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PMMA-Based Continuous Hemofiltration Modulated Complement Activation and Renal Dysfunction in LPS-Induced Acute
Alessandra Stasi1, Rossana Franzin1, Chiara Divella1
1Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari "Aldo Moro", Bari, Italy.
Frontiers in Immunology
|April 19, 2021
Summary
Polymethyl methacrylate (PMMA)-based continuous hemofiltration effectively reduced immune system activation and kidney damage in a sepsis model. This treatment limited complement activation and fibrosis, offering a promising approach for sepsis-induced acute kidney injury.
Area of Science:
- Nephrology
- Immunology
- Critical Care Medicine
Background:
- Sepsis-induced acute kidney injury (AKI) is a common and severe complication in critically ill patients.
- Dysregulated innate immune system activation contributes to organ damage and poor prognosis in sepsis.
- Conventional treatments for sepsis-induced AKI are often ineffective.
Purpose of the Study:
- To investigate the efficacy of polymethyl methacrylate (PMMA) membrane-based continuous venovenous hemofiltration (CVVH) in modulating immune activation in a swine model of lipopolysaccharide (LPS)-induced AKI.
- To compare PMMA-CVVH with polysulfone (PS)-CVVH in managing sepsis-induced AKI.
- To assess the impact of PMMA-CVVH on systemic and renal immune markers and gene expression profiles.
Main Methods:
- Establishment of a swine model of LPS-induced AKI.
- Treatment with either PMMA-CVVH or PS-CVVH.
- Evaluation of renal deposition of C5b-9 and Pentraxin-3 (PTX3).
- Assessment of systemic complement activation via ELISA.
- Microarray analysis of gene expression in peripheral blood mononuclear cells (PBMCs), validated by Real-time PCR.
Main Results:
- LPS infusion induced oliguric AKI with tubulo-interstitial inflammation, collagen deposition, and glomerular thrombi.
- Endotoxemic animals showed increased renal PTX-3 and C5b-9 deposits and elevated systemic complement activation.
- PMMA-CVVH significantly reduced both systemic and tissue complement activation, mitigating renal damage and fibrosis.
- Microarray analysis revealed significant differential gene expression in response to LPS and PMMA-CVVH, with key genes involved in immune processes.
Conclusions:
- PMMA-based CVVH demonstrates significant efficacy in modulating immune dysfunction associated with LPS-induced AKI.
- This treatment approach limits complement activation and renal damage, suggesting a potential therapeutic benefit.
- PMMA-CVVH offers a promising strategy for managing sepsis-induced AKI by targeting immunological aberrations.
Keywords:
LPS-induced AKIPMMA-CVVH treatmentcomplement modulationgene expression profileimmunological dysfunctionMore Related Videos
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