Combining Diffusion, Convection and Absorption: A Pilot Study of Polymethylmethacrylate versus Polysulfone Membranes in the Removal of P-Cresyl Sulfate by Postdilution On-Line Hemodiafiltration

Molina, Pablo; Peiró, Julio; Martínez-Gómez, María Amparo; Vizcaíno, Belén; Esteller, Cristina; González-Moya, Mercedes; García-Valdelvira, María; Vila, María Dolores Molina; Maduell, Francisco

doi:10.3390/kidneydial1020015

Cited by 10 publications

(5 citation statements)

References 59 publications

(84 reference statements)

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“…PMMA membrane is a synthetic polymer membrane with a homogeneous symmetric structure and larger pores on the inner surface. A few studies suggested removing a wide range of proteins by adsorption in addition to diffusion and filtration with hemodialysis using PMMA membranes [12,14]. Our results showed that the removal of β 2 -m by PMMA membranes was mainly due to adsorption (Fig.…”

Section: Discussionmentioning

confidence: 61%

Removal of α1-Microglobulin Using Post-Dilution Online Hemodiafiltration with Polymethylmethacrylate Membrane: An Open-Label, Single-Arm Study

Yoshida,

Yamamoto,

Miyauchi

et al. 2023

Blood Purif

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Introduction: The removal of low- and medium-molecular-weight proteins has been improved with online hemodiafiltration (OL-HDF) and hemodialysis using high-flux membranes; however, the outcomes of patients with end-stage kidney disease (ESKD) undergoing dialysis treatment are still worse than in the general population. α1-Microglobulin (α1-m), with a molecular weight of 33,000 Da, may contribute to dialysis-related disorders and mortality. However, the removal is insufficient even with current OL-HDF using the polysulfone (PS) membrane, which is common in Japan. Polymethylmethacrylate (PMMA) membranes can remove medium- to high-molecular-weight proteins by adsorption. This study aimed to assess the efficacy of removing medium- to high-molecular-weight proteins, such as α1-m and β2-microglobulin (β2-m), through post-dilution OL-HDF with PMMA (Post-PMMA). The assessment was conducted in comparison to pre-dilution OL-HDF with PS (Pre-PS), using an open-label, single-arm study. Methods: Seven patients with ESKD on Pre-PS underwent Post-PMMA with replacement volume of 30 mL/min (low flow) and 50 mL/min (high flow). Clearance and removal rates of α1-m, β2-m, small molecules, inflammatory cytokines, and albumin were measured at 60 and 240 min of treatment. Results: Clearance rates of α1-m at 60 min were −2.8 ± 5.2 mL/min with Pre-PS, −0.4 ± 2.6 mL/min with Post-PMMA (low), and 0.6 ± 3.4 mL/min with Post-PMMA (high). The removal rate of α1-m was higher in Post-PMMA than that in Pre-HDF-PS (Post-PMMA [high] 17.7 ± 5.9%, Post-PMMA [low] 15.0 ± 5.6%, and Pre-PS 4.1 ± 5.5%). Adsorption clearance of β2-m was increased with Post-PMMA. Albumin leakage in Post-PMMA was not higher than that in Pre-PS. Conclusion: The removal rate of α1-m with Post-PMMA was higher than that with Pre-PS. The PMMA membrane adsorbed β2-m, suggesting the removal effect of medium- to high-molecular-weight proteins by the adsorption method. Since Post-PMMA effectively removes α1-m without excessive albumin leakage, it will be useful for patients with ESKD, especially those with a poor nutritional status.

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Section: Discussionmentioning

confidence: 61%

Removal of α1-Microglobulin Using Post-Dilution Online Hemodiafiltration with Polymethylmethacrylate Membrane: An Open-Label, Single-Arm Study

Yoshida,

Yamamoto,

Miyauchi

et al. 2023

Blood Purif

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“…The latter has enhanced adsorptive properties. The reduction ratio for p-cresyl sulfate was higher with the polymethylmethacrylate membrane [70].…”

