nidНефрология и диализNephrology and Dialysis1680-44222618-9801Российское диализное обществоnid-1612Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESНаследуемые и приобретенные тромбофилии как факторы риска тромбоза артериовенозной фистулы у больных на программном гемодиализеHeritable and acquired thrombophilias and the risk for hemodialysis arteriovenous fistula thrombosisШилоВ. Ю.ShiloV. Yu.noemail@neicon.ruДенисовА. Ю.DenisovA. Yu.noemail@neicon.ruКозловаТ. В.KozlovaT. V.tkozlova@rol.ruЦентр Диализа при ГКБ № 20Russian FederationМосковская медицинская академия им. И.М. Сеченова, г. МоскваRussian Federation20052506202572161167Copyright © Шило В.Ю., Денисов А.Ю., Козлова Т.В., 20252025Шило В.Ю., Денисов А.Ю., Козлова Т.В.Shilo V.Y., Denisov A.Y., Kozlova T.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephro.ru/jour/article/view/1612

Введение. Потеря сосудистого доступа либо его дисфункция вследствие тромбоза остаются одной из ведущих клинических проблем у больных, получающих лечение программным гемодиализом. Среди возможных факторов риска тромбоза сосудистого доступа обсуждается гипергомоцистеинемия и мутации генов факторов свертывания. Целью исследования явилось сравнительное изучение уровня гомоцистеина и генетических факторов риска тромбозов (мутации Лейдена, мутации G20210A, мутации в гене MTHFR) у лиц, перенесших один и более эпизод тромбоза сосудистого доступа, и в контрольной группе диализных пациентов без тромбоза. Материал и методы. В ретроспективный анализ были включены 127 больных с терминальной хронической почечной недостаточностью, получавшие лечение гемодиализом. Анализировалась функция только нативной артериовенозной фистулы. Включенные в исследование пациенты были распределены на две группы с учетом наличия (основная группа - 42 пациента) или отсутствия (контрольная группа - 85 пациентов) тромбоза сосудистого доступа. Результаты. Показано, что уровень гомоцистеина у всех пациентов достоверно отличался от таковых показателей у здоровых лиц (27,5 ± 9,34 против 11,2 ± 3,54 мкмоль/л, p < 0,05), но не различался между контрольной и экспериментальной группой (28,3 ± 5,1 против 25,8 ± 6,3 мкмоль/л). Среди пациентов с наличием и отсутствием тромбоза сосудистого доступа частота гетерозиготных мутаций фактора V (Leiden) составляла соответственно 4,7 и 3,5%, гетерозиготной мутации MTHFR - 28,6 и 31,7%, гомозиготной мутации MTHFR - 2,4 и 3,5%, сочетанных мутаций (MTHFR + Leiden) - 2,4 и 3,5%. Достоверных различий в распространенности ни по одному из типов мутаций в сопоставлявшихся группах выявлено не было. Заключение. Системные факторы риска венозного тромбоза, такие, как уровень гомоцистеина и мутации генов факторов гемокоагуляции, не влияют на частоту тромбоза артериовенозной фистулы. Необходимо проведение проспективных, многоцентровых исследований для дальнейшего изучения данной проблемы.

Background. Vascular access thrombosis is the most common complication in hemodialysis patients. The role of thrombophilia in access thrombosis is not established. Among the risk factors that have been proposed high blood concentrations of total homocysteine and hereditary gene mutations have been considered, but the findings available are controversial. The aim of the study was to compare serum level of homocysteine and genetic thrombosis risk factors (Leiden mutation, mutation G20210A and in gene MTHFR) in patients underwent one or more vascular access thrombosis in comparison to control group without thrombosis. A case-control study was conducted of 127 hemodialysis patients to determine whether thrombophilia was associated with arteriovenous fistula thrombosis. Patients were tested for factor V Leiden, prothrombin gene mutation, methylenetetrahydrofolate reductase genotype, serum homocysteine. It is shown that the total plasma homocysteine level in patients undergoing dialysis is differed from healthy subjects (27,5 ± 9,34 vs 11,2 ± 3,54 µmol/l, p < 0,05), but similar to those in control and experimental groups (28,3 ± 5,1 vs 25,8 ± 6,3 µmol/l). Frequencies of mutations in research and control groups were as follows: Leiden mutation - 4,7 and 3,5%; mutation MTHFR heterozygotic - 28,6 and 31,7%, MTHFR homozygous 2,4 and 3,5%; mutation MTHFR heterozygotic + Leiden mutation of 2,4 and 3,5%, respectively. The conclusion. System risk factors of a venous thrombosis, such as level of tHcy and mutations of genes, do not affect the frequency of thrombosis of vascular access in patients on maintenance hemodialysis. Large, multicenter, prospective cohort studies are needed to confirm the observations from this case-control retrospective study.

