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Medium Cut-Off (MCO) Membranes Reduce Inflammation in Chronic Dialysis Patients-A Randomized Controlled Clinical
Daniel Zickler1, Ralf Schindler1, Kevin Willy1
1Charité-Universitaetsmedizin Berlin, Campus Virchow Clinic, Department of Nephrology and Intensive Care Medicine, Berlin, Germany.
Background:
To increase the removal of middle-sized uremic toxins a new membrane with enhanced permeability and selectivity, called Medium Cut-Off membrane (MCO-Ci) has been developed that at the same time ensures the retention of albumin. Because many middle-sized substances may contribute to micro-inflammation we hypothesized that the use of MCO-Ci influences the inflammatory state in hemodialysis patients.
Methods:
The randomized crossover trial in 48 patients compared MCO-Ci dialysis to High-flux dialysis of 4 weeks duration each plus 8 weeks extension phase. Primary endpoint was the gene expression of TNF-α and IL-6 in peripheral blood mononuclear cells (PBMCs), secondary endpoints were plasma levels of specified inflammatory mediators and cytokines.
Results:
After four weeks of MCO-Ci the expression of TNF-α mRNA (Relative quantification (RQ) from 0.92 ± 0.34 to 0.75 ± 0.31, -18.5%, p<0.001)-α and IL-6 mRNA (RQ from 0.78 ± 0.80 to 0.60 ± 0.43, -23.1%, p<0.01) was reduced to a significantly greater extent than with High-flux dialyzers (TNF mRNA-RQ: -14.3%; IL-6 mRNA-RQ: -3.5%). After retransformation of logarithmically transformed data, measurements after MCO were reduced to 82% of those after HF (95% CI 74%-91%). 4 weeks use of MCO-Ci resulted in long-lasting change in plasma levels of several cytokines and other substances with a significant decrease for sTNFR1, kappa and lambda free light chains, urea and an increase for Lp-PLA2 (PLA2G7) compared to High-flux. Albumin levels dropped significantly after 4 weeks of MCO dialysis but increased after additional 8 weeks of MCO dialysis. Twelve weeks treatment with MCO-Ci was well tolerated regarding the number of (S)AEs. In the extension period levels of CRP, TNF-α-mRNA and IL-6 mRNA remained stable in High-flux as well as in MCO-Ci.
Conclusions:
MCO-Ci dialyzers modulate inflammation in chronic HD patients to a greater extent compared to High-flux dialyzers. Transcription of pro-inflammatory cytokines in peripheral leukocytes is markedly reduced and removal of soluble mediators is enhanced with MCO dialysis. Serum albumin concentrations stabilize after an initial drop. These results encourage further trials with longer treatment periods and clinical endpoints.
Insights
Medium Cut-Off (MCO-Ci) dialysis significantly reduces inflammatory markers like TNF-α and IL-6 in hemodialysis patients compared to High-flux. This new membrane enhances toxin removal while stabilizing albumin levels over time.
Area of Science:
- Nephrology
- Biomedical Engineering
- Immunology
Background:
- A novel Medium Cut-Off membrane (MCO-Ci) was developed to enhance middle-sized uremic toxin removal and albumin retention.
- Middle-sized substances are implicated in micro-inflammation, prompting investigation into MCO-Ci's impact on hemodialysis patients' inflammatory status.
Purpose of the Study:
- To evaluate the influence of MCO-Ci dialysis on the inflammatory state in patients undergoing hemodialysis.
- To compare the efficacy of MCO-Ci against High-flux dialysis in modulating inflammatory markers.
Main Methods:
- A randomized crossover trial involving 48 patients compared MCO-Ci dialysis with High-flux dialysis over 4-week periods, followed by an 8-week extension.
- Primary endpoints included gene expression of Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-6 (IL-6) in peripheral blood mononuclear cells (PBMCs).
- Secondary endpoints assessed plasma levels of inflammatory mediators and cytokines.
Main Results:
- MCO-Ci significantly reduced TNF-α mRNA expression by 18.5% and IL-6 mRNA by 23.1% compared to baseline, exceeding reductions seen with High-flux dialysis.
- Plasma levels of soluble TNFR1, kappa and lambda free light chains, and urea decreased with MCO-Ci, while Lp-PLA2 (PLA2G7) increased.
- Serum albumin levels initially dropped but stabilized after 8 weeks of MCO-Ci treatment. Treatment was well-tolerated.
Conclusions:
- MCO-Ci dialyzers demonstrate a greater capacity to modulate inflammation in chronic hemodialysis patients than High-flux dialyzers.
- MCO dialysis markedly reduces pro-inflammatory cytokine transcription in leukocytes and enhances soluble mediator removal.
- Further research with extended treatment durations and clinical endpoints is warranted.
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