bone and matrix amino acid g-carboxy-glutamic acid (Gla) proteins (vitamin K-dependent proteins [VKDPs]), regulating bone and vascular calcification (VC). Bone Gla protein (BGP) is involved both in bone mineralization and VCs. We assessed the relationships between vitamin K levels and body mass index (BMI) according to the hypothesis that the impact of BMI on mortality is partly driven by low vitamin K levels.

Methods

The Vitamin K Italian (VIKI) study included 387 hemodialysis patients from 18 dialysis centers in Italy. We determined plasma levels of bone markers: vitamin K levels, VKDPs, vitamin 25(OH)D, alkaline phosphatase (ALP), parathyroid hormone (PTH), calcium (Ca), phosphorus (P) and routine biochemistry. BMI was classified into the following categories: underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 25 kg/m2), overweight (25 ≤ BMI < 30 kg/m2) and obese (BMI ≥ 30 kg/m2).

Results

45.2% of patients were overweight or obese. Stratification by BMI demonstrated lower median menaquinone-7 (MK7)/triglycerides levels in obese patients (0.42 ng/mg [0.19, 0.87], p = 0.005). BGP levels were lower in overweight and obese patients (152 mcg/L [83.2, 251] and 104 mcg/L [62.7, 230], p = <0.001). Furthermore, there was an inverse correlation between MK7/triglycerides levels and BMI (regression coefficient β = −0.159; p = 0.003). In multiple linear regression, there was an inverse relationship between BGP levels and BMI (β = − 0.119; p = 0.012).

Conclusions

These data are the first to report an inverse relationship between Vitamin K2 levels and BMI in hemodialysis patients. Further studies are needed to confirm these findings and to determine if lower levels of Vitamin K are related to greater morbidity and mortality in this at-risk population.

Keywords: BMI; hemodialysis; obesity; vitamin K
Corresponding author: Maria Fusaro, MD, PhD, National Research Council (CNR), Institute of Clinical Physiology (IFC), Pisa Via G. Moruzzi 1, 56124, Pisa, PI, Italy; and Department of Medicine, University of Padua, Via Giustiniani 2, 35128 Padova, PD, Italy

Appendix

Laboratory determination

The Laboratory in Perugia determined vitamin K components by a simple, sensitive and selective reversed-phase high-performance liquid chromatography (HPLC) method, developed for the simultaneous determination of vitamin K in human plasma. Clear and well-separated chromatographic PK and MK profiles were obtained in healthy human and uremic plasma [13].

The adjustment for triglycerides concentration is particularly relevant for the assessment of vitamin K status. Vitamin K components are all liposoluble compounds that become part of chylomicrons after absorption from the gut and as such are transported to the liver. Vitamin K1 remains partly in the liver, whereas vitamin K2 is transferred to VLDL and LDL for transport and there is a close correlation (r=0.99) between triglycerides concentrations and vitamin K1 [13].

Uremic plasma is characterized by an increased level of plasma lipids and lipoproteins, which are interfering factors to chromatography. Thus, we adopted a liquid-liquid extraction and then a solid-phase extraction of human plasma using polymeric reversed-phase cartridges, achieving good reproducibility. The vitamers were measured by an electrochemical detector after post-column reduction with platinum on alumina powder and using the MK8 form as the internal standard. Quantitative recovery was obtained in the range of 80%–96% for PK and MK vitamers. Vitamin K values were corrected according to triglycerides levels [13].

  1. Author contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Maria Fusaro, Andrea Aghi and Giovanni Tripepi. The first draft of the manuscript was written by Maura Ravera and Maria Fusaro, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: Authors state no conflict of interest.

  6. Informed consent: Informed consent was obtained from all individuals included in this study.

  7. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Research Committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

References

1. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Accessed 07 May 2019.Search in Google Scholar

2. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet 2017;390:2627–42.10.1016/S0140-6736(17)32129-3Search in Google Scholar

3. Kovesdy CP, Furth SL, Zoccali C, World Kidney Day Steering Committee. Obesity and kidney disease: hidden consequences of the epidemic. Can J Kidney Health Dis 2017;4:2054358117698669.10.1177/2054358117698669Search in Google Scholar PubMed PubMed Central

4. Beddhu S, Pappas LM, Ramkumar N, Samore M. Effects of body size and body composition on survival in hemodialysis patients. J Am Soc Nephrol 2003;14:2366–72.10.1097/01.ASN.0000083905.72794.E6Search in Google Scholar

5. Kalantar-Zadeh K, Rhee CM, Chou J, Ahmadi SF, Park J, Chen JL, et al. The obesity paradox in kidney disease: how to reconcile it with obesity management. Kidney Int Rep 2017;2:271–81.10.1016/j.ekir.2017.01.009Search in Google Scholar PubMed PubMed Central

