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BMC Nephrology

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Open Access 01-12-2024 | Urokinase | Research

Urokinase prophylactic anticoagulation in children with nephrotic syndrome: a multicenter retrospective cohort study

Authors: Zhen Wang, Nan Wang, Ruyue Chen, Hanyun Tang, Qiang Lin, Xiaozhong Li

Published in: BMC Nephrology | Issue 1/2024

Abstract

Objective

To analyze the clinical effect of urokinase on the prevention of thrombosis in children with primary nephrotic syndrome.

Methods

A total of 370 children diagnosed with primary nephrotic syndrome (PNS) in the Children’s Hospital of Soochow University and Zibo Maternal and Child Health Hospital from January 2018 to December 2022 were selected as the research objects. The patients were divided into a urokinase adjuvant therapy group and non-urokinase adjuvant therapy group according to the application of drugs. The clinical data of the children were collected, including sex, age, drug application, bleeding during treatment, and telephone follow-up, to record whether thromboembolism occurred in the acute stage and remission stage. The clinical pattern of PNS, renal biopsy, histopathological type, and related laboratory indexes before and after treatment were recorded.

Results

A total of 313 patients were treated with urokinase and 57 patients were not. More thrombotic events was observed in non-urokinase group compared to the urokinase group(2 versus 0 episodes, p = 0.02). The thrombotic events observed included one patient had pulmonary embolism combined with right ventricular thrombosis, and another had intracranial venous thrombosis. More minor bleeding events occurred in urokinase group compared to the non-urokinase group(7 versus 1 episodes, p = 1.0). No major bleeding events occurred in either group.

Conclusion

The rational prophylactic use of urokinase anticoagulation in children with PNS can prevent the formation of thromboembolism and has good safety.

Noone DG, Iijima K, Parekh R. Idiopathic nephrotic syndrome in children. Lancet. 2018;392(10141):61–74. https://doi.org/10.1016/S0140-6736(18)30536-1CrossRefPubMed

Gauckler P, Shin JI, Alberici F. Rituximab in adult minimal change disease and focal segmental glomerulosclerosis - what is known and what is still unknown? Autoimmun Rev. 2020;19(11):102671. https://doi.org/10.1016/j.autrev.2020.102671CrossRefPubMed

Watts AJB, Keller KH, Lerner G. Discovery of autoantibodies Targeting Nephrin in Minimal Change Disease supports a novel autoimmune etiology. J Am Soc Nephrol. 2022;33(1):238–52. https://doi.org/10.1681/ASN.2021060794CrossRefPubMedPubMedCentral

Deepyi S, Jasmina A, Akshay K. Thromboembolic complications in childhood nephrotic syndrome: a clinical profile. Clin Exp Nephrol 2014,18(5):803–13. https://doi.org/10.1007/s10157-013-0917-2

Kerlin BA, Ayoob R, Smoyer WE. Epidemiology and pathophysiology of nephrotic syndrome-associated thromboembolic disease. Clin J Am Soc Nephrol. 2012;7:513–20. https://doi.org/10.2215/CJN.10131011CrossRefPubMedPubMedCentral

Wang Z, Tang HY, Lin Q. Incidence of thromboembolism in children with primary nephrotic syndrome: a systematic review and metaanalysis. BMC Nephrol. 2023;24(1):120. Published 2023 May 1. https://doi.org/10.1186/s12882-023-03160-y

Lu CHW, Ying Sh. Clinical analysis of the pulmonary thrombosis in childhood nephrofic syndrome. Beijing Med J. 2011;33(02):163–6. https://doi.org/10.15932/j.0253-9713.2011.02.040CrossRef

Na G, Yong,Huijie X, Xuedong Y, Jie D. Retrospective investigation of 8 children wih nephrotic syndrome complicated with thrombolism. Clin J Evid Based Pediatr 2011,6(04):286–91. https://doi.org/10.3969/j.issn.1673-5501

Sinha I, Klafkowski G, Harrington B, Minchom P, Judd B. Pulmonary embolism in a 3-Year-old boy with nephrotic syndrome. Radiol Case Rep. 2015;2(3):87. https://doi.org/10.2484/rcr.v2i3.87. PMID: 27303477; PMCID: PMC4895064.CrossRefPubMedPubMedCentral

10.

McPheeters RA, Purcell TB, Snyder DL. Fatal pulmonary embolism in a 10-year old with nephrotic syndrome. Cal J Emerg Med. 2003;4(2):36–8.PubMedPubMedCentral

11.

Rodríguez-Fanjul J, Trenchs V, Muñoz-Santanach D. Deep vein thrombosis: rare cases of diagnoses in a pediatric emergency department. Pediatr Emerg Care. 2011;27(5):417–9. https://doi.org/10.1097/PEC.0b013e3182187421CrossRefPubMed

12.

