Pulmonary embolism in a young patient with nephrotic syndrome: a case report.

Pulmonary embolism in a young patient with nephrotic syndrome: a case report. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Pulmonary embolism in a young patient with nephrotic syndrome: a case report. A Dulcetti, C Bruscia, D M. Malena, G Murante, A Angelino, M Rocchietti March, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4545792/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Feb, 2025 Read the published version in SN Comprehensive Clinical Medicine → Version 1 posted 4 You are reading this latest preprint version Abstract Introduction Nephrotic syndrome (NS) is characterized by the presence of proteinuria of ≥ 3 g/24 h, hypoalbuminemia < 2.5 g/dl, peripheral edema, and severe hyperlipidaemia. NS is associated with increased risk of deep venous thrombosis (DVT), and, consequently, pulmonary embolism (PE) . Case presentation We report a case of a severe PE in a young patient with NS, admitted to the Emergency Medicine Department of the University Hospital Sant’Andrea of Rome. Conclusions The aim of this report is to allow a more comprehensive knowledge of the SN and its related EP highlighting both the risk of underdiagnosis and the need of a multidisciplinary approach by a team of different specialists. We also reviewed pathophysiology of hypercoagulability in NS characterized by the imbalance of prothrombotic and antithrombotic factors, and by impaired thrombolytic activities. A more complete knowledge of the clinical and laboratory features of NS and its related PE appears to be crucial for the early diagnosis and treatment. Pulmonary Embolism Nephrotic Syndrome prothrombotic risk Figures Figure 1 Introduction Pulmonary Embolism (PE) is the third most common cardiovascular disease ( 1 , 2 ). PE is characterized by tachycardia, tachypnea, syncope, chest pain, although it can be asymptomatic and remains undiagnosed until cardiac collapse or sudden death occur ( 3 ). The prevalence of EP among young patients is unknown and could be associated with different predisposing conditions characterized by hypercoagulability ( 1 , 4 , 5 ). NS is characterized by proteinuria of ≥ 3 g/24 hours, reduced level of albuminemia < 2.5 g/dl, peripheral edema and hyperlipidemia, lipiduria, and increased thrombotic risk. Common primary causes of NS are focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), and minimal change disease (MCD) ( 6 ). The estimated annual incidence of NS in healthy children is two to seven new cases per 100,000 children aged < 18 years whereas in adults, the incidence is approximately 3 cases per 100,000 per year ( 8 ). Common causes of NS secondary to systemic diseases are diabetes mellitus, systemic lupus erythematosus, multiple myeloma, amyloidosis, malignancy, and infections. The pathophysiology of hypercoagulability associated with SN is not entirely understood although several factors are believed to play a role ( 5 ). The increased coagulopathy is characterized by an enhanced platelet activity with red blood cell activation mediated by thromboxane A2 and arachidonic acid, increased concentration of fibrinogen, Von Willebrand factor, factor V and VII, and decreased concentrations of protein S, antithrombin III e plasmin. Furthermore, diuretic use in patients with NS may potentiate hemoconcentration thus promoting clot formation. Case presentation Herein, we report a case of a young women aged 35 years with severe PE associated with SN. The patient was admitted to the Emergency Department of the University Hospital Sant’Andrea of Rome since she suffered of 3 syncopal episodes associated with the presence of lower limb edema and dyspnea. Laboratory examinations of blood and urine samples showed proteinuria (spot proteinuria 100 mg/dl) and hypoalbuminemia (2.2 g/dl),. She had no history of drug use including oral contraceptives. However, the patient reported a history of bacterial tonsillitis treated with fluoroquinolones 15 days before the admission to the Hospital. At the clinical examination, she was alert, and