Российское диализное общество

Просмотр статьи

<< Вернуться к списку статей журнала

Том 23 №3 2021 год - Нефрология и диализ

Нефротический синдром как фактор риска тромботических и тромбоэмболических осложнений


Носов В.П. Соловьянова Е.Н. Королева Л.Ю.

DOI: 10.28996/2618-9801-2021-3-366-378

Аннотация: В обзоре дано представление о многофакторном происхождении тромботических и тромбоэмболических осложнений при нефротическом синдроме (НС). В сумме первичный и вторичный НС в 8 раз повышает риск развития венозных и артериальных тромбоэмболических осложнений в сравнении с 10-летним общепопуляционным риском. Наиболее часто в клинической практике встречаются венозные тромбозы (глубоких вен нижних конечностей, почечной и/или нижней полой, воротной вены, мезентериальных и интракраниальных вен), в то время как артериальные тромбозы с поражением конечностей или головного мозга наблюдаются гораздо реже. В целом развитие тромбозов значительно чаще отмечается у взрослых больных с НС, частота развития тромбоэмболий составляет у них 25%, тогда как у детей - около 3%. Факторы риска развития ВТО (венозных тромботических осложнений) у больных НС можно разделить на традиционные (модифицируемые и немодифицируемые) и связанные с НС. К модифицируемым следует отнести госпитализацию, ранее перенесенные ВТО, длительную иммобилизацию (>3 суток), лечебно-диагностические манипуляции (центральные и периферические венозные катетеры), приобретенные тромбофилии (антифосфолипидный синдром, гипергомоцистеинемия), аутоиммунные гломерулопатии, злокачественные новообразования, ожирение, прием оральных контрацептивов. К немодифицируемым факторам относятся пожилой возраст и наследственные тромбофилии. НС может сочетаться с генетическими маркерами тромбофилии (мутации генов фактора V - Leiden, G1691A), фактора II (G20210A), ингибитора активатора плазминогена-1 (PAI, 4G/4G, 4G/5G), ферментов фолатного цикла - метилен тетрагидрофолатредуктаза, MTHFR), однако количество исследований ограничено, а результаты противоречивы. Это лежит в основе сохраняющейся дискуссии о необходимости скрининга данных маркеров у больных НС. К факторам риска ВТО, обусловленным НС, относится гипогидратация, острое почечное повреждение, использование диуретиков и глюкокортикостероидов. Подчеркивается, что подходы к профилактической терапии тромботических и тромбоэмболических осложнений НС достаточно трудны, в основе их лежит оценка баланса «польза-риск»: снижение риска тромботических событий при оценке риска геморрагических осложнений.

Для цитирования: Носов В.П., Соловьянова Е.Н., Королева Л.Ю. Нефротический синдром как фактор риска тромботических и тромбоэмболических осложнений. Нефрология и диализ. 2021. 23(3):255-436. doi: 10.28996/2618-9801-2021-3-366-378


Весь текст

Ключевые слова: нефротический синдром, венозные тромботические осложнения, nephrotic syndrome, venous thrombotic complications

