Abstract
Removal of the middle molecules (MM) weight toxins, and particularly of beta-2-microglobuline (b2M) is made first by convection technique with membranes habitually used in hemodiafiltration online (HDFOL). AN69 was in standard hemodialysis (HD) the reference membrane for the removal of b2M mostly (60%) by adsorption. Its use with convective methods is generally restricted to low efficiency modalities with low substitution rates (Qs), either with continuous HF or HDF for acute renal failure, or with acetate free biofiltration (AFB) for chronic renal failure. So-called adsorptive membranes do not have, at the present time, a well-defined indication for high efficiency HDFOL, which necessitates substitution rates (Qs) higher than 15 litres per session. The objective of this study is to demonstrate the feasibility of such an association between polyethyleneimine (PEI) surface treated AN69 and HDFOL both in qualitative and quantitative terms. Five patients were dialysed, respectively, with Nephral 500ST (AN69, PEI, surface 2.15m(2), Hospal France) in HD (HDNEP), postdilution HDF (PostNEP), predilution HDF (PreNEP) and as a reference, with FX80 (Helixone, surface 1,8m(2), Fresenius) in PostD (PostFX). For the small molecules (SM), equilibrated Kt/V (Kt/VEq) and the phosphorus (Ph) reduction ratio (RR)Ph have been measured. Considering the predominating adsorption of b2M by AN69, the removal of MM - b2M and myoglobine (Myo) - was also assessed by their RR (RRb2M and RRMyo). Results are convincing in terms of behaviour in relation to convective techniques, the 2.15m(2) membrane used during 4 hour sessions accepting Qs up to 25 litres with PostD and up to 59 litres with PreD, without any alarm of transmembrane pressure (TMP) or any fiber coagulation incident, proving without any ambiguity the absence of deleterious membrane plugging and its compatibility with high efficiency HDFOL. The behaviour of AN69 in HDFOL in relation to SM does not differ from HDNEP or FXPost. For MM, results for b2M are significantly lower (P=0.01) for PostNEP (RR=71.4%) in comparison with PostFX (RR=79.3%), but the behaviour of AN69 is above all particular for higher molecular weight substances since results are significantly reversed (P=0.03) for Myo (PM=17,800Da) in favour of PostNEP (RR=73.6%) compared to PostFX (RR=65.7%). These results open up new horizons for HDFOL and encourage us to focus future studies on the consequences of an optimized removal, mainly by absorption, of high molecular weight toxins, such as factor D, C3a, C3b and cytokines (IL-1 and TNF). The expected beneficial consequences concern complications linked to inflammation and oxidative stress, which could account notably, beyond the mere quantitative removal of b2M, for the quasi disappearance of any clinical expression of dialysis-related amyloidosis.
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