oriented, with pale skin (not sweaty). She also exhibited reduced blood pressure (100/60 mmHg), high heart rate (110 bpm), higher respiratory rate (24/min), grade 2 lower limb edema, and normal oxygen saturation (97%). Blood tests showed normal levels of hemoglobin (15.7 g/dl), red blood cells (RBC) (5300000/ul), platelets (PLT) (250000/ul), and white blood cells (WBC) (7610/ul), liver and kidney markers in the normal range. Blood levels of D dimer were high (30670 ng/ml), with nearly normal level of troponin (350 pg/ml). During the stay in the emergency room, the patient underwent angio-computed tomography (CT) that showed the presence of thrombi in both right and left pulmonary arteries, suggestive of massive PE, areas of pulmonary infarctions along with deep venous thrombosis (DVT) with endoluminal thrombotic apposition of the common and left internal iliac vein (Fig. 1 ). Electrocardiogram (ECG) evaluation showed sinus tachycardia, normal intraventricular conduction, and normal ventricular repolarization. Echocardiogram exam showed normal left and right ventricular size and function, and diastolic D shape with a pulmonary artery systolic pressure value of 45 mmHg. The patient as treated with an intravenous heparin bolus of 80 UI/Kg followed by an intravenous infusion of 18 UI/Kg. The nephrologist consultant suggested to treat the patient with corticosteroids on the basis of PE diagnosis in the context of NS. The patient was admitted to the Intensive Care Coronary Unit (ICCU) to monitor vital signs and symptoms, and to continue the therapies. The patient was treated with prednisone 1 mg/kg/die; after 5 days of intravenous heparin infusion, the anti-coagulant therapy was shifted to edoxaban. The following laboratory tests were performed: complement C3 and C4, autoimmune markers including anti-nuclear antibodies (ANA), anti-cardiolipin IgG and IgM, anti-double strand or ds-DNA, extractable nuclear antigen (ENA), Factor II and V polymorphisms, JAK 2 mutation, anti-phospholipase A2 receptor (anti-PLA2R), and anti-thrombin (AT) III which resulted normal. A pharyngotonsillar culture showed absence of pathogenic bacteria growth. Blood levels of low density lipoprotein (LDL) cholesterol were 206 mg/dl, and triglycerides were 218 mg/dl. After 15 days of hospitalization, the lower limb edema was reduced, proteinuria decreased to 500 mg/24h, and blood albumin levels increased to 4.3 g/dl. At patient discharge, the following therapies were recommended: prednisolone, edoxaban, atorvastatin, and ramipril. Close follow-up by nephrologist was also recommended. The successful response to prednisone treatment and the negativity for PLA2R were suggestive for minimal change nephropathy, and, therefore, renal biopsy was not performed. Conclusions PE is a serious complication of deep venous thrombosis (DVT) and represents a potentially lethal disorder ( 1 , 2 ). Although it is well known that the incidence of PE increases with age, PE has been shown to be also an important cause of mortality in younger people. Common risk factors for developing DVT and PE at a young age include recent surgery interventions, prolonged immobilization, autoimmune diseases such as inflammatory bowel disease, and conditions such as NS and antiphospholipid antibodies characterized by hypercoagulability [3,4] . A comprehensive clinical approach that comprises the assessment of all potential thrombotic risk factors is crucial. Nephrotic syndrome is a disorder characterized by increased risk for thrombotic events including deep vein thrombosis, renal vein thrombosis, and pulmonary embolism. The pathophysiological mechanisms responsible for the increase in thrombotic events during nephrotic syndrome are not entirely defined. Increased platelet activation and imbalance between procoagulant and anticoagulant factors are thought to play a role in increasing thrombotic risk in patients with NS. NS is characterized by a damage to the glomerulus, resulting in dysfunction and impaired permeability to various endogenous molecules leading to proteinuria, hypoalbuminemia, and lipiduria ( 5 ). The