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막성신증으로 인한 신증후군 환자에서 발생하는 혈전색전증의 위험성 평가와 와파린 선제 항응고 치료법에 대한 개인 맞춤형 의사 결정 분석
Risk Evaluation for Thromboembolism in Subjects with Nephrotic Syndrome Caused by Primary Membranous Nephropathy and Personalized Decision Analysis for Prophylactic Anticoagulation with Warfarin

DC Field Value Language
dc.contributor.advisor유 경 상-
dc.contributor.author이태우-
dc.date.accessioned2017-07-14T01:44:14Z-
dc.date.available2017-07-14T01:44:14Z-
dc.date.issued2016-02-
dc.identifier.other000000132174-
dc.identifier.urihttps://hdl.handle.net/10371/122298-
dc.description학위논문 (박사)-- 서울대학교 대학원 : 의과대학 의과학과 의과학전공, 2016. 2. 유경상.-
dc.description.abstractVascular thromboembolic events have long been recognized as among the most common and serious complications of nephrotic syndrome. Among the underlying diseases of nephrotic syndrome, membranous nephropathy has the highest risk for development of thromboembolism. Making a prudent clinical decision of prophylactic anticoagulation is a challenge for physicians because currently available information on the risks and benefits of the therapy is insufficient. The purposes of this dissertation were: first, to assess the risk of thromboembolic events in venous and arterial vasculatures of patients with primary membranous nephropathy causing nephrotic syndrome-
dc.description.abstractsecond, to evaluate the role of patient characteristics (including demographics, the severity of renal manifestation, and treatments) as risk predictors of clinical thromboembolic events-
dc.description.abstractthird, to categorize patients by risk factors-
dc.description.abstractand, finally, to evaluate the value of a clinical decision to prescribe the prophylactic anticoagulation with warfarin to prevent a thromboembolic event according to the risk categorization. We measured the risks of clinically apparent venous thromboembolic events and arterial thrombosis presenting as cardiovascular events in a large inception cohort consisting of patients with primary membranous nephropathy. Predisposing risk factors of such events were evaluated by survival analysis using a multivariate regression technique. With a systematic review of literature and cohort event analysis, individualized benefits of averting venous thromboembolism and risks of major bleedings from prophylactic anticoagulation with warfarin were obtained. The benefits and risks of the decision to use such a treatment were presented by simulating clinical outcomes in the Markov hybrid decision tree model. The value of the decision was appraised with the risk-benefit ratio of the therapy using a net-benefit framework.
We detected clinically apparent venous thromboembolic events in about 7% of total patient cohorts with primary membranous nephropathy. The degree of hypoalbuminemia of a patient was a significant risk factor for developing thromboembolic events. Cardiovascular events were frequently observed within 2 years after diagnosis of primary membranous nephropathy, when most of the patients presented with severe nephrotic syndrome. The cumulative incidence rate of cardiovascular events was about 5% at 2 years after biopsy, and was as high as commensurate with the incidence of the progression to end stage renal disease. The decision analysis clearly supported the use of prophylactic anticoagulation with warfarin in patients with low risk of major bleeding. The benefit-to-risk ratio was 4.5:1, which means 4.5 major venous thromboembolic events are averted at a cost of one major bleeding in patients at low bleeding risk and serum albumin level <3.0 g/dL. The ratio increased in patients with serum albumin level <2.0 g/dL to 13:1. Patients at intermediate bleeding risk with an albumin under 2 g/dl had a moderately favorable benefit-to-risk ratio (under 5:1). Patients at high bleeding risk were unlikely to benefit from prophylactic anticoagulation regardless of albuminemia. The conducted studies demonstrate how to construct medical evidence on the use of prophylactic anticoagulation in membranous nephropathy with risk evaluation of thromboembolism using individual patient data. This presents an alternative platform of a pragmatic clinical pharmacology pursuing personalized medicine.
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dc.description.tableofcontentsIntroduction 7
Nephrotic syndrome 8
Membranous nephropathy as the most common cause of nephrotic syndrome 8
Thromboembolism as a complication of nephrotic syndrome, membranous nephropathy among the highest risk 9
Risk of venous thromboembolic events (VTE) and associated risk factors in membranous nephropathy 12
Prophylactic anticoagulation to prevent thromboembolism in MN 14
Rationale and Overview of Proposed Research 15

Methods 17
The specific aims and methods to address the objective of the proposal 18
Description of study cohort 20
Methods for Aim1: Examine the risk of CVE (arterial thrombosis) in subjects with primary MN relative to that of progression to ESRD 21
Methods for Aim2: Evaluate the individualized risk of VTE in subjects with primary MN 25
Methods for Aim3: Evaluate the value of the decision for the use of anticoagulation therapy prophylactically to prevent VTE in subjects with primary MN 28

Results 44
Results of Aim1 study: The risk and risk factor of CVE in primary MN 45
Results of Aim2 study: The risk and risk factor of VTE in primary MN 65
Results of Aim3 study: A decision analysis for prophylactic use of anticoagulation 71

Discussion 85
Discussion 1: the risk and risk factor of CVE in primary MN 86
Discussion 2: the risk and risk factor of VTE in primary MN 92
Discussion 3: a decision analysis for prophylactic use of anticoagulation 94

Conclusion 101

Reference 107

Abstract in Korean 118
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dc.formatapplication/pdf-
dc.format.extent1769511 bytes-
dc.format.mediumapplication/pdf-
dc.language.isoen-
dc.publisher서울대학교 대학원-
dc.subjectMembranous Nephropathy-
dc.subjectNephrotic Syndrome-
dc.subjectThromboembolism-
dc.subjectVenous Thromboembolism-
dc.subjectCardiovascular Diseases-
dc.subjectDecision Analysis-
dc.subjectWarfarin-
dc.subject.ddc610-
dc.title막성신증으로 인한 신증후군 환자에서 발생하는 혈전색전증의 위험성 평가와 와파린 선제 항응고 치료법에 대한 개인 맞춤형 의사 결정 분석-
dc.title.alternativeRisk Evaluation for Thromboembolism in Subjects with Nephrotic Syndrome Caused by Primary Membranous Nephropathy and Personalized Decision Analysis for Prophylactic Anticoagulation with Warfarin-
dc.typeThesis-
dc.contributor.AlternativeAuthorTaewoo Lee-
dc.description.degreeDoctor-
dc.citation.pages120-
dc.contributor.affiliation의과대학 의과학과-
dc.date.awarded2016-02-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biomedical Sciences (대학원 의과학과)Theses (Ph.D. / Sc.D._의과학과)
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