Flow Dynamic Analysis by Contrast-Enhanced Imaging Techniques of Medium Cutoff Membrane Hemodialyzer

Abstract

<b><i>Introduction:</i></b> Medium cutoff (MCO) membranes represent an interesting innovation in the field of hemodialysis. Given the correlation between large (PM >25 kDa) middle molecules (LMM) and clinical outcomes, the possibility to broaden the spectrum of solutes removed in hemodialysis with MCO membranes introduces a new perspective for end-stage kidney disease patients. Due to low diffusion coefficients of LMM, the use of convection is required to maximize extracorporeal clearance. High convective rates are achieved with high-flux membranes in hemodiafiltration, a technique not available in the US. In case of the MCO membrane, remarkable clearances of LMM are achieved combining the permeability of the membrane with a significant amount of internal convection. The mechanism of filtration-backfiltration inside the dialyzer enables effective removal of LMM in a technique called expanded hemodialysis (HDx). Given such theoretical explanation, it is important to demonstrate the blood and ultrafiltration rheology inside the MCO dialyzer. <b><i>Method:</i></b> This study for the first time describes flow dynamic parameters and internal cross-filtration, thanks to specific radiology and nuclear imaging techniques. <b><i>Results:</i></b> Flow dynamic analysis of the blood and dialysate compartment confirms excellent distribution of velocities and an excellent matching of blood and dialysate. Average blood flow velocity allows for wall shear rates adequate to avoid protein stagnation at the blood membrane interface and increase in blood viscosity. Cross-filtration analysis demonstrates a remarkable filtration/backfiltration flux reaching values >30 mL/min at a blood flow of 300 mL/min and zero net filtration. <b><i>Conclusion:</i></b> The MCO dialyzer Theranova 400 appears to have a design optimized to perform expanded hemodialysis (HDx).

Rationale for a New Classification of Solutes of Interest in Chronic Kidney Disease and Hemodialysis

“…2), the removal of middle molecules was not enhanced. The details on how the MCO membrane boosts the removal of middle molecules involve the mechanisms of backfiltration/internal filtration, are beyond the scope of this review, and have been dissected elsewhere [43][44][45][46][47][48][49][50][51][52].…”

Effects of Expanded Hemodialysis with Medium Cut-Off Membranes on Maintenance Hemodialysis Patients: A Review

“…During the manufacturing process, MCO membranes require the hollow fiber diameter to be reduced from the standard 200 μm to 180 μm [ 30 ], which increases the wall shear rate and blood flow velocity [ 40 ], to avoid protein stagnation at the blood membrane interface and improve solute transport [ 41 ]. MCO membranes are thus characterized by higher permeability than classic high-flux membranes due to a remarkable amount of internal filtration (IF) in the proximal part [ 42 ], resulting from an increased end-to-end pressure drop.…”

“…Exogenous substitution fluid and complex set up are not required because there is an adequate amount of backfiltration (BF) [ 43 ] in the distal part of the hemodialyzer, almost covering the convective volumes [ 44 , 45 ]. Lorenzin [ 43 ] recorded dynamic imaging after injecting a non-diffusible marker molecule (albumin macro-aggregates labeled with 99 Tc metastable) and successfully demonstrated the existence of an IF-BF mechanism even though it was not visible [ 41 ]. In vitro, the amount of filtration and backfiltration inside the Theranova 400 dialyzer was found to be more than 30 mL/min at the blood flow of 300 mL/min and at zero net filtration.…”

“…It could reach values around 50 mL/min when there were higher blood flow, larger surface area, and higher net filtration rates (15–20 mL/min). Internal filtration between 30 and 50 mL/min combined with the sieving characteristics of MCO membranes allows for convective clearance values of medium-large molecules equal or even superior to those achieved in high-volume online HDF, without the need for fluid replacement and very high filtration fractions inside the hemodialyzer [ 30 , 36 , 41 ].…”

Advances in Enhancing Hemocompatibility of Hemodialysis Hollow-Fiber Membranes

“…Most recently, advances in the membrane manufacturing have led to the development of a novel class of dialysis membranes with a molecular weight cut-off close to the molecular weight of albumin called medium cut-off (MCO) membrane (Theranova hemodialyzer) [ 31 ]. The MCO membrane has medium apertures, uniform distribution of pores, a steep sieve curve close to the native kidney, and unique internal filtration–backfiltration mechanism [ 32 ]. Growing clinical evidence collectively suggests that expanded hemodialysis with the MCO membrane shows greater capacity to remove middle-molecular weight toxins than conventional high-flux dialysis, and the MCO membrane may alleviate the status of micro-inflammation and oxidative stress, and may partly improve quality of life in patients receiving chronic hemodialysis [ 33 – 35 ].…”