condition of hypercoagulability observed in patients with primary NS is considered to be secondary to glomerular pathology. Hypoalbuminemia represents an additional independent risk factor for thrombotic risk as supported by the observation that each 1 g/dl reduction in albumin increases the risk of VTE by approximately 2.13 times ( 6 ). The histological diagnosis of NS may represent another risk factor since there is evidence that membranous nephropathy is associated with an increased risk of VTE ( 7 ). Age is also an important risk factor for VTE in patients with NS as suggested by the finding that adult patients are at greater risk of VTE than children ( 8 ). Notably, NS is associated with an increased risk of renal vein thrombosis which may cause pulmonary embolism ( 9 ). There are few studies in the literature regarding the primary prevention of thromboembolism associated with NS, which mainly recommend to evaluate various risk factors for DVT, and TEP with special emphasis on the role of the serum albumin level. A global approach including assessments of a large spectrum of thrombotic risk factors is essential in the management of patients with NS at increased risk of thrombotic events. Declarations Fundings: None. Conflicts of interest: The authors declare that they have no conflict of interest. Consent to partecipate/for publication: Written informed consent was obtained by patient for publication of this case. Data availability: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Code availability: NA Authors' contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by A.D, A.A, B.M., B.A. The first draft of the manuscript was written by A.D, C.B, D. M, M.R.M and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.” Ethics approval: NA References Toplis E, Mortimore G. The diagnosis and management of pulmonary embolism. Br J Nurs. 2020;29(1):22–26. 10.12968/bjon.2020.29.1.22 . PMID: 31917939. Pulido T, Aranda A, Zevallos MA, Bautista E, Martínez-Guerra ML, Santos LE, Sandoval J. Pulmonary embolism as a cause of death in patients with heart disease: an autopsy study. Chest. 2006;129(5):1282-7. 10.1378/chest.129.5.1282 . PMID: 16685020. Heit JA, O'Fallon WM, Petterson TM, Lohse CM, Silverstein MD, Mohr DN, Melton LJ 3rd. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study. Arch Intern Med. 2002;162(11):1245-8. 10.1001/archinte.162.11.1245 . PMID: 12038942. Zöller B, Li X, Sundquist J, Sundquist K. Risk of pulmonary embolism in patients with autoimmune disorders: a nationwide follow-up study from Sweden. Lancet. 2012;379(9812):244–9. 10.1016/S0140-6736(11)61306-8 . Epub 2011 Nov 25. PMID: 22119579. Hull RP, Goldsmith DJ. Nephrotic syndrome in adults. BMJ. 2008;336(7654):1185–9. 10.1136/bmj.39576.709711.80 . PMID: 18497417; PMCID: PMC2394708. Lionaki S, Derebail VK, Hogan SL, Barbour S, Lee T, Hladunewich M, Greenwald A, Hu Y, Jennette CE, Jennette JC, Falk RJ, Cattran DC, Nachman PH, Reich HN. Venous thromboembolism in patients with membranous nephropathy. Clin J Am Soc Nephrol. 2012;7(1):43–51. Epub 2011 Nov 10. PMID: 22076873; PMCID: PMC3265338. Barbour SJ, Greenwald A, Djurdjev O, Levin A, Hladunewich MA, Nachman PH, Hogan SL, Cattran DC, Reich HN. Disease-specific risk of venous thromboembolic events is increased in idiopathic glomerulonephritis. Kidney Int. 2012;81(2):190–5. 10.1038/ki.2011.312 . Epub 2011 Sep 14. PMID: 21918501. Allison EDDY, SYMONS A, Jordan M. Nephrotic syndrome in childhood. lancet. 2003;362(9384):629–39. Kayali F, Najjar R, Aswad F, Matta F, Stein PD. Venous thromboembolism in patients hospitalized with nephrotic syndrome. Am J Med. 2008;121(3):226 – 30. 