Thromboembolic complications in nephrotic syndrome

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Abstract


This review devoted to the nephrotic syndrome (NS) subsequent thrombotic outcomes. The pathogenesis of hypercoagulation disorders that cause venous and arterial vascular system thrombosis are studied. Discussed procoagulant and anticoagulant mechanisms imbalance due to the anticoagulants natural urinal loss, affected by disfunction of the glomerular filter selective permeability, leading to high molecular weight liver-derived proteins (at least of the albumin size) leakage, fibrinolysis depression, excessive liver synthesis of plasma clotting cascade factors and platelet activation. Presented new data on the thrombogenesis at NS concerning the role of endothelial microparticles with high prothrombogenic activity that go from damaged glomerulus endothelial capillary cells into the systemic circulation, which can turn the local renal hypercoagulation (concomitant to the kidney immune inflammation process) into the generalized, working towards the thrombosis development. The most frequent adverse variants of arterial and venous thromboses are studied, specified their basic and general risk factors, as well as individual, varying in different patients. Indications and prophylactic anticoagulant therapy regimen and thrombosis treatment duration in patients with NS are discussed. It also stressed that the decision on time and method of anticoagulant therapy for a NS patients is still a challenge for healthcare providers.


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About the authors

Larisa A. Bobrova

Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
Email: mrlee2005@yandex.ru
ORCID iD: 0000-0001-6265-4091

Russian Federation, Moscow

к.м.н., ассистент каф. внутренних, профессиональных болезней и ревматологии

Natalia L. Kozlovskaya

People’s Friendship University of Russia; Yeramishantsev City Clinical Hospital

Email: mrlee2005@yandex.ru
ORCID iD: 0000-0002-4275-0315

Russian Federation, Moscow

д.м.н., проф., каф. внутренних болезней с курсами кардиологии и функциональной диагностики, рук. Центра помощи беременным женщинам с патологией почек 