6. Shearer MJ, Newman P. Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis. J Lipid Res 2014;55:345–62.10.1194/jlr.R045559Search in Google Scholar PubMed PubMed Central

7. Shearer MJ, Newman P. Metabolism and cell biology of vitamin K. Thromb Haemost 2008;100:530–47.10.1160/TH08-03-0147Search in Google Scholar

8. Fusaro M, Mereu MC, Aghi A, Iervasi G, Gallieni M. Vitamin K and bone. Clin Cases Miner Bone Metab 2017;14:200–6.10.11138/ccmbm/2017.14.1.200Search in Google Scholar PubMed PubMed Central

9. Fusaro M, Crepaldi G, Maggi S, Galli F, D’Angelo A, Calò L, et al. Vitamin K, bone fractures, and vascular calcifications in chronic kidney disease: an important but poorly studied relationship. J Endocrinol Invest 2011;34:317–23.10.1007/BF03347093Search in Google Scholar PubMed

10. Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C, et al. Increased bone formation in osteocalcin-deficient mice. Nature 1996;382:448–52.10.1038/382448a0Search in Google Scholar PubMed

11. Schurgers LJ, Cranenburg EC, Vermeer C. Matrix Gla-protein: the calcification inhibitor in need of vitamin K. Thromb Haemost 2008;100:593–603.10.1160/TH08-02-0087Search in Google Scholar

12. Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, et al. Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 1997;386:78–81.10.1038/386078a0Search in Google Scholar PubMed

13. Fusaro M, Noale M, Viola V, Galli F, Tripepi G, Vajente N, et al. Vitamin K, vertebral fractures, vascular calcifications, and mortality: vItamin K Italian (VIKI) dialysis study. J Bone Miner Res 2012;27:2271–8.10.1002/jbmr.1677Search in Google Scholar PubMed

14. Hoogeveen EK, Halbesma N, Rothman KJ, Stijnen T, van Dijk S, Dekker FW, et al. Obesity and mortality risk among younger dialysis patients. Clin J Am Soc Nephrol 2012;7:280–8.10.2215/CJN.05700611Search in Google Scholar PubMed PubMed Central

15. Marles RJ, Roe AL, Oketch-Rabah HA. US Pharmacopeial convention safety evaluation of menaquinone-7, a form of vitamin K. Nutr Rev 2017;75:553–78.10.1093/nutrit/nux022Search in Google Scholar PubMed

16. Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MH, van der Meer IM, et al. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nut 2004;134:3100–5.10.1093/jn/134.11.3100Search in Google Scholar PubMed

17. Schrauben SJ, Hsu JY, Wright Nunes J, Fischer MJ, Srivastava A, Chen J, et al. Health behaviors in younger and older adults with CKD: results from the CRIC study. Kidney Int Rep 2018;4:80–93.10.1016/j.ekir.2018.09.003Search in Google Scholar PubMed PubMed Central

18. Pommer W. Preventive nephrology: the role of obesity in different stages of chronic kidney disease. Kidney Dis (Basel) 2018;4:199–204.10.1159/000490247Search in Google Scholar PubMed PubMed Central

19. Lespessailles E, Paccou J, Javier RM, Thomas T, Cortet B, GRIO Scientific Committee. Obesity, bariatric surgery and fractures. J Clin Endocrinol Metab 2019;104:4756–68.10.1210/jc.2018-02084Search in Google Scholar PubMed

20. Neogi T, Booth SL, Zhang YQ, Jacques PF, Terkeltaub R, Aliabadi P, et al. Low vitamin K status is associated with osteoarthritis in the hand and knee. Arthritis Rheum 2006;54:1255–61.10.1002/art.21735Search in Google Scholar PubMed

21. Neogi T, Felson DT, Sarno R, Booth SL. Vitamin K in hand osteoarthritis: results from a randomised clinical trial. Ann Rheum Dis 2008;67:1570–3.10.1136/ard.2008.094771Search in Google Scholar PubMed PubMed Central

22. Misra D, Booth SL, Tolstykh I, Felson DT, Nevitt MC, Lewis CE, et al. Vitamin K deficiency is associated with incident knee osteoarthritis. Am J Med 2013;126:243–8.10.1016/j.amjmed.2012.10.011Search in Google Scholar PubMed PubMed Central

23. Wallin R, Schurgers L, Wajih N. Effects of the blood coagulation vitamin K as an inhibitor of arterial calcification. Thromb Res 2008;122:411–7.10.1016/j.thromres.2007.12.005Search in Google Scholar PubMed PubMed Central

