Trial reportNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2025
High-flux hemodialysis with polymethylmethacrylate membranes reduces soluble CD40L, a mediator of cardiovascular disease in uremia.
Trial report in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Systolic pressure overload caused pulmonary oxidative stress, vessel remodeling and severe microvascular thrombosis in CD40 knockout mice through promoting platelet aggregation.Redox biology · 2026Article
- Membrane-to-Patient Optimization: Individualized Dialyzer Selection for Extracorporeal Dialysis.Toxins · 2026Review
- The Non-Traditional Cardiovascular Culprits in Chronic Kidney Disease: Mineral Imbalance and Uremic Toxin Accumulation.International journal of molecular sciences · 2025Review
Corrections and comments
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Authors and funding
24 authors.
Funding
Abstract
background and hypothesisMajor adverse cardiovascular events (MACE) are the main cause of mortality in hemodialysis (HD). Soluble CD40 ligand (sCD40L) binds to CD40 on endothelial cells (EC) and vascular smooth muscle cells (VSMC), playing a potential role in MACE. HD registries show a reduced mortality for MACE using the polymethylmethacrylate (PMMA) membrane. Study objectives were (i) to confirm the role of sCD40L as independent predictor and mediator of MACE and (ii) to evaluate the effect of PMMA on sCD40L-mediated vascular aging.
methodsIn 201 patients treated by high-flux HD, sCD40L levels were measured and correlated with MACE; 54/201 patients with sCD40L greater than or equal to the median value were randomized for 9 months in two crossover groups alternatively treated with PMMA or polysulfone (PS): sCD40L and dialytic parameters were recorded. In vitro, the role of sCD40L was studied on EC dysfunction and VSMC calcification after incubation with patients' sera: cells engineered to knock down CD40 by siRNA were also used to confirm the role of CD40-CD40L pathway activation.
resultsAt study admission, the sCD40L median level of 8.4 ng/mL (interquartile range 2.9-12.7) showed the best statistical performance to identify MACE, which occurred in 51/201 (25.4%) patients. Indoxyl sulfate and p-cresyl sulfate directly correlated with sCD40L levels and induced its release by platelets. In comparison with PS, PMMA treatment significantly reduced sCD40L levels, in accordance with its enhanced mass removal by adsorption. In vitro, sera collected after PMMA treatment reduced EC dysfunction and VSMC osteoblastic differentiation through a mechanism involving the CD40-CD40L pathway.
conclusionsCD40L is an independent predictor and mediator of MACE in chronic HD patients. PMMA membrane stably reduced sCD40L under the high-risk cut-off of 8.4 ng/mL. In vitro studies confirmed the role of PMMA in the reduction of EC dysfunction and VSMC calcification in association with sCD40L modulation.
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