References

  1. Нефрология. Под. ред. Е.М. Шилова М.: ГЭОТАР-Медиа, 2010 [Nefrologija. Pod. red. E.M. Shilova. Moscow: GEOTAR-Media, 2010 (In Russ.)].
  2. Mahmoodi B, ten Kate M, Waanders F, et al. High Absolute Risks and Predictors of Venous and Arterial Thromboembolic Events in Patients With Nephrotic Syndrome. Circulation. 2008;117(2):224-30. doi: 10.1161/circulationaha.107.716951
  3. Козловская Н.Л., Боброва Л.А. Тромбоз почечных вен. Клиническая нефрология. 2012;1:4-9 [Kozlovskaya NL, Bobrova LA. Renal vein thrombosis. Clinical Nephrology. 2012;1:4-9 (In Russ.)]. https://lib.medvestnik.ru/articles/Tromboz-pochechnyh-ven.html
  4. Lempp S, Schwenger V. Isolated right ventricular thrombus in an adult patient with nephrotic syndrome: a case report. J Med Case Rep. 2017;11(1):311. doi: 10.1186/s13256-017-1491-0
  5. Al-Azzawi H, Obi O, Safi J, Song M. Nephrotic syndrome-induced thromboembolism in adults. Int J Crit Illn Inj Sci. 2016;6(2):85. doi: 10.4103/2229-5151.183019
  6. Rayer P. Traite des maladies des reins et des alteret lens de la secretions urinaire. Baillieve. 1840;2:550-9.
  7. Kitchens C, Kessler C, Konkle B. Consultative Hemostasis And Thrombosis. Philadelphia, PA: Elsevier/Saunders; 2013. doi: 10.1016/C2009-0-64563-3
  8. Welch T. Nephrosis and clots. J Pediatr. 2009;155(1):A2. doi: 10.1016/j.jpeds.2009.05.021
  9. Cameron JS. Five hundred years of the nephrotic syndrome: 1484–1984. Ulster Med J. 1985;54(Suppl.):S5-S19. PMID: 3909583.
  10. Lin R, Mcdonald G, Jolly T, Batten A. A Systematic Review of Prophylactic Anticoagulation in Nephrotic Syndrome. Kidney Int Reports. 2020. doi: 10.1016/j.ekir.2019.12.001
  11. Tavil B, Kara F, Topaloglu R, et al. Case series of thromboembolic complications in childhood nephrotic syndrome: Hacettepe experience. Clin Exp Nephrol. 2015;19(3):506-13. doi: 10.1007/s10157-014-1005-y
  12. Pallavi R, Sunggeun L, Baumstein D, et al. Stroke in a Young Woman as a Presenting Manifestation of Membranous Nephropathy. Am J Ther. 2016;23(3):e950-e954. doi: 10.1097/mjt.0000000000000075
  13. Khanna A. Undiagnosed and Unsuspected Nephrotic Syndrome in a Young Adult Presenting as Submassive Pulmonary Embolism. Chest. 2016;149(4):A506. doi: 10.1016/j.chest.2016.02.528
  14. Qureshi M, Alabi F, Christian F, Romero C. The forgotten urinalysis: an integral part of unmasking thrombophilia. J Commun Hosp Int Med Perspect. 2019;9(1):40-4. doi: 10.1080/20009666.2018.1562854
  15. Козловская Н.Л. Низкомолекулярные гепарины в практике нефролога. Клиническая нефрология. 2011;1:15-22 [Kozlovskaya NL. Low molecular weight heparins in nephrologists practice. Clinical Nephrology. 2011;1:15-22 (In Russ.)]. https://lib.medvestnik.ru/articles/Nizkomolekulyarnye-gepariny-v-praktike-nefrologa.html
  16. Kerlin B, Blatt N, Fuh B, et al. Epidemiology and Risk Factors for Thromboembolic Complications of Childhood Nephrotic Syndrome: A Midwest Pediatric Nephrology Consortium (MWPNC) Study. J Pediatr. 2009;155(1):105-10.e1. doi: 10.1016/j.jpeds.2009.01.070
  17. Kerlin BA, Ayoob R, Smoyer WE. Epidemiology and Pathophysiology of Nephrotic Syndrome–Associated Thromboembolic Disease. Clin J Am Soc Nephrol. 2012;7(3):513-20. doi: 10.2215/CJN.10131011
  18. Singhal R, Brimble KS. Thromboembolic complications in the nephrotic syndrome: Pathophysiology and clinical management. Thromb Res. 2006;118(3):397-407. doi: 10.1016/j.thromres.2005.03.030
  19. Llach F, Papper S, Massry S. The clinical spectrum of renal vein thrombosis: Acute and chronic. Am J Med. 1980;69(6):819-27. doi: 10.1016/s0002-9343(80)80006-4
  20. Zhang L, Zhang Z, Li S, 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. doi: 10.1148/radiol.14140121
  21. Wright J, Watts R. Venous Thromboembolism in Pediatric Patients. J Pediatr Hematol Oncol. 2011;33(4):261-4. doi: 10.1097/mph.0b013e3182134111
  22. Andrew M, Monagle P, Brooker L. Thromboembolic Complications During Infancy And Childhood. Hamilton, Ont. B.C. Decker; 2000.
  23. Raffini L, Huang Y, Witmer C, Feudtner C. Dramatic Increase in Venous Thromboembolism in Children’s Hospitals in the United States From 2001 to 2007. Pediatrics. 2009;124(4):1001-8. doi: 10.1542/peds.2009-0768