24. Parker BD, Ix JH, Cranenburg EC, Vermeer C, Whooley MA, Schurgers LJ. Association of kidney function and uncarboxylated matrix Gla protein: data from the Heart and Soul Study. Nephrol Dial Transplant 2009;24:2095–101.10.1093/ndt/gfp024Search in Google Scholar PubMed PubMed Central

25. Luo XH, Zhao LL, Yuan LQ, Wang M, Xie H, Liao EY. Development of arterial calcification in adiponectin-deficient mice: adiponectin regulates arterial calcification. J Bone Miner Res 2009;24:1461–8.10.1359/jbmr.090227Search in Google Scholar PubMed

26. Fusaro M, Gallieni M, Aghi A, Rizzo MA, Iervasi G, Nickolas TL, et al. Osteocalcin (bone GLA protein) levels, vascular calcifications, vertebral fractures and mortality in hemodialysis patients with diabetes mellitus. J Nephrol 2019;32:635–43.10.1007/s40620-019-00595-1Search in Google Scholar PubMed

27. Confavreux CB, Szulc P, Casey R, Boutroy S, Varennes A, Vilayphiou N, et al. Higher serum osteocalcin is associated with lower abdominal aortic calcification progression and longer 10-year survival in elderly men of the MINOS cohort. J Clin Endocrinol Metab 2013;98:1084–92.10.1210/jc.2012-3426Search in Google Scholar PubMed

Received: 2020-02-24
Accepted: 2020-04-12
Published Online: 2020-05-08
Published in Print: 2021-02-23

©2020 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Complex analytical procedures in diagnostic laboratories and the IVDR
  4. Review
  5. Re-examining ferritin-bound iron: current and developing clinical tools
  6. Opinion Papers
  7. Designing a diagnostic Total Testing Process as a base for supporting diagnostic stewardship
  8. The end of the laboratory developed test as we know it? Recommendations from a national multidisciplinary taskforce of laboratory specialists on the interpretation of the IVDR and its complications
  9. EFLM Papers
  10. The Academy of the European Federation of Clinical Chemistry and Laboratory Medicine and the European Register of Specialists in Laboratory Medicine: guide to the Academy and the Register, version 4 – 2020
  11. A proposed Common Training Framework for Specialists in Laboratory Medicine under EU Directive 2013/55/EC (The Recognition of Professional Qualifications)
  12. Guidelines and Recommendations
  13. High-sensitivity cardiac troponin I and T methods for the early detection of myocardial injury in patients on chemotherapy
  14. General Clinical Chemistry and Laboratory Medicine
  15. Measurement of serum 17-hydroxyprogesterone using isotope dilution liquid chromatography-tandem mass spectrometry candidate reference method and evaluation of the performance for three routine methods
  16. Evaluation of carbohydrate-deficient transferrin measurements on the V8 capillary electrophoresis system and comparison with the IFCC approved HPLC reference method and N-Latex immunonephelometric assay
  17. The clinical relevance of anti-dsDNA antibodies determined by the Elia™ dsDNA assay in patients with negative indirect immunofluorescence on the HEp-2 cell
  18. A hierarchical bivariate meta-analysis of diagnostic test accuracy to provide direct comparisons of immunoassays vs. indirect immunofluorescence for initial screening of connective tissue diseases
  19. Individual uromodulin serum concentration is independent of glomerular filtration rate in healthy kidney donors
  20. Comparison of iohexol plasma clearance formulas vs. inulin urinary clearance for measuring glomerular filtration rate
  21. Overweight-obesity is associated with decreased vitamin K2 levels in hemodialysis patients
  22. Cardiovascular Diseases
  23. Evaluating the performance of an updated high-sensitivity troponin T assay with increased tolerance to biotin
  24. Infectious Diseases
  25. The anti-inflammatory cytokine response characterized by elevated interleukin-10 is a stronger predictor of severe disease and poor outcomes than the pro-inflammatory cytokine response in coronavirus disease 2019 (COVID-19)
  26. Quantification of the HIV-1 total reservoir in the peripheral blood of naïve and treated patients by a standardised method derived from a commercial HIV-1 RNA quantification assay
  27. Comparison of the reliability of Gram-negative and Gram-positive flags of the Sysmex UF-5000 with manual Gram stain and urine culture results
  28. Evaluation of a turbidimetric C-reactive protein assay to monitor early-onset neonatal sepsis in South Kivu (Democratic Republic of the Congo)
  29. Corrigendum
  30. Corrigendum to: Procalcitonin (PCT)-guided antibiotic stewardship in Asia-Pacific countries: adaptation based on an expert consensus meeting
  31. Letters to the Editor
  32. Decision-making based on sFlt-1/PlGF ratios: are immunoassay results interchangeable for diagnosis or prognosis of preeclampsia?
  33. Inter-center agreement in the interpretation of oligoclonal bands
  34. A new founder BRCA1 haplotype identified in the Puglia region is associated with a specific age-related cancer onset in three unrelated families
  35. Predictive values of D-dimer for adverse pregnancy outcomes: a retrospective study
  36. A very uncommon haemoglobin value resulting from a severe acute malnutrition in a 16-month-old child in Ethiopia
  37. Ionized calcium measurements during continuous renal replacement therapy with regional citrate anticoagulation
  38. The hairy cell leukaemia oxymoron: monocytotic monocytopenia
  39. Perchlorate interference with electrolyte analysis
  40. False decrease in serum triglyceride and cholesterol due to massive ascorbate in a bowel preparation solution
https://doi.org/10.1515/cclm-2020-0194
Keywords for this article
BMI; hemodialysis; obesity; vitamin K