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. https://doi.org/10.1093/jscr/rjaa238CrossRefPubMedPubMedCentral

13.

Heran MKS, Coupal TM, Dionne J. Endovascular pharmacomechanical thrombolysis-a novel treatment for circumaortic left renal vein and inferior vena cava thrombosis in a paediatric patient with relapsing nephrotic syndrome. BJR Case Rep. 2017;4(2):20170082. https://doi.org/10.1259/bjrcr.20170082CrossRefPubMedPubMedCentral

14.

Gonzalez-Gonzalez FJ, Ziccardi MR, McCauley MD. Virchow’s Triad and the role of thrombosis in COVID-Related stroke. Front Physiol. 2021;12:769254. https://doi.org/10.3389/fphys.2021.769254CrossRefPubMedPubMedCentral

15.

Neubauer K, Zieger B. Endothelial cells and coagulation. Cell Tissue Res. 2022;387(3):391–8. https://doi.org/10.1007/s00441-021-03471-2CrossRefPubMed

16.

Zhenhua Y, Xu BYL. Vascular endothelial cell Injury and glomerular diseases. Intern Med China 2012,7(2):163–5. https://doi.org/10.3969/j.issn.1673-7768.2012.02.034

17.

Winter WE, Flax SD, Harris NS. Coagulation testing in the Core Laboratory. Lab Med. 2017;48(4):295–313. https://doi.org/10.1093/labmed/lmx050CrossRefPubMed

18.

Kerlin BA, Blatt NB, Fuh B. 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, 110.e1. https://doi.org/10.1016/j.jpeds.2009.01.070CrossRefPubMedPubMedCentral

19.

Kerlin BA, Haworth K, Smoyer WE. Venous thromboembolism in pediatric nephrotic syndrome. Pediatr Nephrol. 2014;29(6):989–97. https://doi.org/10.1007/s00467-013-2525-5CrossRefPubMed

20.

Tavil B, Kara F, Topaloglu R. Case series of thromboembolic complications in childhood nephrotic syndrome: Hacettepe experience. Clin Exp Nephrol. 2015;19(3):506–13. https://doi.org/10.1007/s10157-014-1005-yCrossRefPubMed

21.

Mahajerin A, Branchford BR, Amankwah EK. Hospital-associated venous thromboembolism in pediatrics: a systematic review and meta-analysis of risk factors and risk-assessment models. Haematologica. 2015;100(8):1045–50. https://doi.org/10.3324/haematol.2015.123455CrossRefPubMedPubMedCentral

22.

Yang B, Kai SH. Pathophysiological mechanism and clinical diagnosis and treatment of thrombosis in nephrotic syndrome. Lab Med Clin. 2014;11(16):2308–10. https://doi.org/10.3969/j.issn.1672-9455.2014.16.053CrossRef

23.

Carpenter SL, Goldman J, Sherman AK. Association of infections and venous thromboembolism in hospitalized children with nephrotic syndrome. Pediatr Nephrol. 2019;34(2):261–7. https://doi.org/10.1007/s00467-018-4072-6CrossRefPubMed

24.

Chuang Z, Xiangqing S. Rational use of anticoagulants in nephrotic syndrome. Pharm Clin Res 2016,24(01):75–8.https://doi.org/10.13664/j.cnki.pcr.2016.01.020

25.

Fahal IH, McClelland P, Hay CR. Arterial thrombosis in the nephrotic syndrome. Postgrad Med J. 1994;70(830):905–9. https://doi.org/10.1136/pgmj.70.830.905CrossRefPubMedPubMedCentral

26.

Lin R, McDonald G, Jolly T. A systematic review of prophylactic anticoagulation in nephrotic syndrome. Kidney Int Rep. 2019;5(4):435–47. https://doi.org/10.1016/j.ekir.2019.12.001

27.

Jiong ZH. Zhihong. Pathophysiology of thromboembolism in nephrotic syndrome.J Nephro Dialy Transplant,2010,19(05):455–9. https://doi.org/10.3969/j.issn.1006-298X.2010.05.013

28.

Tkaczyk M, Baj Z. Surface markers of platelet function in idiopathic nephrotic syndrome in children. Pediatr Nephrol. 2002;17(8):673–7. https://doi.org/10.1007/s00467-002-0865-7CrossRefPubMed

29.

Schlegel N. Thromboembolic risks and complications in nephrotic children. Semin Thromb Hemost. 1997;23(3):271–80. https://doi.org/10.1055/s-2007-996100CrossRefPubMed

30.

Xin-Hua W, Hai-Juan H, Lin-Mei ZH. Clinical analysis of twelve cases with cerebral venous sinus thrombosis in children.Chin J Neurol.2013;46(6):383–386.https://doi.org/10.3760/cma.j.issn.1006-7876.2013.06.007

31.