10.1016/j.amjmed.2007.08.042 . PMID: 18328307. Cite Share Download PDF Status: Published Journal Publication published 15 Feb, 2025 Read the published version in SN Comprehensive Clinical Medicine → Version 1 posted Reviewers agreed at journal 09 Sep, 2024 Reviewers invited by journal 03 Aug, 2024 Editor assigned by journal 30 Jul, 2024 First submitted to journal 29 Jul, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4545792","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":335518737,"identity":"d30bb695-8627-40c2-a0f7-603307d7b5b0","order_by":0,"name":"A Dulcetti","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABE0lEQVRIiWNgGAWjYNACAwbGBnYwS0KOn70BJGKBRzkzVAuIPpAgYSzZcwAkIkFACwNcC0PihhsJYOtwauCf3X/wcUGBjeyGw8wPH3/8YZHYcPP51Q0/CiQY+Nu7E7BpkbhzmNl4hkGa8YbDbMYGIIc1zs4pu9kDdJjEmbMbsFpzI5lNmsfgcOKGwzxsEkAtss3SOWk3eIBaDCRysWqRR9LC/gOohbFN8kzazT94tBgg2wIKMcUeCfZjt/HZYngj2diYB+iXmUC/SJxJkzCW4Mlhuy1jIMGDyy9yNxIfPub5YyPbd7z54YcKmzo5++PHn91888dGjr+9F7v3sQAeAzBJrHIQYH9AiupRMApGwSgY/gAAEENiuD8spvcAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-5912-7722","institution":"Universita di Roma Sapienza Facolta di Psicologia 2: Universita degli Studi di Roma La Sapienza Facolta di Medicina e Psicologia","correspondingAuthor":true,"prefix":"","firstName":"A","middleName":"","lastName":"Dulcetti","suffix":""},{"id":335518738,"identity":"32aa78e9-20f0-4eba-b1bd-c9f157eab671","order_by":1,"name":"C Bruscia","email":"","orcid":"","institution":"Sapienza University of Rome: Universita degli Studi di Roma La Sapienza","correspondingAuthor":false,"prefix":"","firstName":"C","middleName":"","lastName":"Bruscia","suffix":""},{"id":335518739,"identity":"95d61b15-f2c1-4061-b368-72f72ecfd364","order_by":2,"name":"D M. Malena","email":"","orcid":"","institution":"Sapienza Università di Roma: Universita degli Studi di Roma La Sapienza","correspondingAuthor":false,"prefix":"","firstName":"D","middleName":"M.","lastName":"Malena","suffix":""},{"id":335518740,"identity":"f9b0fa16-b338-4a32-aa9e-bee0c6667c84","order_by":3,"name":"G Murante","email":"","orcid":"","institution":"Sant'Andrea Hospital: Azienda Ospedaliera Sant'Andrea","correspondingAuthor":false,"prefix":"","firstName":"G","middleName":"","lastName":"Murante","suffix":""},{"id":335518741,"identity":"d917a995-0c23-456e-9389-516100673d4c","order_by":4,"name":"A Angelino","email":"","orcid":"","institution":"Azienda Ospedaliera Sant'Andrea","correspondingAuthor":false,"prefix":"","firstName":"A","middleName":"","lastName":"Angelino","suffix":""},{"id":335518742,"identity":"89d3b4ee-618a-4498-a5bc-0e517b7319c4","order_by":5,"name":"M Rocchietti March","email":"","orcid":"","institution":"Sapienza Università di Roma: Universita degli Studi di Roma La Sapienza","correspondingAuthor":false,"prefix":"","firstName":"M","middleName":"Rocchietti","lastName":"March","suffix":""},{"id":335518743,"identity":"39103bc1-ff20-40a6-a26d-fd02f121ebbf","order_by":6,"name":"B Mariani","email":"","orcid":"","institution":"Sapienza Università di Roma: Universita degli Studi di Roma La Sapienza","correspondingAuthor":false,"prefix":"","firstName":"B","middleName":"","lastName":"Mariani","suffix":""},{"id":335518744,"identity":"e756c8da-3641-435e-b6ec-da04e08076fa","order_by":7,"name":"B Alfei","email":"","orcid":"","institution":"Azienda Ospedaliera Sant'Andrea","correspondingAuthor":false,"prefix":"","firstName":"B","middleName":"","lastName":"Alfei","suffix":""},{"id":335518745,"identity":"d9b70ac2-3eac-4e1e-b3a9-640b31a35f8c","order_by":8,"name":"A Martocchia","email":"","orcid":"","institution":"Sapienza Università di Roma: Universita degli Studi di Roma La Sapienza","correspondingAuthor":false,"prefix":"","firstName":"A","middleName":"","lastName":"Martocchia","suffix":""},{"id":335518746,"identity":"779c2a80-fdd6-4369-b978-703b02e8bbe2","order_by":9,"name":"G Sesti","email":"","orcid":"","institution":"Sapienza Università di Roma: Universita degli Studi di Roma La Sapienza","correspondingAuthor":false,"prefix":"","firstName":"G","middleName":"","lastName":"Sesti","suffix":""}],"badges":[],"createdAt":"2024-06-07 11:22:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4545792/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4545792/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s42399-025-01780-z","type":"published","date":"2025-02-15T15:57:06+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":64164332,"identity":"b2da428d-2c13-465d-b3e1-19777e7e32bf","added_by":"auto","created_at":"2024-09-09 08:48:39","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":383417,"visible":true,"origin":"","legend":"\u003cp\u003eCT Pulmonary Embolism.