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