Warfarin is associated with the risk of vascular calcification in abdominal aorta in hemodialysis patients: a multicenter case-control study

keven, kenan; Üstüner, Evren; Eren Sadioğlu, Rezzan; nergizoglu, gökhan; ergün, ihsan; Ecder, Tevfik

doi:10.3906/sag-2104-221

Warfarin is associated with the risk of vascular calcification in abdominal aorta in hemodialysis patients: a multicenter case-control study

Rezzan EREN SADİOĞLU, (Ankara Üniversitesi, Tıp Fakültesi, İç Hastalıkları Anabilim Dalı, Nefroloji Anabilim Dalı, Ankara, Türkiye)

Evren ÜSTÜNER, (Ankara Üniversitesi, Tıp Fakültesi, Radyoloji Anabilim Dalı, Ankara, Türkiye)

İhsan ERGÜN, (Ufuk Üniversitesi, Tıp Fakültesi, İç Hastalıkları Anabilim Dalı, Nefroloji Anabilim Dalı, Ankara, Türkiye)

Süleyman Tevfik ECDER, (Demiroğlu Bilim Üniversitesi, Tıp Fakültesi, Nefroloji Anabilim Dalı, İç Hastalıkları Anabilim Dalı, İstanbul, Türkiye)

Gökhan NERGİZOĞLU, (Ankara Üniversitesi, Tıp Fakültesi, İç Hastalıkları Anabilim Dalı, Nefroloji Anabilim Dalı, Ankara, Türkiye)

Kenan KEVEN (Ankara Üniversitesi, Tıp Fakültesi, İç Hastalıkları Anabilim Dalı, Nefroloji Anabilim Dalı, Ankara, Türkiye)

Turkish Journal of Medical Sciences

5 0

Yıl: 2021 Cilt: 51 Sayı: 5 Sayfa Aralığı: 2607 - 2615 Metin Dili: İngilizce DOI: 10.3906/sag-2104-221 İndeks Tarihi: 07-01-2022

Warfarin is associated with the risk of vascular calcification in abdominal aorta in hemodialysis patients: a multicenter case-control study

Öz:

Background/aim: Vascular calcifications (VCs), recognized risk factor for increased mortality, are highly prevalent in hemodialysis (HD) patients. We aimed to investigate the relation between VC and warfarin use with plain radiography. Materials and methods: VCs were assessed using Adragao (radial and digital) and Kauppila (aortic) scores in 76 HD patients from six centers. Out of a total 711 HD patients, there were 32 (4.5%) who had been treated with warfarin for at least 1 year, and we included 44 control patients. Results: Of the patients, 47% were females, the mean age was 66 ± 9 years, 23% were diabetics, the mean dialysis vintage was 68 ± 38 months. In warfarin group, median Kauppila score was higher than in control group [11 vs 6.5, (25%–75% percentile, 5 vs. 15), p = 0.032] and the percentage of the patients with a Kauppila score of >6 was higher, as well (76.6% vs. 50%; p = 0.029). Median Adragao score was not significantly different between the two groups [7 vs. 6, (%25,%75 percentile 6 vs. 8), p = 0.17]. Logistic regression analysis revealed that warfarin treatment was independently associated with Kauppila scores of >6 (OR 3.60, 95% CI 1.18–10.9, p = 0.024). Conclusion: In this study, we found that warfarin is associated to vascular calcifications, especially in aorta of HD patients.Key words: Hemodialysis, vascular calcification, vitamin K, warfarin

