Skip to main content

Advertisement

SpringerLink
Log in

Associations of vitamin K status with mortality and cardiovascular events in peritoneal dialysis patients

  • Nephrology - Original paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Purpose

Vitamin K deficiency, expressed by a high level of desphospho-uncarboxylated matrix GLA protein (dp-ucMGP), is highly prevalent in dialysis patients. However, the predictive ability of the vitamin K status remains unclear in continuous ambulatory peritoneal dialysis (CAPD) patients.

Methods

158 prevalent CAPD patients with a median level of dp-ucMGP of 1093 (752, 1485) pmol/L were enrolled. Patient outcomes including all-cause mortality and cardiovascular events (CVEs) were recorded during follow-up. Survival curves were performed using Kaplan–Meier method, and the influences of dp-ucMGP on outcomes were analyzed by Cox regression models.

Results

A total of 59 deaths and 82 new episodes of CVEs occurred during median follow-up of 31.4 ± 13.1 months (range: 3.8–48.0 months). Kaplan–Meier analysis revealed patients with higher dp-ucMGP levels (≥ 1093 pmol/L) had an increased risk for both mortality (P = 0.005) and CVEs (P < 0.001). Multivariable Cox regression confirmed that higher dp-ucMGP levels increase the mortality risk [hazard ratio (HR), 1.763; 95% CI 1.045–3.291] and CVEs (HR, 1.846; 95% CI 1.074–3.172). For every 100 pmol/L increase in serum dp-ucMGP, the adjusted HRs for mortality and CVEs were 1.054 (95% CI 1.008–1.106) and 1.034 (95% CI 1.012–1.089), respectively.

Conclusions

Vitamin K deficiency, as expressed by high dp-ucMGP levels, showed independently associations with mortality and CVEs in CAPD patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Ortiz A, Covic A, Fliser D, Fouque D, Goldsmith D, Kanbay M, Mallamaci F, Massy ZA, Rossignol P, Vanholder R, Wiecek A, Zoccali C, London GM (2014) Epidemiology, contributors to, and clinical trials of mortality risk in chronic kidney failure. Lancet 383:1831–1843

    Article  PubMed  Google Scholar 

  2. Sarnak MJ, Foley RN (2011) Cardiovascular mortality in the general population versus dialysis: a glass half full or empty? Am J Kidney Dis 58:4–6

    Article  PubMed  Google Scholar 

  3. Mavrakanas TA, Charytan DM (2016) Cardiovascular complications in chronic dialysis patients. Curr Opin Nephrol Hypertens 25:536–544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. London GM, Guerin AP, Marchais SJ, Metivier F, Pannier B, Adda H (2003) Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 18:1731–1740

    Article  PubMed  Google Scholar 

  5. Fusaro M, Mereu MC, Aghi A, Iervasi G, Gallieni M (2017) Vitamin K and bone. Clin Cases Miner Bone Metab 14:200–206

    Article  PubMed  PubMed Central  Google Scholar 

  6. Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G (1997) Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 386:78–81

    Article  CAS  Google Scholar 

  7. Munroe PB, Olgunturk RO, Fryns JP, Van Maldergem L, Ziereisen F, Yuksel B, Gardiner RM, Chung E (1999) Mutations in the gene encoding the human matrix Gla protein cause keutel syndrome. Nat Genet 21:142–144

    Article  CAS  PubMed  Google Scholar 

  8. Murshed M, Schinke T, McKee MD, Karsenty G (2004) Extracellular matrix mineralization is regulated locally; different roles of two Gla-containing proteins. J Cell Biol 165:625–630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Schurgers LJ, Spronk HM, Skepper JN, Hackeng TM, Shanahan CM, Vermeer C, Weissberg PL, Proudfoot D (2007) Post-translational modifications regulate matrix Gla protein function: importance for inhibition of vascular smooth muscle cell calcification. J Thromb Haemost 5:2503–2511

    Article  CAS  PubMed  Google Scholar 

  10. Rennenberg RJ, de Leeuw PW, Kessels AG, Schurgers LJ, Vermeer C, van Engelshoven JM, Kemerink GJ, Kroon AA (2010) Calcium scores and matrix Gla protein levels: association with vitamin K status. Eur J Clin Invest 40:344–349