Guenther RA, Kemp WL. Delayed death due to Saddle Pulmonary Thromboembolus in Child with Nephrotic Syndrome Induced by Focal Segmental Glomerulosclerosis. Am J Forensic Med Pathol. 2018;39(4):370–4. https://doi.org/10.1097/PAF.0000000000000432CrossRefPubMed

32.

Wright JM, Watts RG. Venous thromboembolism in pediatric patients: epidemiologic data from a pediatric tertiary care center in Alabama. J Pediatr Hematol Oncol. 2011;33(4):261–4. https://doi.org/10.1097/MPH.0b013e3182134111CrossRefPubMed

33.

Torres RA, Torres BR, de Castilho AS. Venous sinus thrombosis in a child with nephrotic syndrome: a case report and literature review. Rev Bras Ter Intensiva. 2014;26(4):430–4. https://doi.org/10.5935/0103-507X.20140066CrossRefPubMedPubMedCentral

34.

Boussetta A, Jaber C, Jellouli M, Gargah T. Thromboembolic complications in children with primary nephrotic syndrome: A Tunisian series. Tunis Med. 2022 Janvier;100(1):33–36.

35.

Han KH, Park JY, Min SK. Bilateral iliac and popliteal arterial thrombosis in a child with focal segmental glomerulosclerosis. Korean J Pediatr. 2016;59(5):242–5. https://doi.org/10.3345/kjp.2016.59.5.242CrossRefPubMedPubMedCentral

36.

Kelddal S, Nykjær KM, Gregersen JW. Prophylactic anticoagulation in nephrotic syndrome prevents thromboembolic complications. BMC Nephrol. 2019;20(1):139. https://doi.org/10.1186/s12882-019-1336-8CrossRefPubMedPubMedCentral

37.

Medjeral-Thomas N, Ziaj S, Condon M. Retrospective analysis of a novel regimen for the prevention of venous thromboembolism in nephrotic syndrome. Clin J Am Soc Nephrol. 2014;9(3):478–83. https://doi.org/10.2215/CJN.07190713. Epub 2013 Dec 12.CrossRefPubMed

38.

Van Meerhaeghe T, Cez A, Dahan K. Apixaban Prophylactic Anticoagulation in patients with nephrotic syndrome. TH Open. 2022;6(4):e299–e303. https://doi.org/10.1055/a-1920-6224CrossRefPubMedPubMedCentral

39.

Smith HW, Marshall CJ. Regulation of cell signalling by uPAR. Nat Rev Mol Cell Biol. 2010;11(1):23–36. https://doi.org/10.1038/nrm2821CrossRefPubMed

40.

Montuori N, Ragno P. Role of uPA/uPAR in the modulation of angiogenesis. Chem Immunol Allergy. 2014;99:105–22. https://doi.org/10.1159/000353310CrossRefPubMed

41.

Montuori N, Ragno P. Multiple activities of a multifaceted receptor: roles of cleaved and soluble uPAR. Front Biosci (Landmark Ed). 2009;14(7):2494–503. https://doi.org/10.2741/3392CrossRefPubMed

42.

Gondi CS, Kandhukuri N, Dinh DH. Down-regulation of uPAR and uPA activates caspase-mediated apoptosis and inhibits the PI3K/AKT pathway. Int J Oncol. 2007;31(1):19–27.PubMed

43.

Prager GW, Mihaly J, Brunner PM. Urokinase mediates endothelial cell survival via induction of the X-linked inhibitor of apoptosis protein. Blood. 2009;113(6):1383–90. https://doi.org/10.1182/blood-2008-06-164210CrossRefPubMed

44.

Shutang ZH. Guangqin L.Effect of urokinase on the expression of MMP-9 in human vascular endothelial cells and its mechanism. J Chongqing Med Univ. 2009;2(03):269–72.

45.

Kerlin BA, Blatt NB, Fuh B. Epidemiology and risk factors for thromboembolic complications of childhood nephrotic syndrome: a Midwest Pediatric Nephrology Consortium (MWPNC) study[J]. J Pediatr. 2009;155(1):105–10,. 110.e1. https://doi.org/10.1016/j.jpeds.2009.01.070CrossRefPubMedPubMedCentral

46.

Barbour SJ, Greenwald A, Djurdjev O. Disease-specific risk of venous thromboembolic events is increased in idiopathic glomerulonephritis. Kidney Int. 2012;81(2):190–5. https://doi.org/10.1038/ki.2011.312CrossRefPubMed

47.

Park BS, Park S, Jin K. Nephrotic syndrome complicated with portal, splenic, and superior mesenteric vein thrombosis. Kidney Res Clin Pract. 2014;33(3):161–4. https://doi.org/10.1016/j.krcp.2014.07.001CrossRefPubMedPubMedCentral

48.

