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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
PubMed

Insights

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 dysfunction

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