заместительная почечная терапиясосудистый доступмутации геновтромбозы доступагипергомоциcтеинемияReferencesМойсюк Я.Г., Беляев А.Ю., Иноземцев А.С., Шило В.Ю. и соавт. Постоянный сосудистый доступ для гемодиализа: современные тенденции. Нефрология и диализ 2002; 4; 1: 14-24.Мойсюк Я.Г., Беляев А.Ю., Иноземцев А.С., Шило В.Ю. и соавт. Постоянный сосудистый доступ для гемодиализа: современные тенденции. Нефрология и диализ 2002; 4; 1: 14-24.Atac B., Yakupoglu U., Ozbek N. et al. Role of genetic mutations in vascular access thrombosis among hemodialysis patients waiting for renal transplantation. Transplant Proc 2002; 34: 2030-2032.Atac B., Yakupoglu U., Ozbek N. et al. Role of genetic mutations in vascular access thrombosis among hemodialysis patients waiting for renal transplantation. Transplant Proc 2002; 34: 2030-2032.Bay W.H., Henry M.L. et al. Predicting hemodialysis access failure with color flow Doppler ultrasound. Am J Nephrol 1998; 18 (4): 296-304.Bay W.H., Henry M.L. et al. Predicting hemodialysis access failure with color flow Doppler ultrasound. Am J Nephrol 1998; 18 (4): 296-304.Bostom A.G., Lathrop L. Hyperhomocysteinemia in end-stage renal disease: prevalence, etiology, and potential relationship with arteriosclerotic outcomes. Kidney International 1997; 52: 10-20.Bostom A.G., Lathrop L. Hyperhomocysteinemia in end-stage renal disease: prevalence, etiology, and potential relationship with arteriosclerotic outcomes. Kidney International 1997; 52: 10-20.Casserly L.F., Dember L.M. Thrombosis in end-stage renal disease. Semin Dial 2003; 16: 245-256.Casserly L.F., Dember L.M. Thrombosis in end-stage renal disease. Semin Dial 2003; 16: 245-256.Crowther M.A., Kelton J.G. Congenital thrombophilic states associated with venous thrombosis: A qualitative overview and proposed classification system. Ann Intern Med 2003; 138: 128-134.Crowther M.A., Kelton J.G. Congenital thrombophilic states associated with venous thrombosis: A qualitative overview and proposed classification system. Ann Intern Med 2003; 138: 128-134.De Stefano V., Chiusolo P., Paciaroni K. et al. Epidemiology of factor V Leiden: clinical implication Semin Thromb Haemost 1998; 24: 367-379.De Stefano V., Chiusolo P., Paciaroni K. et al. Epidemiology of factor V Leiden: clinical implication Semin Thromb Haemost 1998; 24: 367-379.Eikelboom J.W., Hankey G.J., Anand S.S. et al. Association between high homocysteine and ischemic stroke due to large- and small-artery disease but not other etiologic subtypes of ischemic stroke. Stroke 2000; 31: 1069-1075.Eikelboom J.W., Hankey G.J., Anand S.S. et al. Association between high homocysteine and ischemic stroke due to large- and small-artery disease but not other etiologic subtypes of ischemic stroke. Stroke 2000; 31: 1069-1075.Feldman H.I., Held P.J., Hutchinson J.T., Stoiber E., Hartigan M.F., Berlin J.A. Hemodialysis vascular access morbidity in the United States. Kidney Int 1993; 43: 1091-1096.Feldman H.I., Held P.J., Hutchinson J.T., Stoiber E., Hartigan M.F., Berlin J.A. Hemodialysis vascular access morbidity in the United States. Kidney Int 1993; 43: 1091-1096.Finkelstein J.D. Regulation of homocysteine metabolism. In: Carmel R., Jacobsen D.W. (eds.). Homocysteine in health and disease. NY: Cambridge University Press 2001: 92-99.Finkelstein J.D. Regulation of homocysteine metabolism. In: Carmel R., Jacobsen D.W. (eds.). Homocysteine in health and disease. NY: Cambridge University Press 2001: 92-99.Fodinger M., Mannhalter C., Pabinger I. et al. Resistance to activated protein C (APC): Mutation at ARG of coagulation factor V and vascular access thrombosis in hemodialysis patients. Nephrol Dial Transplant 1996; 11: 668-672.Fodinger M., Mannhalter C., Pabinger I. et al. Resistance to activated protein C (APC): Mutation at ARG of coagulation factor V and vascular access thrombosis in hemodialysis patients. Nephrol Dial Transplant 1996; 11: 668-672.Fukasawa M., Matsushita K., Kamiyama M. et al. The methylentetrahydrofolate reductase C677T point mutation is a risk factor for vascular access thrombosis in hemodialysis patients. Am J Kidney Dis 2003; 41: 637-642.Fukasawa