Список литературы:
  1. Нефрология. Клинические рекомендации. Под. ред. Е.М. Шилова, А.В. Смирнова, Н.Л. Козловской.- М.: ГЭОТАР-Медиа, 2016. 816с.
  2. Nishi S, Ubara Y, Utsunomiya Y, et al. Evidence-based clinical practice guidelines for nephrotic syndrome. Clin Exp Nephrol. 2014;20 (3):342-370.
  3. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1-150.
  4. Stoycheff N, Stevens LA, Schmid CH, et al. Nephrotic syndrome in diabetic kidney disease: an evaluation and update of the definition. Am J Kidney Dis. 2009;54(5):840-849.
  5. AlYousef A, AlSahow A, AlHelal B, et al. Glomerulonephritis histopathological pattern change. BMC Nephrol. 2020;21(1):186.
  6. Qureshi M, Alabi F, Christian F, Romero C. The forgotten urinalysis: an integral part of unmasking thrombophilia. J Community Hosp Intern Med Perspect. 2019;9(1):40-44.
  7. Practical hemostasis and thrombosis / edited by NS. Key, M. Makris, D. Lillicrap. - 3rd ed. - Chichester, West Sussex; Hoboken, NJ: John Wiley & Sons Inc., 2017:477 p.
  8. Kerlin BA, Ayoob R, Smoyer WE. Epidemiology and pathophysiology of nephrotic syndrome - associated thromboembolic disease. Clin J Am Soc Nephrol. 2012;7(3):513-520.
  9. Al Azzawi HF, Obi OC, Safi J, et al. Nephrotic syndrome-induced thromboembolism in adults. Int J Crit Illn Inj Sci. 2016;6(2):85-88.
  10. Christiansen CF, Schmidt M, Lamberg AL et al. Kidney disease and risk of venous thromboembolism: a nationwide population-based case-control study. J Thromb Haemost 2014;12(9):1449-1454.
  11. Medjeral-Thomas N, Ziaj S, Condon M, et al. Retrospective analysis of a novel regimen for the prevention of venous thromboembolism in nephrotic syndrome. Clin J Am Soc Nephrol. 2014;9(3):478-483.
  12. Боброва Л.А., Козловская Н.Л. Тромбоэмболические осложнения нефротического синдрома. Терапевтический архив. 2020; 92 (6): 105-116.
  13. Barbour SJ, Greenwald A, Djurdjev O, et al. Disease-specific risk of venous thromboembolic events is increased in idiopathic glomerulonephritis. Kidney Int. 2012; 81(2):190-195.
  14. Glassock RJ. Prophylactic anticoagulation in nephrotic syndrome: A clinical conundrum. J Am Soc Nephrol. 2007;18(8):2221-2225.
  15. Rayer P. Traité des maladies des reins et des altérations de la sécrétion urinaire. Paris: J.-B. Bailliére, 1839-1841.
  16. Ismail G, Obrişcă B, Jurubiţă R, et al. Inherited risk factors of thromboembolic events in patients with primary nephrotic syndrome. Medicina (Kaunas). 2020;56(5):242. doi: 10.3390/medicina56050242.
  17. Козловская Н.Л., Боброва Л.А. Тромбоз почечных вен. Клиническая нефрология. 2012;1:4-9.
  18. Wang YC, Chuang FR, Lee WC, et al. Low-molecular-weight heparin successfully used to treat a nephrotic patient complicated by superior mesenteric vein thrombosis and portal vein thrombosis. Med Princ Pract. 2011;20(2):196-199.
  19. Fahal IH, McClelland P, Hay CRM, Bell GM. Arterial thrombosis in the nephrotic syndrome. Postgrad Med J. 1994;70(830):905-909.
  20. Mahmoodi BK, ten Kate MK, Waanders F, et al. High absolute risks and predictors of venous and arterial thromboembolic events in patients with nephrotic syndrome: results from a large retrospective cohort study. Circulation 2008;117(2):224-230.
  21. Pallavi R, Sunggeun L, Baumstein D, Mendoza RC, Chaudhari A. Stroke in a young woman as a presenting manifestation of membranous nephropathy. Am J Ther. 2016;23(3):e950-954.
  22. Mirrakhimov AE, Ali AM, Barbaryan A, Prueksaritanond S, Hussain N. Primary nephrotic syndrome in adults as a risk factor for pulmonary embolism: an up-to-date review of the literature. Int J Nephrol. 2014;2014:916760.
  23. Khanna A. Undiagnosed and unsuspected nephrotic syndrome in a young adult presenting as submassive pulmonary embolism. Chest. 2016;149(4):A506.