  24. Сулимов В.А., Беленцов С.М., Головина Н.И. и др. Российские данные международного регистра ENDORSE, посвященного выявлению больных с риском тромбоза глубоких вен в стационарах, располагающих возможностями оказания экстренной медицинской помощи. Рациональная Фармакотерапия в Кардиологии. 2008;4(3):6-16 [Sulimov VA, Belentsov SM, Golovina NI, et al. The Russian data of international ENDORSE REGISTER (Epidemiologic International Day for the Evaluation of Patients at Risk of Venous Thrombosis in Acute Hospital Care Setting). Rational Pharmacotherapy in Cardiology. 2008;4(3):6-16 (In Russ.)]. doi: 10.20996/1819-6446-2008-4-3-6-16
  25. Chung S, Park CW, Chang YS. Renal infarction and rapidly progressive arterial thromboembolism following a percutaneous renal biopsy. BMJ Case Rep. 2009. doi: 10.1136/bcr.06.2009.1930
  26. Remuzzi G, Mecca G, Marchesi D, et al. Platelet hyperaggregability and the nephrotic syndrome. Thromb Res. 1979;16(3-4):345-54. doi: 10.1016/0049-3848(79)90082-3
  27. Sirolli V, Ballone E, Garofalo D, et al. Platelet Activation Markers in Patients with Nephrotic Syndrome. Nephron. 2002;91(3):424-30. doi: 10.1159/000064282
  28. Llach F. Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome. Kidney Int. 1985;28. doi: 10.1038/ki.1985.149
  29. Ozanne P, Francis RB, Meiselman HJ. Red blood cell aggregation in nephrotic syndrome. Kidney Int. 1983;23(3):519-25. doi: 10.1038/ki.1983.50
  30. Zwaginga JJ, Koomans HA, Sixma JJ, Rabelink TJ. Thrombus formation and platelet-vessel wall interaction in the nephrotic syndrome under flow conditions. J Clin Invest. 1994;93(1):204-11. doi: 10.1172/JCI116947
  31. Козловская Н.Л., Медведева Т.Ю., Мирошниченко Н.Г., Кама- лов Ю.Р. Тромбоз почечных вен при мембранозной нефропатии. Терапевтический архив. 2000;72(6):71-3 [Kozlovskaia NL, Medvede- va TIu, Miroshnichenko NG, Kamalov IuR. Renal vein thrombosis in membranous nephropathy (case report and review of literature). Therapeutic Archive. 2000;72(6):71-3 (In Russ.)].
  32. Comp PC, Doray D, Patton D, Esmon CT. An Abnormal Plasma Distribution of Protein S Occurs in Functional Protein S Deficiency. Vol 67; 1986. www.bloodjournal.org
  33. Al-Mugeiren MM, Abdel Gader AGM, Al-Rasheed SA, Al-Salloum AA. Tissue factor pathway inhibitor in childhood nephrotic syndrome. Pediatr Nephrol. 2006;21(6):771-7. doi: 10.1007/s00467-006-0061-2
  34. Loscalzo J. Venous thrombosis in the nephrotic syndrome. N Engl J Med. 2013;368(10):956-8. doi: 10.1056/NEJMcibr1209459
  35. Svenningsen P, Bistrup C, Friis U, et al. Plasmin in Nephrotic Urine Activates the Epithelial Sodium Channel. J Am Soc Nephrol. 2008;20(2):299-310. doi: 10.1681/asn.2008040364
  36. Collet JP, Mishal Z, Lesty C, et al. Abnormal fibrin clot architecture in nephrotic patients is related to hypofibrinolysis: Influence of plasma biochemical modifications. A possible mechanism for the high thrombotic tendency? Thromb Haemost. 1999;82(5):1482-9.
  37. Rabelink T, Zwaginga J, Koomans H, Sixma J. Thrombosis and hemostasis in renal disease. Kidney Int. 1994;46(2):287-96. doi: 10.1038/ki.1994.274
  38. Chen G, Liu H, Liu F. A glimpse of the glomerular milieu: From endothelial cell to thrombotic disease in nephrotic syndrome. Microvasc Res. 2013;89:1-6. doi: 10.1016/j.mvr.2013.06.011
  39. Gao C, Xie R, Yu C, et al. Procoagulant activity of erythrocytes and platelets through phosphatidylserine exposure and microparticles release in patients with nephrotic syndrome. Thromb Haemost. 2012;107(4):681-9. doi: 10.1160/th11-09-0673
  40. Huang M, Wei R, Wang Z, et al. Mechanisms of hypercoagulability in nephrotic syndrome associated with membranous nephropathy as assessed by thromboelastography. Thromb Res. 2015;136(3):663-8. doi: 10.1016/j.thromres.2015.06.031
  41. Alsharidah A, Bayoumy N, Alzogaibi M, et al. Thrombin generation and endothelial dysfunctional markers in different stages of nephrotic syndrome. J Appl Hematol. 2016;7(4):117. doi: 10.4103/1658-5127.198509