M., Matsushita K., Kamiyama M. et al. The methylentetrahydrofolate reductase C677T point mutation is a risk factor for vascular access thrombosis in hemodialysis patients. Am J Kidney Dis 2003; 41: 637-642.Giles W.H., Croft J., Greenlund K.J. et al. Total homocysteine concentration and the likelihood of nonfatal stroke. Results from the Third National Health and Nutrition Examination Survey, 1988-1994. Stroke 1998; 29: 2473-2477.Giles W.H., Croft J., Greenlund K.J. et al. Total homocysteine concentration and the likelihood of nonfatal stroke. Results from the Third National Health and Nutrition Examination Survey, 1988-1994. Stroke 1998; 29: 2473-2477.Hernandez E., Praga M., Alamo C. et al. Lipoprotein(a) and vascular access survival in patients on chronic hemodialysis. Nephron 1996; 72: 145-149.Hernandez E., Praga M., Alamo C. et al. Lipoprotein(a) and vascular access survival in patients on chronic hemodialysis. Nephron 1996; 72: 145-149.Hojs R., Gorenjak M., Ekart R. et al. Homocysteine and vascular access thrombosis in hemodialysis patients. Ren Fail 2002; 24: 215-222.Hojs R., Gorenjak M., Ekart R. et al. Homocysteine and vascular access thrombosis in hemodialysis patients. Ren Fail 2002; 24: 215-222.Klerk M., Verhoef P., Clarke R. et al. MTHFR 677C→T polymorphysm and risk of coronary heart disease: a meta-analysis. JAMA 2002; 288: 2023-2031.Klerk M., Verhoef P., Clarke R. et al. MTHFR 677C→T polymorphysm and risk of coronary heart disease: a meta-analysis. JAMA 2002; 288: 2023-2031.Margaglione M., Brancaccio V., Giuliani N. et al. Increased risk for venous thrombosis in carriers of the prothrombin G→A gene variant. Ann Intern Med 1998; 129: 89-93.Margaglione M., Brancaccio V., Giuliani N. et al. Increased risk for venous thrombosis in carriers of the prothrombin G→A gene variant. Ann Intern Med 1998; 129: 89-93.Markus H.S., Ali N., Swaminathan R. et al. A common polymorphism in the methylenetetrahydrofolate reductase gene, homocysteine, and ischemic cerebrovascular disease. Stroke 1997; 28: 1739-1743.Markus H.S., Ali N., Swaminathan R. et al. A common polymorphism in the methylenetetrahydrofolate reductase gene, homocysteine, and ischemic cerebrovascular disease. Stroke 1997; 28: 1739-1743.Moist L.M., Churchill D.N., House A.A. et al. Regular monitoring of access flow compared with monitoring of venous pressure fails to improve graft survival. J Am Soc Nephrol 2003; 14: 2645-2653.Moist L.M., Churchill D.N., House A.A. et al. Regular monitoring of access flow compared with monitoring of venous pressure fails to improve graft survival. J Am Soc Nephrol 2003; 14: 2645-2653.Nygard O., Nordrehang J.E., Refsum H. et al. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 1997; 337: 230-236.Nygard O., Nordrehang J.E., Refsum H. et al. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 1997; 337: 230-236.O’Shea S.I., Lawson J.H., Reddan D. et al. Hypercoagulable states and antithrombotic strategies in recurrent vascular access site thrombosis. J Vasc Surg 2003; 38: 541-548.O’Shea S.I., Lawson J.H., Reddan D. et al. Hypercoagulable states and antithrombotic strategies in recurrent vascular access site thrombosis. J Vasc Surg 2003; 38: 541-548.Paulson W.D. Prediction of hemodialysis synthetic graft thrombosis: Can we identify factors that impair validity of the dysfunction hypothesis? Am J Kidney Dis 2000; 35: 973-975.Paulson W.D. Prediction of hemodialysis synthetic graft thrombosis: Can we identify factors that impair validity of the dysfunction hypothesis? Am J Kidney Dis 2000; 35: 973-975.Poort S.R., Rosendaal F.R., Reitsma P.H. et al. A common genetic variation in the 3’untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and and an increase in venous thrombosis. Blood 1996; 88: 3698-3703.Poort S.R., Rosendaal F.R., Reitsma P.H. et al. A common genetic variation in the 3’untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and and an increase in venous thrombosis. Blood 1996; 88: 3698-3703.Price D.T., Ridker P.M. Factor V Leiden mutation and the risks for thromboembolic disease: a clinical perspective. Ann Intern Med 1997; 127: 895-903.Price D.T., Ridker