  24. Rankin AJ, McQuarrie EP, Fox JG, Geddes CC, MacKinnon B, Scottish Renal Biopsy R. Venous thromboembolism in primary nephrotic syndrome - is the risk high enough to justify prophylactic anticoagulation? Nephron. 2017;135(1):39-45.
  25. Li S-J, Guo J-Z, Zuo K, et al. Thromboembolic complications in membranous nephropathy patients with nephrotic syndrome - a prospective study. Thromb Res. 2012;130(3):501-505.
  26. Kayali F, Najjar R, Aswad F, et al. Venous thromboembolism in patients hospitalized with nephrotic syndrome. Am J Med. 2008;121(3):226-230.
  27. Bakhtawar K, Mahmoodi B. High absolute risks and predictors of venous and arterial thromboembolic events in patients with nephrotic syndrome: results from a large retrospective cohort study. Circulation. 2008;117(2):224-30.
  28. Lionaki S, Derebail VK, Hogan SL, et al. Venous thromboembolism in patients with membranous nephropathy. Clin J Am Soc Nephrol. 2012;7(1):43-51.
  29. Mercadal L, Montcel ST, Nochy D, et al. Factors affecting outcome and prognosis in membranous lupus nephropathy. Nephrol Dial Transplant. 2002;17(10):1771-1778.
  30. Maas RJ, Deegens JK, Beukhof JR, et al. The clinical course of minimal change nephrotic syndrome with onset in adulthood or late adolescence: A case series. Am J Kidney Dis. 2017;69(5):637-646.
  31. Fenton A, Smith SW, Hewins P. Adult minimal-change disease: observational data from a UK centre on patient characteristics, therapies, and outcomes. BMC Nephrol. 2018;19(1):207.
  32. Ageno W, Squizzato A, Garcia D, Imberti D. Epidemiology and risk factors of venous thromboembolism. Semin. Thromb. Hemost. 2006;32(7):651-658.
  33. Gyamlani G, Molnar MZ, Lu JL, et al. Association of serum albumin level and venous thromboembolic events in a large cohort of patients with nephrotic syndrome. Nephrol Dial Transplant 2017;32(1):157-164.
  34. Yang Y, Lv J, Zhou F, et al. Risk factors of pulmonary thrombosis/embolism in nephrotic syndrome. Am J Med Sci. 2014;348(5):394-398.
  35. Kumar S, Chapagain A, Nitsch D, et al. Proteinuria and hypoalbuminemia are risk factors for thromboembolic events in patients with idiopathic membranous nephropathy: an observational study. BMC Nephrol 2012;13(1):107.
  36. Ismail G, Mircescu G, Ditoiu AV, et al. Risk factors for predicting venous thromboembolism in patients with nephrotic syndrome: focus on hemostasis-related parameters. Int Urol Nephrol. 2014;46(4):787-792.
  37. Gordon-Cappitelli J, Choi MJ. Prophylactic anticoagulation in adult patients with nephrotic syndrome. Clin J Am Soc Nephrol. 2020;15(1):123-125.
  38. Shinkawa K, Yoshida S, Seki T, Yanagita M, Kawakami K. Risk factors of venous thromboembolism in patients with nephrotic syndrome: a retrospective cohort study. Nephrol Dial Transplant. 2020; 1-8. doi:10.1093/ndt/gfaa134 (https://doi.org/10.1093/ndt/gfaa134)
  39. Lin R, McDonald G, Jolly T, Batten A, Chacko B. A systematic review of prophylactic anticoagulation in nephrotic syndrome. Kidney Int Rep. 2019;5(4):435-447.
  40. Zhang LJ, Zhang Z, Li SJ, et al. Pulmonary embolism and renal vein thrombosis in patients with nephrotic syndrome: prospective evaluation of prevalence and risk factors with CT. Radiology. 2014;273(3):897-906.
  41. Harza M, Ismail G, Mitroi G, et al. Histological diagnosis and risk of renal vein thrombosis and other thrombotic complications in primitive nephrotic syndrome. Rom J Morphol Embryol. 2013;54(3):555-560.
  42. Iwaki H, Neshige S, Hara N, et al. Cerebral venous thrombosis as a complication of nephrotic syndrome - a case report and literature review. Rinsho Shinkeigaku. 2014;54(6):495-501.
  43. Nakayama T, Mitsuno R, Torimitsu T, et al. Difficulty in managing nephrotic syndrome-associated cerebral venous thrombosis. CEN Case Rep. 2021;10(1):132-138.
  44. Downie E, Diep J, Sungala N, Wong J. IgM nephropathy complicated by cerebral venous sinus thrombosis: a case study. BMC Nephrol. 2020; 21(1):390. doi:10.1186/s12882-020-02048-5 (https://doi.org/10.1186/s12882-020-02048-5)