  42. Meyer T, Schulze F, Gröne HJ, Kreuzer H. Simultaneous manifestation of acute myocardial infarction and nephrotic syndrome. Clin Cardiol. 1998;21(7):519-22. doi: 10.1002/clc.4960210713
  43. 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. doi: 10.2215/CJN.04250511
  44. Brater DC, Ellison DH. Mechanism of action of diuretics – UpToDate. https://www.uptodate.com/contents/mechanism-of-action-of-diuretics
  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):1111-8. doi: 10.1016/j.kint.2015.12.041
  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):91-9. doi: 10.24920/11809; http://cmsj.cams.cn/EN/10.24920/11809
  47. Roy C, Deschaintre Y, Sabbagh R, et al. Ischemic Stroke of Possible Embolic Etiology Associated With Nephrotic Syndrome. Kidney Int Rep. 2017;2(5):988-94. doi: 10.1016/j.ekir.2017.04.004
  48. Benjamin EJ, Virani SS, Callaway CW, et al. Heart disease and stroke statistics – 2018 update: A report from the American Heart Association. Circulation. 2018;137(12):E67-E492. doi: 10.1161/CIR.0000000000000558
  49. Huang J, Lin C, Chang Y, et al. Nephrotic Syndrome is Associated with Increased Risk of Ischemic Stroke. J Stroke Cerebrovasc Dis. 2019;28(11):104322. doi: 10.1016/j.jstrokecerebrovasdis.2019.104322
  50. McGill HC, McMahan CA, Zieske AW, et al. Association of coronary heart disease risk factors with microscopic qualities of coronary atherosclerosis in youth. Circulation. 2000;102(4):374-9. doi: 10.1161/01.CIR.102.4.374
  51. Berlyne GM, Mallick NP. Ischaemic heart-disease as a complication of nephrotic syndrome. Lancet. 1969;2(7617):399-400. doi: 10.1016/s0140-6736(69)90110-x
  52. Ordoñez J, Hiatt R, Killebrew E, Fireman B. The increased risk of coronary heart disease associated with nephrotic syndrome. Kidney Int. 1993;44(3):638-42. doi: 10.1038/ki.1993.292
  53. Osula S, Bell GM, Hornung RS. Acute myocardial infarction in young adults: Causes and management. Postgrad Med J. 2002;78(915):27-30. doi: 10.1136/pmj.78.915.27
  54. Khatri VP, Fisher JB, Granson MA. Spontaneous arterial thrombosis associated with nephrotic syndrome: Case report and review of the literature. Nephron. 1995;71(1):95-7. doi: 10.1159/000188680
  55. Xie L, Tang Y, Liu J, et al. Acute myocardial infarction in patients of nephrotic syndrome: a case series. J Geriatr Cardiol. 2017;14(7):481-4. doi: 10.11909/j.issn.1671-5411.2017.07.009
  56. 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):190-5. doi: 10.1038/ki.2011.312
  57. Kumar S, Chapagain A, Nitsch D, Yaqoob MM. Proteinuria and hypoalbuminemia are risk factors for thromboembolic events in patients with idiopathic membranous nephropathy: An observational study. BMC Nephrol. 2012;13(1). doi: 10.1186/1471-2369-13-107
  58. Kayali F, Najjar R, Aswad F, et al. Venous Thromboembolism in Patients Hospitalized with Nephrotic Syndrome. Am J Med. 2008;121(3):226-30. doi: 10.1016/j.amjmed.2007.08.042
  59. 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. doi: 10.1148/radiol.14140121
  60. Li SJ, Guo JZ, Zuo K, et al. Thromboembolic complications in membranous nephropathy patients with nephrotic syndrome-a prospective study. Thromb Res. 2012;130(3):501-5. doi: 10.1016/j.thromres.2012.04.015
  61. Благова О.В., Дземешкевич С.Л., Козловская Н.Л. и др. Успешное лечение массивного тромбоза нижней полой вены с нефротическим синдромом и хронической двусторонней тромбоэмболией легочной артерии у пациента с генетической тромбофилией. Терапевтический архив. 2012;84(1):41-7 [Blagova OV, Dzemeshkevich SL, Kozlovskaia NL, et al. Successful treatment of massive thrombosis of the vena cava inferior with nephrotic syndrome and chronic bilateral pulmonary artery thromboembolism in a patient with genetic thrombophilia. Therapeutic Archive. 2012;84(1):41-7 (In Russ.)]. https://www.ncbi.nlm.nih.gov/pubmed/22616531
  62. Appenzeller S, Zeller CB, Annichino-Bizzachi JM, et al. Cerebral venous thrombosis: Influence of risk factors and imaging findings on prognosis. Clin Neurol Neurosurg. 2005;107(5):371-8. doi: 10.1016/j.clineuro.2004.10.004
