References

nid

Нефрология и диализ

Nephrology and Dialysis

1680-44222618-9801

Российское диализное общество

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

nid-38

Research Article

ОБЗОРЫ И ЛЕКЦИИ

REVIEWS AND LECTURES

Нефротический синдром как фактор риска тромботических и тромбоэмболических осложнений

Nephrotic syndrome as a risk factor for thrombotic and thromboembolic complications

Носов

В. П.

Nosov

V. P.

noemail@neicon.ru

Соловьянова

Е. Н.

Solovyanova

E. N.

elenas-nn@mail.ru

Королева

Л. Ю.

Koroleva

L. Yu.

noemail@neicon.ru

ФГБОУ ВО «Приволжский исследовательский медицинский университет» Минздрава РФРоссияPrivolzhsky Research Medical UniversityRussian Federation

2021

21062024

233366378

2024

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

Nosov V.P., Solovyanova E.N., Koroleva L.Y.

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/38

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.

The multifactorial origin of thrombotic and thromboembolic complications in nephrotic syndrome (NS) is reviewed. In total, the primary and secondary NS increase the risk of developing venous and arterial thromboembolic complications by a factor of 8 in comparison with the 10-year general population risk. The most common are venous thrombosis (deep vein thrombosis, renal vein, vena cava inferior, portal vein, mesenteric and intracranial veins), while arterial thromboses with limb or brain damage are much more rare. In general, the development of thrombosis is much more often observed in adult patients with NS, the incidence of thromboembolism in them is 25%, while in children it is about 3%. Risk factors for the development of venous thrombotic complication (VTC) in patients with NS can be divided into traditional (modifiable and unmodifiable) and associated with NS. The modified ones include hospitalization, VTC in the past, prolonged immobilization (>3 days), therapeutic and diagnostic manipulations (central and peripheral venous catheters), acquired thrombophilia (antiphospholipid syndrome, hyperhomocysteinemia), autoimmune glomerulopathy, malign neoplasms, obesity. Unmodified factors include old age and hereditary thrombophilia. NS can be combined with genetic markers of thrombophilia (factor V Leiden (G1691A), factor II (G20210A), plasminogen activator inhibitor-1 (PAI, 4G/ 4G, 4G/5G), folate cycle enzymes - methylenetetrahydrofolate reductase (MTHFR) genes mutations). However, the number of studies is limited and the results are conflicting. This underlies the ongoing discussion about the need to screen these markers in patients with NS. Risk factors for VTC associated with NS include hypohydration, acute kidney injury, use of diuretics and glucocorticosteroids. The preventive therapy of thrombotic and thromboembolic complications of NS is rather difficult, it is based on the assessment of the “benefit-risk” balance: a decrease in the risk of thrombotic events in assessing the risk of hemorrhagic complications.

нефротический синдромвенозные тромботические осложненияnephrotic syndromevenous thrombotic complications

References1

Нефрология. Клинические рекомендации. Под. ред. Е.М. Шилова, А.В. Смирнова, Н.Л. Козловской.- М.: ГЭОТАР-Медиа, 2016. 816с.

Nishi S, Ubara Y, Utsunomiya Y, et al. Evidence-based clinical practice guidelines for nephrotic syndrome. Clin Exp Nephrol. 2014;20 (3):342-370.

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.

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.

AlYousef A, AlSahow A, AlHelal B, et al. Glomerulonephritis histopathological pattern change. BMC Nephrol. 2020;21(1):186.

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.

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.

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.

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.

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.

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.

Боброва Л.А., Козловская Н.Л. Тромбоэмболические осложнения нефротического синдрома. Терапевтический архив. 2020; 92 (6): 105-116.

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.

Glassock RJ. Prophylactic anticoagulation in nephrotic syndrome: A clinical conundrum. J Am Soc Nephrol. 2007;18(8):2221-2225.

Rayer P. Traité des maladies des reins et des altérations de la sécrétion urinaire. Paris: J.-B. Bailliére, 1839-1841.

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.

Козловская Н.Л., Боброва Л.А. Тромбоз почечных вен. Клиническая нефрология. 2012;1:4-9.

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.

Fahal IH, McClelland P, Hay CRM, Bell GM. Arterial thrombosis in the nephrotic syndrome. Postgrad Med J. 1994;70(830):905-909.

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.

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.

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.

Khanna A. Undiagnosed and unsuspected nephrotic syndrome in a young adult presenting as submassive pulmonary embolism. Chest. 2016;149(4):A506.

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.

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.

Kayali F, Najjar R, Aswad F, et al. Venous thromboembolism in patients hospitalized with nephrotic syndrome. Am J Med. 2008;121(3):226-230.

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.

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.

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.

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.

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.

Ageno W, Squizzato A, Garcia D, Imberti D. Epidemiology and risk factors of venous thromboembolism. Semin. Thromb. Hemost. 2006;32(7):651-658.

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.

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.

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.

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.

Gordon-Cappitelli J, Choi MJ. Prophylactic anticoagulation in adult patients with nephrotic syndrome. Clin J Am Soc Nephrol. 2020;15(1):123-125.

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)

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.

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.

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.

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.

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.

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)

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.

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.

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.

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.

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.

Donnellan E, Khorana AA. Cancer and venous thromboembolic disease: a review. Oncology 2017;22(2):199-207.

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.

Beyan C. Methylenetetrahydrofolate reductase gene polymorphisms in patients with nephrotic syndrome. Clin. Nephrol. 2013;80(4):311.

Menon S. Acute kidney injury in nephrotic syndrome. Front Pediatr. 2019;6:428.

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.

Loscalzo J. Venous thrombosis in the nephrotic syndrome. N Engl J Med. 2013;368(10): 956-958.

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.

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.

Mazhar HR, Aeddula NR. Renal vein thrombosis. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020.

Yang GF, Schoepf UJ, Zhu H, et al. Thromboembolic complications in nephrotic syndrome: imaging spectrum. Acta Radiol. 2012;53(10):1186-1194.

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.

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).

Pincus KJ, Hynicka LM. Prophylaxis of thromboembolic events in patients with nephrotic syndrome. Ann Pharmacother. 2013;47(5):725-734.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Wei MY, Ward SM. The anti-factor Xa range for low molecular weight heparin thromboprophylaxis. Hematol Rep. 2015;7(4):5844.

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]

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.

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.

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.

Dupree LH, Reddy P. Use of rivaroxaban in a patient with history of nephrotic syndrome and hypercoagulability. Ann Pharmacother. 2014;48(12):1655-1658.

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.

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.

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.

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