  45. Lee T, Derebail VK, Kshirsagar AV, et al. Patients with primary membranous nephropathy are at high risk of cardiovascular events. Kidney Int. 2016;89(5):1111-1118.
  46. Zou PM, Li H, Cai JF, et al. A cohort study of incidences and risk factors for thromboembolic events in patients with idiopathic membranous nephropathy. Chin Med Sci J. 2018;33(2):91-99.
  47. Floege J, Barbour SJ, Cattran DC, et al. Management and treatment of glomerular diseases (part 1): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2019;95(2):268-280.
  48. Huang MJ, Wei RB, Wang ZC, et al. Mechanisms of hypercoagulability in nephrotic syndrome associated with membranous nephropathy as assessed by thromboelastography. Thromb. Res. 2015;136(3):663-668.
  49. Garcia Moreira V, Beridze Vaktangova N, Martinez Gago MD, et al. Overestimation of albumin measured by bromocresol green vs bromocresol purple method: Influence of acute-phase globulins. Lab Med. 2018;49(4):355-361.
  50. Donnellan E, Khorana AA. Cancer and venous thromboembolic disease: a review. Oncology 2017;22(2):199-207.
  51. Sahin M, Ozkurt S, Degirmenci NA, et al. Assessment of genetic risk factors for thromboembolic complications in adults with idiopathic nephrotic syndrome. Clin Nephrol. 2013;79(6):454-462.
  52. Beyan C. Methylenetetrahydrofolate reductase gene polymorphisms in patients with nephrotic syndrome. Clin. Nephrol. 2013;80(4):311.
  53. Menon S. Acute kidney injury in nephrotic syndrome. Front Pediatr. 2019;6:428.
  54. Johannesdottir SA, Horváth-Puhó E, Dekkers OM, et al. Use of glucocorticoids and risk of venous thromboembolism: a nationwide population-based case-control study. JAMA Intern Med. 2013;173(9):743-52.
  55. Loscalzo J. Venous thrombosis in the nephrotic syndrome. N Engl J Med. 2013;368(10): 956-958.
  56. Li S-J, Tu YM, Zhou CS, et al. Risk factors of venous thromboembolism in focal segmental glomerulosclerosis with nephrotic syndrome. Clin Exp Nephrol. 2016;20(2):212-217.
  57. Stevens SM, Woller SC, Bauer K, et al. Guidance for the evaluation and treatment of hereditary and acquired thrombophilia. J Thromb Thrombolysis. 2016;41(1):154-164.
  58. Mazhar HR, Aeddula NR. Renal vein thrombosis. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020.
  59. Yang GF, Schoepf UJ, Zhu H, et al. Thromboembolic complications in nephrotic syndrome: imaging spectrum. Acta Radiol. 2012;53(10):1186-1194.
  60. Rostoker G, Durand-Zaleski I, Petit-Phar M, et al. Prevention of thrombotic complications of the nephrotic syndrome by the low-molecular-weight heparin enoxaparin. Nephron. 1995;69(1):20-28.
  61. Kelddal S, Nykjær KM, Gregersen JW, Birn H. Prophylactic anticoagulation in nephrotic syndrome prevents thromboembolic complications. BMC Nephrol. 2019; 20(1):139. doi:10.1186/s12882-019-1336-8 (https://doi.org/10.1186/s12882-019-1336-8).
  62. Pincus KJ, Hynicka LM. Prophylaxis of thromboembolic events in patients with nephrotic syndrome. Ann Pharmacother. 2013;47(5):725-734.
  63. Cattran DC, Feehally J, Cook HT, et al. Kidney disease: Improving global outcomes (KDIGO) glomerulonephritis work group. KDIGO clinical practice guideline for glomerulonephritis. Kidney Int. 2012; Suppl 2: 139-274.
  64. Beck L, Bomback AS, Choi MJ, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for glomerulonephritis. Am J Kidney Dis. 2013;62(3):403-441.
  65. Смирнов А.В., Добронравов В.А., Сиповский В.Г. и др. Клинические рекомендации по диагностике, лечению и прогнозу болезни минимальных изменений у взрослых. Нефрология.2014;18(4):68-92.
  66. Kalaitzidis RG, Duni A, Liapis G, et al. Anticoagulant-related nephropathy: a case report and review of the literature of an increasingly recognized entity. Int Urol Nephrol. 2017; 49(8):1401-1407.
  67. Fang MC, Go AS, Chang Y, et al. A new risk scheme to predict warfarin-associated hemorrhage: The ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) Study. J Am Coll Cardiol. 2011;58(4):395-401.