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4545792/v1/2b0bfda7332e06e715c9a3a1.jpeg"},{"id":76487448,"identity":"8eb12597-84e0-4501-b8c2-3e1715b99b6b","added_by":"auto","created_at":"2025-02-17 16:06:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":642136,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4545792/v1/90bdb80d-3a93-4597-9080-ed7bf101b1d4.pdf"}],"financialInterests":"","formattedTitle":"Pulmonary embolism in a young patient with nephrotic syndrome: a case report.","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePulmonary Embolism (PE) is the third most common cardiovascular disease (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). PE is characterized by tachycardia, tachypnea, syncope, chest pain, although it can be asymptomatic and remains undiagnosed until cardiac collapse or sudden death occur (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe prevalence of EP among young patients is unknown and could be associated with different predisposing conditions characterized by hypercoagulability (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eNS is characterized by proteinuria of \u0026ge;\u0026thinsp;3 g/24 hours, reduced level of albuminemia\u0026thinsp;\u0026lt;\u0026thinsp;2.5 g/dl, peripheral edema and hyperlipidemia, lipiduria, and increased thrombotic risk. Common primary causes of NS are focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), and minimal change disease (MCD) (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). The estimated annual incidence of NS in healthy children is two to seven new cases per 100,000 children aged\u0026thinsp;\u0026lt;\u0026thinsp;18 years whereas in adults, the incidence is approximately 3 cases per 100,000 per year (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Common causes of NS secondary to systemic diseases are diabetes mellitus, systemic lupus erythematosus, multiple myeloma, amyloidosis, malignancy, and infections.\u003c/p\u003e \u003cp\u003eThe pathophysiology of hypercoagulability associated with SN is not entirely understood although several factors are believed to play a role (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The increased coagulopathy is characterized by an enhanced platelet activity with red blood cell activation mediated by thromboxane A2 and arachidonic acid, increased concentration of fibrinogen, Von Willebrand factor, factor V and VII, and decreased concentrations of protein S, antithrombin III e plasmin. Furthermore, diuretic use in patients with NS may potentiate hemoconcentration thus promoting clot formation.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eHerein, we report a case of a young women aged 35 years with severe PE associated with SN. The patient was admitted to the Emergency Department of the University Hospital Sant\u0026rsquo;Andrea of Rome since she suffered of 3 syncopal episodes associated with the presence of lower limb edema and dyspnea. Laboratory examinations of blood and urine samples showed proteinuria (spot proteinuria 100 mg/dl) and hypoalbuminemia (2.2 g/dl),. She had no history of drug use including oral contraceptives. However, the patient reported a history of bacterial tonsillitis treated with fluoroquinolones 15 days before the admission to the Hospital. At the clinical examination, she was alert, and oriented, with pale skin (not sweaty). She also exhibited reduced blood pressure (100/60 mmHg), high heart rate (110 bpm), higher respiratory rate (24/min), grade 2 lower limb edema, and normal oxygen saturation (97%).