    Article  CAS  PubMed  Google Scholar 

  11. Shea MK, O’Donnell CJ, Vermeer C, Magdeleyns EJ, Crosier MD, Gundberg CM, Ordovas JM, Kritchevsky SB, Booth SL (2011) Circulating uncarboxylated matrix Gla protein is associated with vitamin K nutritional status, but not coronary artery calcium, in older adults. J Nutr 141:1529–1534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Dalmeijer GW, van der Schouw YT, Vermeer C, Magdeleyns EJ, Schurgers LJ, Beulens JW (2013) Circulating matrix Gla protein is associated with coronary artery calcification and vitamin K status in healthy women. J Nutr Biochem 24:624–628

    Article  CAS  PubMed  Google Scholar 

  13. Cranenburg EC, Koos R, Schurgers LJ, Magdeleyns EJ, Schoonbrood TH, Landewe RB, Brandenburg VM, Bekers O, Vermeer C (2010) Characterisation and potential diagnostic value of circulating matrix Gla protein (MGP) species. Thromb Haemost 104:811–822

    Article  CAS  PubMed  Google Scholar 

  14. Westenfeld R, Krueger T, Schlieper G, Cranenburg EC, Magdeleyns EJ, Heidenreich S, Holzmann S, Vermeer C, Jahnen-Dechent W, Ketteler M, Floege J, Schurgers LJ (2012) Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. Am J Kidney Dis 59:186–195

    Article  CAS  PubMed  Google Scholar 

  15. Theuwissen E, Cranenburg EC, Knapen MH, Magdeleyns EJ, Teunissen KJ, Schurgers LJ, Smit E, Vermeer C (2012) Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects. Br J Nutr 108:1652–1657

    Article  CAS  PubMed  Google Scholar 

  16. Nimptsch K, Rohrmann S, Kaaks R, Linseisen J (2010) Dietary vitamin K intake in relation to cancer incidence and mortality: results from the heidelberg cohort of the european prospective investigation into cancer and nutrition (EPIC-Heidelberg). Am J Clin Nutr 91:1348–1358

    Article  CAS  PubMed  Google Scholar 

  17. Dalmeijer GW, van der Schouw YT, Magdeleyns EJ, Vermeer C, Verschuren WM, Boer JM, Beulens JW (2013) Matrix Gla protein species and risk of cardiovascular events in type 2 diabetic patients. Diabetes Care 36:3766–3771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ueland T, Gullestad L, Dahl CP, Aukrust P, Aakhus S, Solberg OG, Vermeer C, Schurgers LJ (2010) Undercarboxylated matrix Gla protein is associated with indices of heart failure and mortality in symptomatic aortic stenosis. J Intern Med 268:483–492

    Article  CAS  PubMed  Google Scholar 

  19. Mayer OJ, Seidlerova J, Bruthans J, Filipovsky J, Timoracka K, Vanek J, Cerna L, Wohlfahrt P, Cifkova R, Theuwissen E, Vermeer C (2014) Desphospho-uncarboxylated matrix Gla-protein is associated with mortality risk in patients with chronic stable vascular disease. Atherosclerosis 235:162–168

    Article  CAS  PubMed  Google Scholar 

  20. Schlieper G, Westenfeld R, Kruger T, Cranenburg EC, Magdeleyns EJ, Brandenburg VM, Djuric Z, Damjanovic T, Ketteler M, Vermeer C, Dimkovic N, Floege J, Schurgers LJ (2011) Circulating nonphosphorylated carboxylated matrix Gla protein predicts survival in ESRD. J Am Soc Nephrol 22:387–395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Elliott MJ, Booth SL, Hopman WM, Holden RM (2014) Assessment of potential biomarkers of subclinical vitamin K deficiency in patients with end-stage kidney disease. Can J Kidney Health Dis 1:13

    Article  PubMed  PubMed Central  Google Scholar 

  22. Weiner DE, Tighiouart H, Vlagopoulos PT, Griffith JL, Salem DN, Levey AS, Sarnak MJ (2005) Effects of anemia and left ventricular hypertrophy on cardiovascular disease in patients with chronic kidney disease. J Am Soc Nephrol 16:1803–1810

    Article  PubMed  Google Scholar 

  23. Xu Q, Xiong L, Fan L, Xu F, Yang Y, Li H, Peng X, Cao S, Zheng Z, Yang X, Yu X, Mao H (2015) Association of pulmonary hypertension with mortality in incident peritoneal dialysis patients. Perit Dial Int 35:537–544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Rocco MV, Jordan JR, Burkart JM (1994) Determination of peritoneal transport characteristics with 24-hour dialysate collections: dialysis adequacy and transport test. J Am Soc Nephrol 5:1333–1338