Section: Adsorptionmentioning

confidence: 83%

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

et al. 2023

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A hallmark of chronic kidney disease is the retention of solutes that normally are eliminated by the kidneys. The current classification defines uremic toxins based on molecular weight and protein affinity. The retention of solutes is already detected in the early stages of the disease when patients are pauci-symptomatic or asymptomatic but the role of therapies to retard the loss of kidney function in patients with chronic kidney disease (e.g., modulators of the renin-angiotensin-aldosterone system, sodium-glucose cotransporter inhibitors) in reducing uremic toxins is poorly understood. Most of the research evaluating the impact of therapies to lower serum concentrations of those toxic compounds is carried out in patients with kidney failure already undergoing kidney replacement therapy. The removal of those molecules relies in physicochemical mass transfer phenomena, i.e., adsorption, diffusion, and convection. In the past 2 decades, the rise and broad adoption of blood purification strategies with enhanced convective properties, such as high-volume online hemodiafiltration and expanded hemodialysis, considerably amplified the ability to mechanically extract middle molecules (molecular weight >0.5 kDa) from the blood compartment. Nonetheless, the classification of uremic toxins has not evolved in parallel with dialysis advancements. Mounting evidence demonstrates the link between middle molecules with uremic symptoms, cardiovascular and mortality risks. An urgent need for updating the classification exists. Defining the causative relationship between specific solutes and specific clinical outcomes will promote the development of targeted therapies. In parallel, the inclusion of new pertinent dimensions to the classification like the influence of new dialysis membranes, sorbents, and intestinal chelators in the concentration of uremic toxins would improve the understanding of the pathogenesis of chronic kidney disease, setting the pace for future research in nephrology.

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“…In the last years, novel PMMA membranes have been improved and adapted for a new renal replacement modality such as online HDF. The new PMMA membranes (e.g., BG-U) appear to be highly effective in reducing p-cresyl sulfate levels when compared to PS membranes [ 70 ]. All these data suggest that the indication of PMMA dialyzers may represent a practical compromise in efficient dialysis treatment.…”

Section: Pmma Can Ameliorate Immunological Impairment During Hdmentioning

confidence: 99%

Enhancing Immune Protection in Hemodialysis Patients: Role of the Polymethyl Methacrylate Membrane

et al. 2023

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End-stage renal disease (ESRD) is characterized by deep disorders in both innate and adaptive immune systems that imply unbalance deactivation and immunosuppression. The central, widely recognized factors responsible for this immune dysregulation are uremia, uremic toxin retention, hemodialysis membrane biocompatibility, and related cardiovascular complications. Recently, several studies strengthened the concept that dialysis membranes are not considered as a simple diffusive/adsorptive device but as a platform to personalize a dialysis approach to improve the quality of life of ESRD patients. Therefore, understanding of the molecules associated with altered immune response is crucial and could lead to therapeutically intervention or adaptation of the dialysis procedure itself for the management of immunological dysfunction of ESRD patients. The polymethyl methacrylate (PMMA)-based membrane is characterized by a symmetrical structure with large-sized pores, providing a better hydrophobic and cationic adsorption capacity compared to the other synthetic membranes. Together with hydrophobic interactions, the high adsorption rate of cytokines (i.e., IL-6) can also be enhanced by the size of nano-pores placed on the membrane surface. PMMA membranes exhibit adsorptive properties for a large amount of uremic toxins including p-cresol and indoxyl sulfate, as well as β2-microglobulin characterized by higher molecular weight, maintaining the diffusive clearance of small molecules like urea with a great biocompatibility. Besides exerting a strong anti-inflammatory effects in line with the improvement of immune responses in patients undergoing dialysis, PMMA also plays a role in modulating adaptive immune response, i.e., can clear blood from soluble CD40, a natural antagonist of the CD40/CD40L signaling that acts inhibiting immunoglobulin production by B cells. This review provides an overview of the main concepts and current understanding of immune dysfunction in hemodialysis and summarizes the recent findings regarding PMMA-based dialysis as potential strategy to restore immune balance in ESRD patients.

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Combining Diffusion, Convection and Absorption: A Pilot Study of Polymethylmethacrylate versus Polysulfone Membranes in the Removal of P-Cresyl Sulfate by Postdilution On-Line Hemodiafiltration

Cited by 10 publications

References 59 publications

Removal of α<sub>1</sub>-Microglobulin Using Post-Dilution Online Hemodiafiltration with Polymethylmethacrylate Membrane: An Open-Label, Single-Arm Study

Removal of α<sub>1</sub>-Microglobulin Using Post-Dilution Online Hemodiafiltration with Polymethylmethacrylate Membrane: An Open-Label, Single-Arm Study

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

Enhancing Immune Protection in Hemodialysis Patients: Role of the Polymethyl Methacrylate Membrane

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