  68. Pisters R, Lane DA, Nieuwlaat R, et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093-1100.
  69. Klok FA, Kooiman J, Huisman MV, Konstantinides S, Lankeit M. Predicting anticoagulant-related bleeding in patients with venous thromboembolism: a clinically oriented review. Eur Respir J. 2015;45(1):201-210.
  70. Lee T, Biddle AK, Lionaki S, et al. Personalized prophylactic anticoagulation decision analysis in patients with membranous nephropathy. Kidney Int. 2014;85(6):1412-1420.
  71. Nachman P, Reich HN. Prophylactic anticoagulation in patients with membranous nephropathy: A decision analysis. University of North Carolina School of Medicine website. https://www.med.unc.edu/gntools/index.html. Accessed February 01, 2021.
  72. Reinecke H, Engelbertz C, Schabitz WR. Preventing stroke in patients with chronic kidney disease and atrial fibrillation: benefit and risks of old and new oral anticoagulants. Stroke 2013;44(10):2935-2941.
  73. Basu A, Jain S, Patel D, et al. Failure of anticoagulation in a case of nephrotic syndrome with recurrent thromboembolism. Chest. 2015;148(4):983A.
  74. Sexton DJ, de Freitas DG, Little MA, et al. Direct-acting oral anticoagulants as prophylaxis against thromboembolism in the nephrotic syndrome. Kidney Int Rep. 2018;3(4):784-793.
  75. Radhakrishnan J, Glassock RJ, Rovin BH, Lam AQ. Hypercoagulability in nephrotic syndrome.UptoDate2020. https://www.uptodate.com/contents/image?imageKey=NEPH%2F121272&topicKey=NEPH%2F3043&search=nephrotic%20syndrome,%20thrombosis&rank=1~150&source=see_link. Accessed February 01, 2021.
  76. Resh M, Mahmoodi BK, Navis GJ, et al. Statin use in patients with nephrotic syndrome is associated with a lower risk of venous thromboembolism. Thromb Res. 2011;127(5): 395-399.
  77. Hofstra JM, Wetzels JFM. Should aspirin be used for primary prevention of thrombotic events in patients with membranous nephropathy? Kidney Int. 2016;89(5):981-983.
  78. Wagoner RD, Stanson AW, Holley KE, et al. Renal vein thrombosis in idiopathic membranous glomerulopathy and nephrotic syndrome: incidence and significance. Kidney Int. 1983;23(2):368-374.
  79. Wei MY, Ward SM. The anti-factor Xa range for low molecular weight heparin thromboprophylaxis. Hematol Rep. 2015;7(4):5844.
  80. Ghaly P, Iliopoulos J, Ahmad M. Acute bilateral renal vein thrombosis diagnosis and management: a case report. J Surg Case Rep. 2020; 2020(8):rjaa238. [39]
  81. Li Y, Chen Y, Qi X, et al. Poor response to rivaroxaban in nephrotic syndrome with acute deep vein thrombosis: A case report. Medicine. 2019;98(31):e16585.
  82. Han T, Han C, Thet Z. Warfarin vs new oral anticoagulant in primary adult nephrotic syndrome associated venous thromboembolism. Nephrol. 2017;22(Suppl 3):64.
  83. Reynolds ML, Nachman PH, Mooberry MJ, Crona DJ, Derebail VK. Recurrent venous thromboembolism in primary membranous nephropathy despite direct Xa inhibitor therapy. J Nephrol. 2019;32(4):669-672.
  84. Dupree LH, Reddy P. Use of rivaroxaban in a patient with history of nephrotic syndrome and hypercoagulability. Ann Pharmacother. 2014;48(12):1655-1658.
  85. Shimada Y, Nagaba Y, Nagaba H, et al. Edoxaban was effective for treating renal vein thrombosis in a patient with nephrotic syndrome. Intern Med. 2017;56(17):2307-2310.
  86. Sasaki Y, Raita Y, Uehara G, Higa Y, Miyasato H. Carotid thromboembolism associated with nephrotic syndrome treated with dabigatran. Case Rep Nephrol Urol. 2014;4(1):42-52.
  87. Zhang L, Zhang H, Zhang J, et al. Rivaroxaban for the treatment of venous thromboembolism in patients with nephrotic syndrome and low AT-III: A pilot study. Exp Ther Med. 2018;15(1):739-744.

Другие статьи по теме


Навигация по статьям
Разделы журнала
Наиболее читаемые статьи
Журнал "Нефрология и диализ"