    CAS  PubMed  Google Scholar 

  25. van Olden RW, Krediet RT, Struijk DG, Arisz L (1996) Measurement of residual renal function in patients treated with continuous ambulatory peritoneal dialysis. J Am Soc Nephrol 7:745–750

    PubMed  Google Scholar 

  26. Sahn DJ, DeMaria A, Kisslo J, Weyman A (1978) Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 58:1072–1083

    Article  CAS  PubMed  Google Scholar 

  27. Tarrass F, Benjelloun M, Zamd M, Medkouri G, Hachim K, Benghanem MG, Ramdani B (2006) Heart valve calcifications in patients with end-stage renal disease: analysis for risk factors. Nephrology (Carlton) 11:494–496

    Article  Google Scholar 

  28. Choi MJ, Kim JK, Kim SG, Kim SE, Kim SJ, Kim HJ, Song YR (2013) Association between cardiac valvular calcification and myocardial ischemia in asymptomatic high-risk patients with end-stage renal disease. Atherosclerosis 229:369–373

    Article  CAS  PubMed  Google Scholar 

  29. Wang AY, Woo J, Lam CW, Wang M, Chan IH, Gao P, Lui SF, Li PK, Sanderson JE (2005) Associations of serum fetuin-A with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients. Nephrol Dial Transplant 20:1676–1685

    Article  CAS  PubMed  Google Scholar 

  30. Kurnatowska I, Grzelak P, Masajtis-Zagajewska A, Kaczmarska M, Stefanczyk L, Vermeer C, Maresz K, Nowicki M (2016) Plasma desphospho-uncarboxylated matrix Gla protein as a marker of kidney damage and cardiovascular risk in advanced stage of chronic kidney disease. Kidney Blood Press Res 41:231–239

    Article  CAS  PubMed  Google Scholar 

  31. Fusaro M, Plebani M, Iervasi G, Gallieni M (2017) Vitamin K deficiency in chronic kidney disease: evidence is building up. Am J Nephrol 45:1–3

    Article  PubMed  Google Scholar 

  32. Dalmeijer GW, van der Schouw YT, Magdeleyns E, Ahmed N, Vermeer C, Beulens JW (2012) The effect of menaquinone-7 supplementation on circulating species of matrix Gla protein. Atherosclerosis 225:397–402

    Article  CAS  PubMed  Google Scholar 

  33. Dam V, Dalmeijer GW, Vermeer C, Drummen NE, Knapen MH, van der Schouw YT, Beulens JW (2015) Association between vitamin K and the metabolic syndrome: a 10-year follow-up study in adults. J Clin Endocrinol Metab 100:2472–2479

    Article  CAS  PubMed  Google Scholar 

  34. Caluwe R, Vandecasteele S, Van Vlem B, Vermeer C, De Vriese AS (2014) Vitamin K2 supplementation in haemodialysis patients: a randomized dose-finding study. Nephrol Dial Transplant 29:1385–1390

    Article  CAS  PubMed  Google Scholar 

  35. Fusaro M, D’Alessandro C, Noale M, Tripepi G, Plebani M, Veronese N, Iervasi G, Giannini S, Rossini M, Tarroni G, Lucatello S, Vianello A, Santinello I, Bonfante L, Fabris F, Sella S, Piccoli A, Naso A, Ciurlino D, Aghi A, Gallieni M, Cupisti A (2017) Low vitamin K1 intake in haemodialysis patients. Clin Nutr 36:601–607

    Article  CAS  PubMed  Google Scholar 

  36. Delanaye P, Krzesinski JM, Warling X, Moonen M, Smelten N, Medart L, Pottel H, Cavalier E (2014) Dephosphorylated-uncarboxylated matrix Gla protein concentration is predictive of vitamin K status and is correlated with vascular calcification in a cohort of hemodialysis patients. BMC Nephrol 15:145

    Article  PubMed  PubMed Central  Google Scholar 

  37. Shea MK, Booth SL, Massaro JM, Jacques PF, D’Agostino RS, Dawson-Hughes B, Ordovas JM, O’Donnell CJ, Kathiresan S, Keaney JJ, Vasan RS, Benjamin EJ (2008) Vitamin K and vitamin D status: associations with inflammatory markers in the framingham offspring study. Am J Epidemiol 167:313–320

