{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:10:54Z","timestamp":1791389454001,"version":"4.3.3"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2025,11]]},"abstract":"\n Key Points<\/jats:title>\n \n \n \n Nephrotic syndrome is associated with excessive thrombin generation and impaired fibrinolysis, increasing the risk of thrombosis.<\/jats:p>\n <\/jats:list-item>\n \n Endothelial dysfunction in nephrotic syndrome is markedly by elevated thrombomodulin, syndecan-1, and vWf levels.<\/jats:p>\n <\/jats:list-item>\n \n Findings suggest anticoagulant therapy targeting secondary hemostasis over platelet agents in nephrotic syndrome management.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n Nephrotic syndrome is associated with an increased risk of venous thromboembolism, but the underlying mechanism remains incompletely understood. The efficacy of prophylactic anticoagulant strategies is also poorly documented. To optimize preventive therapy, this study aimed to characterize the coagulation abnormalities in patients with nephrotic syndrome.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This Danish multicenter, cross-sectional study included 47 adult patients with nephrotic syndrome, defined by plasma-albumin <30 g\/L and urine albumin-creatinine ratio >2200 mg\/g. Exclusion criteria included eGFR <30 ml\/min per 1.73 m\n 2<\/jats:sup>\n , ongoing anticoagulant treatment, thrombophilia, prior thrombosis, malignancy, or pregnancy. Markers of endothelial cell function, platelet function, thrombin generation, and fibrinolysis were compared with those of healthy individuals (\n n<\/jats:italic>\n ranging from 10 to 174 depending on assay).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Patients with nephrotic syndrome (\n N<\/jats:italic>\n =47) had significantly increased thrombin generation markers compared with healthy individuals, as indicated by elevated prothrombin fragment 1+2 (509 pmol\/L, 95% confidence interval [CI], 426 to 592 versus 183 pmol\/L; 95% CI, 171 to 196;\n P<\/jats:italic>\n < 0.001) and thrombin-antithrombin complex (3.5\n \u00b5<\/jats:italic>\n g\/L, 95% CI, 3.2 to 3.8 versus 2.5\n \u00b5<\/jats:italic>\n g\/L; 95% CI, 2.3 to 2.7;\n P<\/jats:italic>\n < 0.001). Fibrinolysis was impaired, as demonstrated by prolonged 50% clot lysis time (1281 seconds, 95% CI, 1101 to 1462 versus 964 seconds; 95% CI, 843 to 1085;\n P<\/jats:italic>\n = 0.004). Endothelial cell markers, including thrombomodulin, syndecan-1, and vWf, were significantly elevated. By contrast, platelet function, natural anticoagulants, and other coagulation markers did not differ.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Our results indicate that the prothrombotic state in nephrotic syndrome is driven by excessive thrombin generation and impaired fibrinolysis rather than increased platelet aggregation. In line with current guideline recommendations, this supports the rationale for antithrombotic strategies targeting secondary hemostasis rather than platelet function in patients with nephrotic syndrome.<\/jats:p>\n <\/jats:sec>\n \n Clinical Trial registry name and registration number:<\/jats:title>\n European Union Drug Regulating Authorities Clinical Trials Database (Identifier: 2019-001212-29), ClinicalTrials.gov (Identifier: NCT04850378).<\/jats:p>\n <\/jats:sec>","DOI":"10.34067\/kid.0000000865","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T12:09:50Z","timestamp":1749211790000},"page":"1960-1969","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":5,"title":["Alterations in Coagulation and Endothelial Function in Nephrotic Syndrome"],"prefix":"10.34067","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8873-0814","authenticated-orcid":false,"given":"Sarah","family":"Kelddal","sequence":"first","affiliation":[{"name":"Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark"},{"name":"Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1466-0865","authenticated-orcid":false,"given":"Erik L.","family":"Grove","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2241-5791","authenticated-orcid":false,"given":"Camilla L.","family":"Duus","sequence":"additional","affiliation":[{"name":"University Clinic in Nephrology and Hypertension, G\u00f8dstrup Hospital, Herning, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis B.","family":"Nygaard","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Aalborg University Hospital, Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4009-553X","authenticated-orcid":false,"given":"Tilde","family":"Kristensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark"},{"name":"Medical Diagnostics Center, Viborg Regional Hospital, Viborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5830-5814","authenticated-orcid":false,"given":"Frank H.","family":"Mose","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark"},{"name":"Department of Nephrology, Aalborg University Hospital, Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3306-5165","authenticated-orcid":false,"given":"Jon W.","family":"Gregersen","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Aalborg University Hospital, Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7136-7534","authenticated-orcid":false,"given":"Anne-Mette","family":"Hvas","sequence":"additional","affiliation":[{"name":"Faculty of Health, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3715-7266","authenticated-orcid":false,"given":"Henrik","family":"Birn","sequence":"additional","affiliation":[{"name":"Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark"},{"name":"Department of Biomedicine, Faculty of 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