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Blacher J, Guerin AP, Pannier B, Marchais SJ, London GM. Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension 2001; 38 (4): 938-942. doi: 10.1161/hy1001.096358
2. Chatrou ML, Winckers K, Hackeng TM, Reutelingsperger CP, Schurgers LJ. Vascular calcification: the price to pay for anticoagulation therapy with vitamin K-antagonists. Blood Reviews 2012; 26 (4): 155-166. doi: 10.1016/j.blre.2012.03.002
3. Schurgers LJ, Joosen IA, Laufer EM, Chatrou ML, Herfs M et al. Vitamin K-antagonists accelerate atherosclerotic calcification and induce a vulnerable plaque phenotype. PLOS ONE 2012; 7 (8): e43229. doi: 10.1371/journal.pone0043229
4. Tsai MT, Chen YY, Chang WJ, Li SY. Warfarin accelerated vascular calcification and worsened cardiac dysfunction in remnant kidney mice. Journal of Chinese Medical Association 2018; 81 (4): 324-330. doi: 10.1016/j.jcma.2017.08.021
5. Weijs B, Blaauw Y, Rennenberg RJ, Schurgers LJ, Timmermans CC et al. Patients using vitamin K antagonists show increased levels of coronary calcification: an observational study in lowrisk atrial fibrillation patients. European Heart Journal 2011; 32 (20): 2555-2562. doi: 10.1093/eurheartj/ehr226
6. Rennenberg RJ, van Varik BJ, Schurgers LJ, Hamulyak K, Ten Cate H et al. Chronic coumarin treatment is associated with increased extracoronary arterial calcification in humans. Blood 2010; 115 (24): 5121-5123. doi: 10.1182/blood-2010-01-264598
7. Reynolds JL, Joannides AJ, Skepper JN, McNair R, Schurgers LJ et al. Human vascular smooth muscle cells undergo vesiclemediated calcification in response to changes in extracellular calcium and phosphate concentrations: a potential mechanism for accelerated vascular calcification in ESRD. Journal of the American Society of Nephrology 2004; 15 (11): 2857-2867. doi: 10.1097/01.ASN.0000141960.01035.28
8. Yamada S, Giachelli CM. Vascular calcification in CKD-MBD: Roles for phosphate, FGF23, and Klotho. Bone 2017; 100: 87-93. doi: 10.1016/j.bone.2016.11.012
9. Tsai C, Marcus LQ, Patel P, Battistella M. Warfarin Use in Hemodialysis Patients With Atrial Fibrillation: A Systematic Review of Stroke and Bleeding Outcomes. Canadian Journal of Kidney Health and Disease 2017; 4: 2054358117735532. doi:10.1177/2054358117735532
10. Cozzolino M, Missaglia E, Ortiz A, Bellasi A, Adragao T et al. Vascular calcification in chronic kidney disease. Recenti Progressi in Medicina 2010; 101 (11): 442-452. doi: 10.1701/526.6287
11. Cranenburg EC, Schurgers LJ, Uiterwijk HH, Beulens JW, Dalmeijer GW et al. Vitamin K intake and status are low in hemodialysis patients. Kidney International 2012; 82 (5): 605- 610. doi: 10.1038/ki.2012.191
12. De Vriese AS, Caluwe R, Pyfferoen L, De Bacquer D, De Boeck K et al. Multicenter Randomized Controlled Trial of Vitamin K Antagonist Replacement by Rivaroxaban with or without Vitamin K2 in Hemodialysis Patients with Atrial Fibrillation: the Valkyrie Study. Journal of the American Society of Nephrology 2020; 31 (1): 186-196. doi: 10.1681/ASN.2019060579
13. Fusaro M, Tripepi G, Noale M, Plebani M, Zaninotto M et al. Prevalence of vertebral fractures, vascular calcifications, and mortality in warfarin treated hemodialysis patients. Current Vascular Pharmacology 2015; 13 (2): 248-258. doi: 10.2174/15701611113119990146
14. Gorriz JL, Molina P, Cerveron MJ, Vila R, Bover J et al. Vascular calcification in patients with nondialysis CKD over 3 years. Clinical Journal of the American Society of Nephrology 2015; 10 (4): 654-666. doi: 10.2215/CJN.07450714
15. Adragao T, Pires A, Birne R, Curto JD, Lucas C et al. A plain X-ray vascular calcification score is associated with arterial stiffness and mortality in dialysis patients. Nephrology Dialysis Transplantation 2009; 24 (3): 997-1002. doi: 10.1093/ndt/ gfn584
16. Kauppila LI, Polak JF, Cupples LA, Hannan MT, Kiel DP et al. New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: a 25-year follow-up study. Atherosclerosis 1997; 132 (2): 245-250. doi: 10.1016/ s0021-9150(97)00106-8
17. Adragao T, Pires A, Lucas C, Birne R, Magalhaes L et al. A simple vascular calcification score predicts cardiovascular risk in haemodialysis patients. Nephrology Dialysis Transplantation 2004; 19 (6): 1480-1488.doi: 10.1093/ndt/gfh217
18. Delanaye P, Krzesinski JM, Warling X, Moonen M, Smelten N et al. 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 Nephrology 2014; 15: 145. doi: 10.1186/1471-2369-15- 145
19. Westenfeld R, Krueger T, Schlieper G, Cranenburg EC, Magdeleyns EJ et al. Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. American Journal of Kidney Diseases 2012; 59 (2): 186-195. doi: 10.1053/j.ajkd.2011.10.041
20. Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. The New England Journal of Medicine 2000; 342 (20): 1478-1483. doi: 10.1056/ NEJM200005183422003
21. Lilien MR, Groothoff JW. Cardiovascular disease in children with CKD or ESRD. Nature Reviews Nephrolgy 2009; 5 (4): 229-235. doi: 10.1038/nrneph.2009.10
22. Becker CR, Jakobs TF, Aydemir S, Becker A, Knez A et al. Helical and single-slice conventional CT versus electron beam CT for the quantification of coronary artery calcification. American Journal of Roentgenology 2000; 174 (2): 543-547. doi:10.2214/ajr.174.2.1740543
23. Bellasi A, Ferramosca E, Muntner P, Ratti C, Wildman RP et al. Correlation of simple imaging tests and coronary artery calcium measured by computed tomography in hemodialysis patients. Kidney International 2006; 70 (9): 1623-1628. doi: 10.1038/sj.ki.5001820
24. Kidney Disease: Improving Global Outcomes CKD-MBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney International Supplement (2011) 2017; 7 (1): 1-59. doi: 10.1016/j.kisu.2017.04.001
25. Witteman JC, Grobbee DE, Valkenburg HA, van Hemert AM, Stijnen T et al. J-shaped relation between change in diastolic blood pressure and progression of aortic atherosclerosis. Lancet 1994; 343 (8896): 504-7. doi: 10.1016/s0140-6736(94)91459-1
26. Mourad JJ, Girerd X, Boutouyrie P, Laurent S, Safar M et al. Increased stiffness of radial artery wall material in end-stage renal disease. Hypertension 1997; 30 (6): 1425-1430. doi: 10.1161/01.hyp.30.6.1425
27. Kwon HY, Lee OH, Kim MJ, Joo WC, Lee SY et al. The association between mortality and abdominal aortic calcification and relation between its progression and serum calcium concentration in chronic hemodialysis patients. Kidney Research and Clinical Practice 2014; 33 (2): 95-102. doi: 10.1016/j.krcp.2014.04.003
28. Shroff R, Long DA, Shanahan C. Mechanistic insights into vascular calcification in CKD. Journal of the American Society of Nephrology 2013; 24 (2): 179-189. doi: 10.1681/ ASN.2011121191
29. Choi SR, Lee YK, Cho AJ, Park HC, Han CH et al. Malnutrition, inflammation, progression of vascular calcification and survival: Inter-relationships in hemodialysis patients. PloS one 2019; 14 (5): e0216415. doi: 10.1371/journal.pone.0216415
30. Floege J, Kubo Y, Floege A, Chertow GM, Parfrey PS. The Effect of Cinacalcet on Calcific Uremic Arteriolopathy Events in Patients Receiving Hemodialysis: The EVOLVE Trial. Clinical Journal of the American Society of Nephrology 2015; 10 (5): 800-807. doi: 10.2215/CJN.10221014
31. Kruger T, Floege J. Coumarin use in dialysis patients with atrial fibrillation--more harm than benefit? Nephrology Dialysis Transplantation 2009; 24 (11): 3284-3285. doi: 10.2215/ CJN.10221014
32. Siontis KC, Zhang X, Eckard A, Bhave N, Schaubel DE et al. Outcomes Associated With Apixaban Use in Patients With End-Stage Kidney Disease and Atrial Fibrillation in the United States. Circulation 2018; 138 (15): 1519-1529. doi:10.1161/ CIRCULATIONAHA.118.035418