  63. Kakafika AI, Liberopoulos EN, Mikhailidis DP. Fibrinogen: a predictor of vascular disease. Curr Pharm Des. 2007;13(16):1647-59. doi: 10.2174/138161207780831310
  64. Glassock RJ. Prophylactic anticoagulation in nephrotic syndrome: A clinical conundrum. J Am Soc Nephrol. 2007;18(8):2221-5. doi: 10.1681/ASN.2006111300
  65. Hârza 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):555-60. http://www.ncbi.nlm.nih.gov/pubmed/24068403
  66. Heit JA, Michael O’Fallon W, Petterson TM, et al. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: A population-based study. Arch Intern Med. 2002;162(11):1245-8. doi: 10.1001/archinte.162.11.1245
  67. Wolak T, Rogachev B, Tovbin D, et al. Renal vein thrombosis as a presenting symptom of multiple genetic pro-coagulant defects. Nephrol Dial Transplant. 2005;20(4):827-9. doi: 10.1093/ndt/gfh655
  68. Wysokinski WE, Gosk-Bierska I, Greene EL, et al. Clinical Characteristics and Long-term Follow-up of Patients With Renal Vein Thrombosis. Am J Kidney Dis. 2008;51(2):224-32. doi: 10.1053/j.ajkd.2007.10.030
  69. Wei LQ, Rong ZK, Gui L, Shan R Du. CT diagnosis of renal vein thrombosis in nephrotic syndrome. J Comput Assist Tomogr. 1991;15(3):454-7. doi: 10.1097/00004728-199105000-00020
  70. Llach F. Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome. Kidney Int. 1985;28(3):429-39. doi: 10.1038/ki.1985.149
  71. Radhakrishnan J. Venous thromboembolism and membranous nephropathy: So what’s new? Clin J Am Soc Nephrol. 2012;7(1):3-4. doi: 10.2215/CJN.11791111
  72. Cherng SC, Huang WS, Wang YF, et al. The role of lung scintigraphy in the diagnosis of nephrotic syndrome with pulmonary embolism. Clin Nucl Med. 2000;25(3):167-72. doi: 10.1097/00003072-200003000-00001
  73. Бокерия Л.А., Затевахин И.И., Кириенко А.И. и др. Российские клинические рекомендации по диагностике, лечению и профилактике венозных тромбоэмболических осложнений (ВТЭО). Флебология. 2015;9(4-2):2-52 [Bokerija LA, Zatevahin II, Kirienko AI, et al. Rossijskie klinicheskie rekomendacii po diagnostike, lecheniju i profilaktike venoznyh trombojembolicheskih oslozhnenij (VTJeO). Associacija flebologov Rossii, Associacija serdechno-sosudistyh hirurgov Rossii, Vserossijskoe obshhestvo hirurgov, Rossijskoe nauchnoe obshhestvo terapevtov, Obshhestvo specialistov po neotlozhnoj kardiologii. Flebologija. 2015;9(4-2):2-52 (In Russ.)]. https://elibrary.ru/item.asp?id=27718431
  74. Kelddal S, Nykjær K, Gregersen J, Birn H. Prophylactic anticoagulation in nephrotic syndrome prevents thromboembolic complications. BMC Nephrol. 2019;20(1). doi: 10.1186/s12882-019-1336-8
  75. Radhakrishnan J. Hypercoagulability in nephrotic syndrome – UpToDate. https://www.uptodate.com/contents/hypercoagulability-in-nephrotic-syndrome
  76. 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 [Smirnov AV, Dobronravov VA, Sipovskij VG, et al. Clinical practice guidelines for diagnosis, treatment and prognosis of the minimal change disease in adults. Nephrology (Saint-Petersburg). 2014;18(4):68-92 (In Russ.)].
  77. Lee T, Biddle AK, Lionaki S, et al. Personalized prophylactic anticoagulation decision analysis in patients with membranous nephropathy. Kidney Int. 2014;85(6):1412-20. doi: 10.1038/ki.2013.476
  78. Lai S, Barbano B, Cianci R, et al. Rischio emorragico nell’utilizzo di eparina a basso peso molecolare nel paziente nefropatico? [The risk of bleeding associated with low molecular weight heparin in patients with renal failure (Article in Italian)]. G Ital Nefrol. 2010;27(6):649-54.
  79. Hofstra JM, Wetzels JFM. Should aspirin be used for primary prevention of thrombotic events in patients with membranous nephropathy? Kidney Int. 2016;89(5):981-3. doi: 10.1016/j.kint.2016.01.019
  80. Akoglu H, Agbaht K, Piskinpasa S, et al. High frequency of aspirin resistance in patients with nephrotic syndrome. Nephrol Dial Transplant. 2012;27(4):1460-6. doi: 10.1093/ndt/gfr476
  81. Tholl U, Anlauf M, Helmchen U. Clopidogrel and membranous nephropathy. Lancet. 1999;354(9188):1443-4. doi: 10.1016/S0140-6736(99)02586-6

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