\u003c/p\u003e \u003cp\u003eBlood tests showed normal levels of hemoglobin (15.7 g/dl), red blood cells (RBC) (5300000/ul), platelets (PLT) (250000/ul), and white blood cells (WBC) (7610/ul), liver and kidney markers in the normal range. Blood levels of D dimer were high (30670 ng/ml), with nearly normal level of troponin (350 pg/ml). During the stay in the emergency room, the patient underwent angio-computed tomography (CT) that showed the presence of thrombi in both right and left pulmonary arteries, suggestive of massive PE, areas of pulmonary infarctions along with deep venous thrombosis (DVT) with endoluminal thrombotic apposition of the common and left internal iliac vein (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Electrocardiogram (ECG) evaluation showed sinus tachycardia, normal intraventricular conduction, and normal ventricular repolarization. Echocardiogram exam showed normal left and right ventricular size and function, and diastolic D shape with a pulmonary artery systolic pressure value of 45 mmHg. The patient as treated with an intravenous heparin bolus of 80 UI/Kg followed by an intravenous infusion of 18 UI/Kg. The nephrologist consultant suggested to treat the patient with corticosteroids on the basis of PE diagnosis in the context of NS. The patient was admitted to the Intensive Care Coronary Unit (ICCU) to monitor vital signs and symptoms, and to continue the therapies. The patient was treated with prednisone 1 mg/kg/die; after 5 days of intravenous heparin infusion, the anti-coagulant therapy was shifted to edoxaban. The following laboratory tests were performed: complement C3 and C4, autoimmune markers including anti-nuclear antibodies (ANA), anti-cardiolipin IgG and IgM, anti-double strand or ds-DNA, extractable nuclear antigen (ENA), Factor II and V polymorphisms, JAK 2 mutation, anti-phospholipase A2 receptor (anti-PLA2R), and anti-thrombin (AT) III which resulted normal. A pharyngotonsillar culture showed absence of pathogenic bacteria growth. Blood levels of low density lipoprotein (LDL) cholesterol were 206 mg/dl, and triglycerides were 218 mg/dl. After 15 days of hospitalization, the lower limb edema was reduced, proteinuria decreased to 500 mg/24h, and blood albumin levels increased to 4.3 g/dl. At patient discharge, the following therapies were recommended: prednisolone, edoxaban, atorvastatin, and ramipril. Close follow-up by nephrologist was also recommended. The successful response to prednisone treatment and the negativity for PLA2R were suggestive for minimal change nephropathy, and, therefore, renal biopsy was not performed.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003ePE is a serious complication of deep venous thrombosis (DVT) and represents a potentially lethal disorder (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Although it is well known that the incidence of PE increases with age, PE has been shown to be also an important cause of mortality in younger people. Common risk factors for developing DVT and PE at a young age include recent surgery interventions, prolonged immobilization, autoimmune diseases such as inflammatory bowel disease, and conditions such as NS and antiphospholipid antibodies characterized by hypercoagulability [3,4] .\u003c/p\u003e \u003cp\u003eA comprehensive clinical approach that comprises the assessment of all potential thrombotic risk factors is crucial. Nephrotic syndrome is a disorder characterized by increased risk for thrombotic events including deep vein thrombosis, renal vein thrombosis, and pulmonary embolism.\u003c/p\u003e \u003cp\u003eThe pathophysiological mechanisms responsible for the increase in thrombotic events during nephrotic syndrome are not entirely defined. Increased platelet activation and imbalance between procoagulant and anticoagulant factors are thought to play a role in increasing thrombotic risk in patients with NS.\u003c/p\u003e \u003cp\u003eNS is characterized by a damage to the glomerulus, resulting in dysfunction and impaired permeability to various endogenous molecules leading to proteinuria, hypoalbuminemia, and lipiduria (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The condition of hypercoagulability observed in patients with primary NS is considered to be secondary to glomerular pathology. Hypoalbuminemia represents an additional independent risk factor for thrombotic risk as supported by the observation that each 1 g/dl reduction in albumin increases the risk of VTE by approximately 2.13 times (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe histological diagnosis of NS may represent another risk factor since there is evidence that membranous nephropathy is associated with an increased risk of VTE (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Age is also an important risk factor for VTE in patients with NS as suggested by the finding that adult patients are at greater risk of VTE than children (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Notably, NS is associated with an increased risk of renal vein thrombosis which may cause pulmonary embolism (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). There are few studies in the literature regarding the primary prevention of thromboembolism associated with NS, which mainly recommend to evaluate various risk factors for DVT, and TEP with special emphasis on the role of the serum albumin level. A global approach including assessments of a large spectrum of thrombotic risk factors is essential in the management of patients with NS at increased risk of thrombotic events.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFundings:\u0026nbsp;None.\u003c/p\u003e\n\u003cp\u003eConflicts of interest: The authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003eConsent to partecipate/for publication: Written informed consent was obtained by patient for publication of this case.\u003c/p\u003e\n\u003cp\u003eData availability: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eCode availability: NA\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by A.D, A.A, B.M., B.A.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The first draft of the manuscript was written by A.D, C.B, D. M, M.R.M and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u0026rdquo;\u003c/p\u003e\n\u003cp\u003eEthics approval: NA\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eToplis E, Mortimore G. The diagnosis and management of pulmonary embolism. Br J Nurs. 2020;29(1):22\u0026ndash;26. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.12968/bjon.2020.29.1.22\u003c/span\u003e\u003cspan address=\"10.12968/bjon.2020.29.1.22\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 31917939.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePulido T, Aranda A, Zevallos MA, Bautista E, Mart\u0026iacute;nez-Guerra ML, Santos LE, Sandoval J. Pulmonary embolism as a cause of death in patients with heart disease: an autopsy study. Chest. 2006;129(5):1282-7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1378/chest.129.5.1282\u003c/span\u003e\u003cspan address=\"10.1378/chest.129.5.1282\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 16685020.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeit JA, O'Fallon WM, Petterson TM, Lohse CM, Silverstein MD, Mohr DN, Melton LJ 3rd. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study. Arch Intern Med. 2002;162(11):1245-8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/archinte.162.11.1245\u003c/span\u003e\u003cspan address=\"10.1001/archinte.162.11.1245\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 12038942.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZ\u0026ouml;ller B, Li X, Sundquist J, Sundquist K. Risk of pulmonary embolism in patients with autoimmune disorders: a nationwide follow-up study from Sweden. Lancet. 2012;379(9812):244\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0140-6736(11)61306-8\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(11)61306-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2011 Nov 25. PMID: 22119579.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHull RP, Goldsmith DJ. Nephrotic syndrome in adults. BMJ. 2008;336(7654):1185\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bmj.39576.709711.80\u003c/span\u003e\u003cspan address=\"10.1136/bmj.39576.709711.80\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 18497417; PMCID: PMC2394708.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLionaki S, Derebail VK, Hogan SL, Barbour S, Lee T, Hladunewich M, Greenwald A, Hu Y, Jennette CE, Jennette JC, Falk RJ, Cattran DC, Nachman PH, Reich HN. Venous thromboembolism in patients with membranous nephropathy. Clin J Am Soc Nephrol. 