APA	Eren Sadioğlu R, Üstüner E, ergün i, Ecder T, nergizoglu g, keven k (2021). Warfarin is associated with the risk of vascular calcification in abdominal aorta in hemodialysis patients: a multicenter case-control study. , 2607 - 2615. 10.3906/sag-2104-221
Chicago	Eren Sadioğlu Rezzan,Üstüner Evren,ergün ihsan,Ecder Tevfik,nergizoglu gökhan,keven kenan Warfarin is associated with the risk of vascular calcification in abdominal aorta in hemodialysis patients: a multicenter case-control study. (2021): 2607 - 2615. 10.3906/sag-2104-221
MLA	Eren Sadioğlu Rezzan,Üstüner Evren,ergün ihsan,Ecder Tevfik,nergizoglu gökhan,keven kenan Warfarin is associated with the risk of vascular calcification in abdominal aorta in hemodialysis patients: a multicenter case-control study. , 2021, ss.2607 - 2615. 10.3906/sag-2104-221
AMA	Eren Sadioğlu R,Üstüner E,ergün i,Ecder T,nergizoglu g,keven k Warfarin is associated with the risk of vascular calcification in abdominal aorta in hemodialysis patients: a multicenter case-control study. . 2021; 2607 - 2615. 10.3906/sag-2104-221
Vancouver	Eren Sadioğlu R,Üstüner E,ergün i,Ecder T,nergizoglu g,keven k Warfarin is associated with the risk of vascular calcification in abdominal aorta in hemodialysis patients: a multicenter case-control study. . 2021; 2607 - 2615. 10.3906/sag-2104-221
IEEE	Eren Sadioğlu R,Üstüner E,ergün i,Ecder T,nergizoglu g,keven k "Warfarin is associated with the risk of vascular calcification in abdominal aorta in hemodialysis patients: a multicenter case-control study." , ss.2607 - 2615, 2021. 10.3906/sag-2104-221
ISNAD	Eren Sadioğlu, Rezzan vd. "Warfarin is associated with the risk of vascular calcification in abdominal aorta in hemodialysis patients: a multicenter case-control study". (2021), 2607-2615. https://doi.org/10.3906/sag-2104-221

