Expanded haemodialysis: from operational mechanism to clinical results

Claudio Ronco, Nicola Marchionna, Alessandra Brendolan, Mauro Neri, Anna Lorenzin, Armando J Martínez Rueda, Claudio Ronco, Nicola Marchionna, Alessandra Brendolan, Mauro Neri, Anna Lorenzin, Armando J Martínez Rueda

Abstract

Recent advances in chemical composition and new production techniques resulted in improved biocompatibility and permeability of dialysis membranes. Among these, the creation of a new class of membranes called medium cut-off (MCO) represents an important step towards improvement of clinical outcomes. Such membranes have been developed to improve the clearance of medium to high molecular weight (MW) solutes (i.e. uraemic toxins in the range of 5-50 kDa). MCO membranes have peculiar retention onset and cut-off characteristics. Due to a modified sieving profile, MCO membranes have also been described as high-retention onset. The significant internal filtration achieved in MCO haemodialysers provides a remarkable convective clearance of medium to high MW solutes. The marginal loss of albumin observed in MCO membranes compared with high cut-off membranes is considered acceptable, if not beneficial, producing a certain clearance of protein-bound solutes. The application of MCO membranes in a classic dialysis modality characterizes a new technique called expanded haemodialysis. This therapy does not need specific software or dedicated hardware, making its application possible in every setting where the quality of dialysis fluid meets current standards.

Figures

FIGURE 1
FIGURE 1
Schematic representation of different classes of uraemic toxins with their molecular size and relevant clinical effects.
FIGURE 2
FIGURE 2
Sieving curves of classic HF and MCO membranes. The MWCO and MWRO characterize the shape of the sieving curve for each membrane and ultimately define the permeability properties.
FIGURE 3
FIGURE 3
HDx versus online HDF. The layout of the HDx circuit is simpler and there is no need for reinfusion (Qr) while net UF is set by the fluid balance control of the machine. The mechanism inside the filters is depicted in the lower panels for both techniques. In online HDF, large amounts of UF are achieved with high TMP and then replaced in the venous line after multiple steps of filtration of fresh dialysate. In HDx, the convection flow is maintained by internal filtration but it is compensated by the mechanism of backfiltration inside the filter. The special configuration of the MCO membrane with reduced inner diameter allows for high rates of internal filtration and backfiltration.
FIGURE 4
FIGURE 4
In the left panel, the three theoretical models utilized to estimate internal filtration are reported (reprinted with permission from Lorenzin et al. [32]). The top right panel describes the haematocrit curve and the local filtration in different points along the length of the filter according to the linear theoretical model (reprinted with permission from Lorenzin et al. [32]). In the lower right panel, the scintigraphic images experimentally achieved using a non-diffusible marker molecule in a closed-loop circulation are reported. The curves describe the concentration of the marker molecule along the length of the haemodialysers in a condition of zero net filtration. Variations from inlet to peak concentration allow measurement of direct filtration while the variation from peak concentration to filter outlet allows measurement of backfiltration. These curves were achieved at steady state in conditions of 300 and 400 mL/min of blood flow in a 1.7 MCO haemodialyser. Data confirmed the linear theoretical model prediction.
FIGURE 5
FIGURE 5
Albumin concentrations in six patients treated for 6 months with Theranova filters and HDx.

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Source: PubMed

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