    Article  PubMed  Google Scholar 

  38. Boxma PY, van den Berg E, Geleijnse JM, Laverman GD, Schurgers LJ, Vermeer C, Kema IP, Muskiet FA, Navis G, Bakker SJ, de Borst MH (2012) Vitamin K intake and plasma desphospho-uncarboxylated matrix Gla-protein levels in kidney transplant recipients. PLoS ONE 7:e47991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Reddi K, Henderson B, Meghji S, Wilson M, Poole S, Hopper C, Harris M, Hodges SJ (1995) Interleukin 6 production by lipopolysaccharide-stimulated human fibroblasts is potently inhibited by naphthoquinone (Vitamin K) compounds. Cytokine 7:287–290

    Article  CAS  PubMed  Google Scholar 

  40. Ohsaki Y, Shirakawa H, Hiwatashi K, Furukawa Y, Mizutani T, Komai M (2006) Vitamin K suppresses lipopolysaccharide-induced inflammation in the rat. Biosci Biotechnol Biochem 70:926–932

    Article  CAS  PubMed  Google Scholar 

  41. Schurgers LJ Vitamin K (2013) Key vitamin in controlling vascular calcification in chronic kidney disease. Kidney Int 83:782–784

    Article  CAS  PubMed  Google Scholar 

  42. Schurgers LJ, Barreto DV, Barreto FC, Liabeuf S, Renard C, Magdeleyns EJ, Vermeer C, Choukroun G, Massy ZA (2010) The circulating inactive form of matrix Gla protein is a surrogate marker for vascular calcification in chronic kidney disease: a preliminary report. Clin J Am Soc Nephrol 5:568–575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Vliegenthart R, Hollander M, Breteler MM, van der Kuip DA, Hofman A, Oudkerk M, Witteman JC (2002) Stroke is associated with coronary calcification as detected by electron-beam CT: the rotterdam coronary calcification study. Stroke 33:462–465

    Article  PubMed  Google Scholar 

  44. Benjamin EJ, Plehn JF, D’Agostino RB, Belanger AJ, Comai K, Fuller DL, Wolf PA, Levy D (1992) Mitral annular calcification and the risk of stroke in an elderly cohort. N Engl J Med 327:374–379

    Article  CAS  PubMed  Google Scholar 

  45. De Marco M, Gerdts E, Casalnuovo G, Migliore T, Wachtell K, Boman K, Dahlof B, Olsen MH, Kizer JR, Devereux RB, de Simone G (2013) Mitral annular calcification and incident ischemic stroke in treated hypertensive patients: the life study. Am J Hypertens 26:567–573

    Article  PubMed  Google Scholar 

  46. Dalmeijer GW, van der Schouw YT, Magdeleyns EJ, Vermeer C, Verschuren WM, Boer JM, Beulens JW (2014) Circulating desphospho-uncarboxylated matrix gamma-carboxyglutamate protein and the risk of coronary heart disease and stroke. J Thromb Haemost 12:1028–1034

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We express our deepest gratitude to all patients who participated in the study and all nephrologists and nurses in our PD center for their helpful assistance.

Funding

This research was funded by Medical Scientific Research Foundation of Guangdong Province, China (Grant No. 2015122194432203-A201563).

Author information

Author notes

  1. Qing dong Xu and Huankai Guo have contributed equally to this work.

Authors and Affiliations

  1. Department of Nephrology, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Guangdong, People’s Republic of China

    Qingdong Xu, Huankai Guo, Jiexin Chen, Ming Su, Siying Chen, Songqin Jiang & Xiaofeng Shi

  2. Department of Nephrology, Central Municipal Hospital of Huizhou, Guangdong, People’s Republic of China

    Shirong Cao

  3. Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangdong, People’s Republic of China

    Qian Zhou

  4. Department of Nephrology, the 2nd Affiliated Hospital of Guangzhou Medical University, Guangdong, People’s Republic of China

    Yueqiang Wen

Authors
  1. Qingdong Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Huankai Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shirong Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qian Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jiexin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ming Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Siying Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Songqin Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xiaofeng Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yueqiang Wen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qingdong Xu.

Ethics declarations

Conflict of interest

The authors have no financial conflicts of interest to declare.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, Q., Guo, H., Cao, S. et al. Associations of vitamin K status with mortality and cardiovascular events in peritoneal dialysis patients. Int Urol Nephrol 51, 527–534 (2019). https://doi.org/10.1007/s11255-019-02080-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-019-02080-x

Keywords

Search

Navigation