APA	Eren Sadioğlu R, Üstüner E, ergün i, Ecder T, nergizoglu g, keven k (2021). Warfarin is associated with the risk of vascular calcification in abdominal aorta in hemodialysis patients: a multicenter case-control study. Turkish Journal of Medical Sciences, 51(5), 2607 - 2615. 10.3906/sag-2104-221
Chicago	Eren Sadioğlu Rezzan,Üstüner Evren,ergün ihsan,Ecder Tevfik,nergizoglu gökhan,keven kenan Warfarin is associated with the risk of vascular calcification in abdominal aorta in hemodialysis patients: a multicenter case-control study. Turkish Journal of Medical Sciences 51, no.5 (2021): 2607 - 2615. 10.3906/sag-2104-221
MLA	Eren Sadioğlu Rezzan,Üstüner Evren,ergün ihsan,Ecder Tevfik,nergizoglu gökhan,keven kenan Warfarin is associated with the risk of vascular calcification in abdominal aorta in hemodialysis patients: a multicenter case-control study. Turkish Journal of Medical Sciences, vol.51, no.5, 2021, ss.2607 - 2615. 10.3906/sag-2104-221
AMA	Eren Sadioğlu R,Üstüner E,ergün i,Ecder T,nergizoglu g,keven k Warfarin is associated with the risk of vascular calcification in abdominal aorta in hemodialysis patients: a multicenter case-control study. Turkish Journal of Medical Sciences. 2021; 51(5): 2607 - 2615. 10.3906/sag-2104-221
Vancouver	Eren Sadioğlu R,Üstüner E,ergün i,Ecder T,nergizoglu g,keven k Warfarin is associated with the risk of vascular calcification in abdominal aorta in hemodialysis patients: a multicenter case-control study. Turkish Journal of Medical Sciences. 2021; 51(5): 2607 - 2615. 10.3906/sag-2104-221
IEEE	Eren Sadioğlu R,Üstüner E,ergün i,Ecder T,nergizoglu g,keven k "Warfarin is associated with the risk of vascular calcification in abdominal aorta in hemodialysis patients: a multicenter case-control study." Turkish Journal of Medical Sciences, 51, ss.2607 - 2615, 2021. 10.3906/sag-2104-221
ISNAD	Eren Sadioğlu, Rezzan vd. "Warfarin is associated with the risk of vascular calcification in abdominal aorta in hemodialysis patients: a multicenter case-control study". Turkish Journal of Medical Sciences 51/5 (2021), 2607-2615. https://doi.org/10.3906/sag-2104-221