2012;7(1):43\u0026ndash;51. Epub 2011 Nov 10. PMID: 22076873; PMCID: PMC3265338.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarbour SJ, Greenwald A, Djurdjev O, Levin A, Hladunewich MA, Nachman PH, Hogan SL, Cattran DC, Reich HN. Disease-specific risk of venous thromboembolic events is increased in idiopathic glomerulonephritis. Kidney Int. 2012;81(2):190\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/ki.2011.312\u003c/span\u003e\u003cspan address=\"10.1038/ki.2011.312\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2011 Sep 14. PMID: 21918501.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAllison EDDY, SYMONS A, Jordan M. Nephrotic syndrome in childhood. lancet. 2003;362(9384):629\u0026ndash;39.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKayali F, Najjar R, Aswad F, Matta F, Stein PD. Venous thromboembolism in patients hospitalized with nephrotic syndrome. Am J Med. 2008;121(3):226\u0026thinsp;\u0026ndash;\u0026thinsp;30. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.amjmed.2007.08.042\u003c/span\u003e\u003cspan address=\"10.1016/j.amjmed.2007.08.042\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 18328307.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Pulmonary Embolism, Nephrotic Syndrome, prothrombotic risk","lastPublishedDoi":"10.21203/rs.3.rs-4545792/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4545792/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIntroduction\u003c/p\u003e\n\u003cp\u003eNephrotic syndrome (NS) is characterized by the presence of proteinuria of ≥ 3 g/24 h, hypoalbuminemia \u0026lt; 2.5 g/dl, peripheral edema, and severe hyperlipidaemia. NS is associated with increased risk of deep venous thrombosis (DVT), and, consequently, pulmonary embolism (PE) .\u003c/p\u003e\n\u003cp\u003eCase presentation\u003c/p\u003e\n\u003cp\u003eWe report a case of a severe PE in a young patient with NS, admitted to the Emergency Medicine Department of the University Hospital Sant’Andrea of Rome.\u003c/p\u003e\n\u003cp\u003eConclusions\u003c/p\u003e\n\u003cp\u003eThe aim of this report is to allow a more comprehensive knowledge of the SN and its related EP highlighting both the risk of underdiagnosis and the need of a multidisciplinary approach by a team of different specialists. We also reviewed pathophysiology of hypercoagulability in NS characterized by the imbalance of prothrombotic and antithrombotic factors, and by impaired thrombolytic activities. A more complete knowledge of the clinical and laboratory features of NS and its related \u0026nbsp;PE appears to be crucial for the early diagnosis and treatment.\u003c/p\u003e","manuscriptTitle":"Pulmonary embolism in a young patient with nephrotic syndrome: a case report.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-09 08:48:31","doi":"10.21203/rs.3.rs-4545792/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2024-09-09T23:59:38+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-03T09:50:38+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-30T08:05:57+00:00","index":"","fulltext":""},{"type":"submitted","content":"SN Comprehensive Clinical Medicine","date":"2024-07-29T09:34:57+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"9614596b-6c6e-4f82-9503-bb115e94dbb3","owner":[],"postedDate":"September 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-02-17T15:59:31+00:00","versionOfRecord":{"articleIdentity":"rs-4545792","link":"https://doi.org/10.1007/s42399-025-01780-z","journal":{"identity":"sn-comprehensive-clinical-medicine","isVorOnly":false,"title":"SN Comprehensive Clinical Medicine"},"publishedOn":"2025-02-15 15:57:06","publishedOnDateReadable":"February 15th, 2025"},"versionCreatedAt":"2024-09-09 08:48:31","video":"","vorDoi":"10.1007/s42399-025-01780-z","vorDoiUrl":"https://doi.org/10.1007/s42399-025-01780-z","workflowStages":[]},"version":"v1","identity":"rs-4545792","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4545792","identity":"rs-4545792","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}