Nakajima M, Watari M, Ando Y. Asymptomatic deep venous thrombosis identified on routine screening in patients with hospitalized neurological diseases. J Clin Neurosci. 2022;102:13–20. https://doi.org/10.1016/j.jocn.2022.06.002CrossRefPubMed

49.

Sharathkumar AA, Biss T, Kulkarni K. Epidemiology and outcomes of clinically unsuspected venous thromboembolism in children: a systematic review. J Thromb Haemost. 2020;18(5):1100–12. https://doi.org/10.1111/jth.14739CrossRefPubMedPubMedCentral

50.

Osakwe O, Das B. Successful pulmonary endarterectomy after Acute Pulmonary Embolism and reversal of Acute Cor Pulmonale in an 11-Year-old boy with nephrotic syndrome. Child (Basel). 2022;9(10):1444. https://doi.org/10.3390/children9101444CrossRef

51.

Sakr HI, Edrees B, Taher HO. Combined Methylprednisolone Pulse Therapy plus Rituximab for treating a rare juvenile steroid-resistant nephrotic syndrome with cerebral venous sinus thrombosis: a Case Report. J Cardiovasc Dev Dis. 2022;9(11):383. https://doi.org/10.3390/jcdd9110383CrossRefPubMedPubMedCentral

52.

Yajing H, Xiaolong CH, Huaiqing C. Multiple arterial thrombosis in external iliac artery after thoracoscopic lobectomy in a boy with primary nephrotic syndrome—one case report and literature review. J Clin Ped Sur 2022,21(1):93–6. https://doi.org/10.3760/cma.j.cn.101785-202011020-018

53.

Ningning CH, Tianji G, Min ZH,Meimei Y. Report of a child with nephrotic syndrome and superior sagittal sinus thrombosis. Mod Med J China 2021,23(12):71–3. https://doi.org/10.3969/j.issn.1672-9463.2021.12.020

54.

Lu Y. Yue D,Chengguang ZH.Report of one case of idiopathic membranous nephropathy with renal venous thrombosis as initial symptom. Chin J Practical Pediatr 2021,36(09):703–5. https://doi.org/10.19538/j.ek2021090614

55.

Inaguma Y, Kaito H, Horinouchi T. An old and new complication in a child with nephrotic syndrome: answers. Pediatr Nephrol. 2021;36(7):1955–8. https://doi.org/10.1007/s00467-020-04794-yCrossRefPubMed

56.

Charfeddine S, Yousfi C, Maalej B. Acute myocardial infarction in a child with nephrotic syndrome. Rev Port Cardiol (Engl Ed). 2021;40(6):457e1–4. https://doi.org/10.1016/j.repce.2021.07.011CrossRef

57.

Nagalla VK, Raju SB, Ramesh Bura NR. Arterial thrombosis Associated with factor V Leiden Mutation in a child with nephrotic syndrome: a case report. Indian J Nephrol. 2021 Mar-Apr;31(2):187–9. https://doi.org/10.4103/ijn.IJN_32_18

58.

Jinyu L, Zhongyi Q,Xin W. One case of thromboembolic pulmonary hypertension in plateau area was misdiagnosed: a case report. Stroke Nerv Dis 2020,27(6):835851. https://doi.org/10.3969/j.issn.1007-0478.2020.06.030

59.

Yanhong M, Yinglan L. A case report of thromboembolic pulmonary hypertension in plateau area was misdiagnosed. Chin J Gen Pract 2020,18(6):1063–5. https://doi.org/10.16766/j.cnki.issn.1674-4152.001428

60.

Cuimei L, Liuyi H, Xiaoyun J. Pulmonary embolism in children with nephrotic syndrome: report of two cases and literature review. Chin Pediatr Emerg Med 2020,27(10):779–82. https://doi.org/10.3760/cma.j.issn.1673-4912.2020.10.015

61.

Rathore V, Bhattacharya D, Pandey J. Chylothorax in a child with nephrotic syndrome. Indian J Nephrol. 2020 Jan-Feb;30(1):32–4. https://doi.org/10.4103/ijn.IJN_24_19

62.

He J, Yang F. Cerebral venous sinus thrombosis in a child with idiopathic nephrotic syndrome: a Case Report and Review of the literature. Cureus. 2020;12(10):e11248. https://doi.org/10.7759/cureus.11248CrossRefPubMedPubMedCentral

Title: Urokinase prophylactic anticoagulation in children with nephrotic syndrome: a multicenter retrospective cohort study
Authors: Zhen Wang
Nan Wang
Ruyue Chen
Hanyun Tang
Qiang Lin
Xiaozhong Li
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Urokinase
Nephrotic Syndrome
Thrombosis
Anticoagulant
Low Molecular Weight Heparin
Published in: BMC Nephrology / Issue 1/2024
Electronic ISSN: 1471-2369
DOI: https://doi.org/10.1186/s12882-024-03502-4

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