P.M. Factor V Leiden mutation and the risks for thromboembolic disease: a clinical perspective. Ann Intern Med 1997; 127: 895-903.Schwab S.J., Oliver M.J., Suhocki P., McCann R. Hemodialysis arteriovenous access: Detection of stenosis and response to treatment by vascular access blood flow. Kidney Int 2001; 59: 358-362.Schwab S.J., Oliver M.J., Suhocki P., McCann R. Hemodialysis arteriovenous access: Detection of stenosis and response to treatment by vascular access blood flow. Kidney Int 2001; 59: 358-362.Shemin D., Lapane K.L., Bausserman L. et al. Plasma total homocysteine and hemodialysis access thrombosis: A prospective study. J Am Soc Nephrol 1999; 10: 1095-1099.Shemin D., Lapane K.L., Bausserman L. et al. Plasma total homocysteine and hemodialysis access thrombosis: A prospective study. J Am Soc Nephrol 1999; 10: 1095-1099.Tamura T., Bergman S.M., Morgan S.L. Homocysteine, B vitamins and vascular-access thrombosis in patints treated with hemodialysis. Am J Kidney 1998; 32: 475-481.Tamura T., Bergman S.M., Morgan S.L. Homocysteine, B vitamins and vascular-access thrombosis in patints treated with hemodialysis. Am J Kidney 1998; 32: 475-481.Tessitore N., Mansueto G., Bedogna V. et al. A prospective controlled trial on effect of percutaneous transluminal angioplasty on functioning arteriovenous fistulae survival. J Am Soc Nephrol 2003; 14: 1623-1627.Tessitore N., Mansueto G., Bedogna V. et al. A prospective controlled trial on effect of percutaneous transluminal angioplasty on functioning arteriovenous fistulae survival. J Am Soc Nephrol 2003; 14: 1623-1627.Tosetto A., Rodeghiero F., Martinelli I. еt al. Additional genetic risk factors for venous thromboembolism in carriers of the factor V Leiden mutation. Br J Haematol 1998; 103: 871-876.Tosetto A., Rodeghiero F., Martinelli I. еt al. Additional genetic risk factors for venous thromboembolism in carriers of the factor V Leiden mutation. Br J Haematol 1998; 103: 871-876.Tripodi A., Chantarangkul V., Lombardi R. et al. Multicenter study of homocysteine measurement - performance characteristics of different methods, influence of standards on interlaboratory agreement of results. Thromb Haemost 2001; 85: 291-295.Tripodi A., Chantarangkul V., Lombardi R. et al. Multicenter study of homocysteine measurement - performance characteristics of different methods, influence of standards on interlaboratory agreement of results. Thromb Haemost 2001; 85: 291-295.Tripodi A., Mannucci P.M. Laboratory investigation of thrombophilia. Clin Chem 2001; 47: 1597-1606.Tripodi A., Mannucci P.M. Laboratory investigation of thrombophilia. Clin Chem 2001; 47: 1597-1606.Turmel-Rodrigues L., Pengloan J., Baudin S. et al. Treatment of stenosis and thrombosis in hemodialysis fistulas and grafts by interventional radiology. Nephrol Dial Transplant 2000; 15 (12): 2029-2036.Turmel-Rodrigues L., Pengloan J., Baudin S. et al. Treatment of stenosis and thrombosis in hemodialysis fistulas and grafts by interventional radiology. Nephrol Dial Transplant 2000; 15 (12): 2029-2036.USRDS. The economic cost of ESRD, vascular access procedures, and Medicare spending for alternative modalities of treatment. United States Renal Data System. Am J Kidney Dis 1997; 30 [Suppl 1]: S160-177.USRDS. The economic cost of ESRD, vascular access procedures, and Medicare spending for alternative modalities of treatment. United States Renal Data System. Am J Kidney Dis 1997; 30 [Suppl 1]: S160-177.Van Cott E.M., Laposata M. Laboratory evaluation of hypercoagulable states. Hematol Oncol Clin North Am 1998; 12: 1141-1166.Van Cott E.M., Laposata M. Laboratory evaluation of hypercoagulable states. Hematol Oncol Clin North Am 1998; 12: 1141-1166.Wuthrich R.P. Factor V Leiden mutation: potential thrombogenic role in renal vein, dialysis graft and transplant vascular thrombosis. Curr Opin Nephrol Hypertens. 2001; 10 (3): 409-414.Wuthrich R.P. Factor V Leiden mutation: potential thrombogenic role in renal vein, dialysis graft and transplant vascular thrombosis. Curr Opin Nephrol Hypertens. 2001; 10 (3): 409-414.

The authors declare that there are no conflicts of interest present.