Nephrotic syndrome (NS) is a pathological state of the glomerular filtration barrier associated with an increased venous and arterial thrombotic risk. Current guidelines suggest heparin-based or vitamin K antagonist (VKA) regimens for thromboprophylaxis in such patients. Although widely prescribed for other indications, direct oral anticoagulants (DOACs) are not recommended in NS because of limited pharmacological and safety reports. This study aimed to compare DOACs and VKAs for thromboprophylaxis in NS, specifically regarding thrombotic events (TEs) and bleeding events (BEs). We conducted a retrospective monocentric analysis of recorded NS episodes that required prophylactic anticoagulation between January 2006 and December 2023. We included 133 NS episodes of which 51 were treated with DOACs and 82 with VKAs. The primary endpoint was a composite endpoint, including thrombosis occurrence and major or clinically significant BEs during thromboprophylaxis. The secondary endpoints consisted of relevant features potentially involved when each primary endpoint was considered independently. Patient characteristics, underlying NS etiology, personal thrombotic and bleeding risk factors, and biological parameters were globally similar in both groups. The primary endpoint appeared similar in both groups (P = 0.481). The secondary endpoints were mostly hypothesis-generating because of the low TE (n = 2) and BE (n = 7) occurrences. This study provides reassuring clinical data on DOAC use in NS thromboprophylaxis compared with VKAs, the recommended therapy, and calls for confirmation in randomized controlled trials (RCTs) and larger pharmacological studies.

Background: Arteriovenous fistula (AVF) is the preferred vascular access option for hemodialysis (HD). The latter requires a remodeling process called maturation that can take up to 3 months. Maturation failure is a frequent complication associated with significant morbidity. The prevalence of antiphospholipid antibody (aPL) positivity in HD patients is high and may result in thrombosis of the vascular access. Recently, aPL persistent positivity has been associated with AVF maturation failure in a retrospective study including 116 patients. Methods: We are conducting an observational prospective cohort study aiming to evaluate this association. Included patients are planned for AVF creation, aged over 18 years old, and have an interpretable aPL assay confirmed at 12 weeks and without any other innate or acquired thrombophilia or inflammatory disease. Primary endpoints will be the evaluation of AVF maturation clinically and by ultrasound. Secondary endpoints will focus on clinical outcomes other than AVF maturation (i.e., primary patency, thrombosis or stenosis, bleeding and hemodialysis adequacy parameters). Conclusions: This prospective observational cohort study aims to examine the possibly causative link between aPL persistent positivity and AVF maturation failure. This study was registered on ClinicalTrials.gov (ID number: NCT06112821).

Pro-inflammatory and pro-thrombotic stimuli can activate endothelial cells (ECs) and predispose them to thrombotic microangiopathies (TMAs). Drug-induced TMA (DITMA) may occur in clinical practice during treatment with interferon-β1a (IFN-β1a), ciclosporin A (CsA), and gemcitabine (GEM). DITMA may also trigger the complement system and induce membrane attack complex (MAC, C5b-9) deposition in vivo , although their role and the benefit of inhibition remain unclear. In an experimental in vitro model of microvascular ECs exposed to these three drugs, we searched for MAC deposits and drug-specific pro-inflammatory and pro-thrombotic traits to gain insights into the mechanisms potentially involved in DITMA. Human microvascular endothelial cells line-1 (HMEC-1) was treated with 10% normal human serum, CsA, GEM, and IFN-β1a. Cell viability for each drug was measured using the resazurin assay. Cell component expression of the following markers involved in endothelial pathogenic activation was measured via immunofluorescence and flow cytometry: C5b-9, interleukin (IL)-1α, IL-6, E-selectin, platelet EC adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), and von Willebrand factor (vWF). Levels of plasminogen activator inhibitor-1 (PAI-1) and urokinase plasminogen activator (uPA) were measured in the supernatants using the enzyme-linked immunosorbent assay (ELISA). Significantly increased C5b-9 deposits were found with each drug, and increased drug-specific activation marker expressions appeared in HMEC-1s when exposed to CsA (IL-1α, IL-6, ICAM-1, E-selectin, vWF, and uPA), GEM (IL-1α, IL-6, PECAM-1, ICAM-1, E-selectin, and vWF), and IFN-β1a (PECAM-1, ICAM-1, PAI-1, and uPA). Each drug induces MAC deposits on HMEC-1s and singular endothelial activation profiles, potentially leading to thrombogenesis observed in DITMA.

Introduction: Endothelial dysfunction is a common feature of end-stage kidney disease, requiring hemodialysis (HD) and antiphospholipid antibody (aPL) persistent positivity. Endothelial dysfunction can be assessed with noninvasive tests such as flow-mediated dilation (FMD). In the HD population, it is not known whether aPL persistent positivity is associated with a more severe endothelial dysfunction. Methods: We performed a cross-sectional study in our HD patients. The FMD of the brachial artery was measured in 17 aPL-positive patients who fulfilled the inclusion criteria and were matched to 17 controls according to age, gender, diabetes mellitus, smoking status and markers of dialysis adequacy (Kt/V). Results: FMD was significantly lower in the aPL group with a mean of 6.9% and 11.8% in the aPL-positive and the control groups, respectively (mean difference (IC 95%): −4.9 (−8.3; −1.6), p = 0.006). aPL was associated with a higher c-reactive protein level, and longer HD vintage. There was no statistical difference between groups in terms of pre-dialysis urea and urinary output, dialysis adequacy (Kt/V), and history of cardiovascular disease or treatments. Conclusions: aPL persistent positivity in HD patients was associated with worse endothelial dysfunction, reflected by FMD measurements. These findings have to be confirmed in larger studies.