On-line haemodiafiltration with high volume substitution fluid: long-term efficacy and security.

Sir, On-line haemodiafiltration (HDF) is a technique that combines diffusion with elevated convection in which the substitution fluid is produced directly from the dialysate [1]. The safety of this technique in terms of sterility and nonpirogenicity has been confirmed by several studies [2,3]. The activation of inflammatory systems has been associated with both shortand long-term complications of dialysis, namely: b2-microglobulin amyloidosis, accelerated atherosclerosis, cardiovascular calcifications and mortality, anaemia and malnutrition [4–6]. Several studies suggest that on-line convective therapies provide the most haemocompatible systems, thus reducing the bioreactivity of dialysis [1,2,4]. This is achieved by the use of synthetic, highly permeable membranes, ultra-pure dialysate and the optimization of convection which offers the greatest clearances for lowand high-molecular weight ureamic toxins, and the best biological compatibility thus approaching the function of the normal kidney [4]. The use of HDF in the pre-dilution mode allows higher ultrafiltration rates permitting the highest middle molecule clearances. On the other hand, it has the theoretical disadvantage of reducing blood concentration, thus reducing the clearance of small molecules [7]. In a previous study, we were able to demonstrate that the potentiation, by on-line HDF, of the convective effect of high-flux (HF) polysulphone membrane optimizes their efficacy in terms of solute removal and probable reduction in chronic inflammatory response, as demonstrated by the decrease in the serum levels of inflammatory cytokines such as tumour necrosis factor-a (TNF-a) [5]. With the purpose of evaluating the long-term efficacy and security of on-line HDF with high substitution fluid load (pre-dilution, 250ml/min; 60 l/session), we conducted an historical prospective study, in a group of prevalent and stable chronic haemodialysed patients. Every 3 months, during an year (T0,T3,T6,T9,T12), we measured the removal of small molecules (urea equilibrated Kt/V); middle molecules (serum b2-microglobulin); heavy metals (serum aluminium) and several other biochemical parameters of 28 haemodialysed patients (19 male, mean age 54 13.1 years) submitted to pre-dilution HDF with a reposition volume of 250ml/min. These patients were compared with a control group of 28 HF haemodialysed patients stratified according to time on dialysis, age, gender and presence of diabetes mellitus. The exclusion criteria were: infectious or inflammatory diseases, therapy with non-steroid anti-inflammatory drugs, corticoids or antibiotics. Every patient was dialysed with high-flux polysulphone dialyser and volumetric monitors (HDF 4008-H) both from Fresenius Medical Care. We used ultra-pure water and the endotoxin level was evaluated by the Chromogenic Kinetic Limulus Amoebocyte Lysate (LAL) method. Results were analysed by Student’s t-test. A P< 0.05 was considered statistically significant. As shown in Figure 1 in the group submitted to HDF, serum C-reactive protein levels decreased significantly from the onset of the technique (T0–T3, P1⁄4 0.009); and were maintained during the 12 months of study (P1⁄4 0.04). This profile was not observed in the group submitted to high-flux dialysis. The serum levels of aluminium showed a progressive and significant reduction in both groups (Figure 2). Dialysis adequacy measured by eKt/V was maintained (HDF T01⁄4 1.44 0.21 and T121⁄4 1.42 0.25). Serum b2 microglobulin (HDF T01⁄4 17 283 6518 ng/ml; HDF T121⁄4 16 355 4944 ng/ml) and albumin (HDF T01⁄4 3.96 0.31 g/dl; HDF T121⁄4 4.0 0.37 g/dl) remained stable during the whole study. There were no significant differences in these parameters between pre-dilution HDF and HF dialysis. Our results show, for the first time on a long-term basis, that convection optimization by on-line haemodiafiltration with very high volume substitution fluid (250ml/min), is a safe technique, associated with a reduction in serum inflammatory markers, without compromising dialysis adequacy and the nutritional status of haemodialysed patients.