We observed in our patients when they underwent HFR as compared to HD. Interestingly, similar values of percent decrease in plasma p-cresol concentration after HD were recently reported by Meert et al.. Therefore, our data suggest that HFR could perform better than HD in p-cresol removal though this conclusion remains to be confirmed in larger studies specifically designed to address this point. Finally, regarding classical hemodiafiltration, a previous work showed that total p-cresol concentration decreases by 40% after post-dilution and 42% after pre-dilution HDF but no comparative study with HFR has ever been performed. Although the HFR cartridge retained IL-6, we did not observe any significant change in serum concentrations of this cytokine when we compared blood samples collected before and following a single HFR session. This finding could be explained considering that the actual amount of IL-6 removed during a single HFR is presumably small. Based on concentration in UF and on the value of Quf in the HFR system, we estimated that less than 10% of circulating IL-6 could be removed by the cartridge. Remarkably, no additional IL-6 removal can occur in the diffusive stage of the HFR apparatus because free IL-6 cannot be dialyzed by the low flux membrane of its filter. It is likely that the small amount of IL-6 removed by HFR could be entirely replaced either by the new synthesis of this cytokine or by its release from tissues. It has been suggested, indeed, that in inflamed patients, circulating IL-6 remains high despite its very short plasma half-life because it is produced at a very high rate. Under this respect we should consider that all our patients showed a remarkable systemic inflammation as demonstrated by the high serum concentrations of hsCRP. It should be emphasized at this point, however, that such a marked systemic inflammation is not the most typical finding in ESRD patients that, instead, usually present only a moderate inflammatory state known as ‘‘microinflammation’’. We can speculate, thus, that HFR that was ineffective against the high IL-6 concentration of our markedly inflamed patients could perform better in the average ESRD patient with microinflammation. Our findings suggest that HFR does not differ from other dialysis systems that have all been shown ineffective in lowering the circulating levels of IL-6 and/or of other cytokines. Specifically, IL-6 levels did not change after a single HD session, as shown by Tarakc¸iog˘lu et al. and as also observed by us in the present paper. In addition, continuous hemofiltration was also ineffective in lowering circulating IL-6 levels in patients with systemic inflammatory response syndrome. After measuring the very small amounts of several cytokines such as TNFa and IL1 that are removed by low-volume HF, Van Bommel et al. estimated that a UF volumes of at least 50 L/day should be needed to clear the plasma from these molecules using hemofiltration.