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Complex analytical procedures in diagnostic laboratories and the IVDR
  4. Review
  5. Re-examining ferritin-bound iron: current and developing clinical tools
  6. Opinion Papers
  7. Designing a diagnostic Total Testing Process as a base for supporting diagnostic stewardship
  8. The end of the laboratory developed test as we know it? Recommendations from a national multidisciplinary taskforce of laboratory specialists on the interpretation of the IVDR and its complications
  9. EFLM Papers
  10. The Academy of the European Federation of Clinical Chemistry and Laboratory Medicine and the European Register of Specialists in Laboratory Medicine: guide to the Academy and the Register, version 4 – 2020
  11. A proposed Common Training Framework for Specialists in Laboratory Medicine under EU Directive 2013/55/EC (The Recognition of Professional Qualifications)
  12. Guidelines and Recommendations
  13. High-sensitivity cardiac troponin I and T methods for the early detection of myocardial injury in patients on chemotherapy
  14. General Clinical Chemistry and Laboratory Medicine
  15. Measurement of serum 17-hydroxyprogesterone using isotope dilution liquid chromatography-tandem mass spectrometry candidate reference method and evaluation of the performance for three routine methods
  16. Evaluation of carbohydrate-deficient transferrin measurements on the V8 capillary electrophoresis system and comparison with the IFCC approved HPLC reference method and N-Latex immunonephelometric assay
  17. The clinical relevance of anti-dsDNA antibodies determined by the Elia™ dsDNA assay in patients with negative indirect immunofluorescence on the HEp-2 cell
  18. A hierarchical bivariate meta-analysis of diagnostic test accuracy to provide direct comparisons of immunoassays vs. indirect immunofluorescence for initial screening of connective tissue diseases
  19. Individual uromodulin serum concentration is independent of glomerular filtration rate in healthy kidney donors
  20. Comparison of iohexol plasma clearance formulas vs. inulin urinary clearance for measuring glomerular filtration rate
  21. Overweight-obesity is associated with decreased vitamin K2 levels in hemodialysis patients
  22. Cardiovascular Diseases
  23. Evaluating the performance of an updated high-sensitivity troponin T assay with increased tolerance to biotin
  24. Infectious Diseases
  25. The anti-inflammatory cytokine response characterized by elevated interleukin-10 is a stronger predictor of severe disease and poor outcomes than the pro-inflammatory cytokine response in coronavirus disease 2019 (COVID-19)
  26. Quantification of the HIV-1 total reservoir in the peripheral blood of naïve and treated patients by a standardised method derived from a commercial HIV-1 RNA quantification assay
  27. Comparison of the reliability of Gram-negative and Gram-positive flags of the Sysmex UF-5000 with manual Gram stain and urine culture results
  28. Evaluation of a turbidimetric C-reactive protein assay to monitor early-onset neonatal sepsis in South Kivu (Democratic Republic of the Congo)
  29. Corrigendum
  30. Corrigendum to: Procalcitonin (PCT)-guided antibiotic stewardship in Asia-Pacific countries: adaptation based on an expert consensus meeting
  31. Letters to the Editor
  32. Decision-making based on sFlt-1/PlGF ratios: are immunoassay results interchangeable for diagnosis or prognosis of preeclampsia?
  33. Inter-center agreement in the interpretation of oligoclonal bands
  34. A new founder BRCA1 haplotype identified in the Puglia region is associated with a specific age-related cancer onset in three unrelated families
  35. Predictive values of D-dimer for adverse pregnancy outcomes: a retrospective study
  36. A very uncommon haemoglobin value resulting from a severe acute malnutrition in a 16-month-old child in Ethiopia
  37. Ionized calcium measurements during continuous renal replacement therapy with regional citrate anticoagulation
  38. The hairy cell leukaemia oxymoron: monocytotic monocytopenia
  39. Perchlorate interference with electrolyte analysis
  40. False decrease in serum triglyceride and cholesterol due to massive ascorbate in a bowel preparation solution
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 12.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2020-0194/html
Scroll to top button