Expanded Haemodialysis Therapy of Chronic Haemodialysis Patients Prevents Calcification and Apoptosis of Vascular Smooth Muscle Cells in vitro

Abstract

Background: Vascular calcification is a common phenomenon in patients with chronic kidney disease and strongly associated with increased cardiovascular mortality. Vascular calcification is an active process mediated in part by inflammatory processes in vascular smooth muscle cells (VSMC). These could be modified by the insufficient removal of proinflammatory cytokines through conventional high-flux (HF) membranes. Recent trials demonstrated a reduction of inflammation in VSMC by use of dialysis membranes with a higher and steeper cut-off. These membranes caused significant albumin loss. Therefore, the effect of high retention Onset (HRO) dialysis membranes on vascular calcification and its implications in vitro was evaluated. Methods: In the PERCI II trial, 48 chronic dialysis patients were dialyzed using HF and HRO dialyzers and serum samples were collected. Calcifying VSMC were incubated with the serum samples. Calcification was determined using alizarin red staining (AZR) and determination of alkaline phosphatase (ALP) activity. Furthermore, apoptosis was evaluated, and release of matrix Gla protein (MGP), osteopontin (OPN) and growth differentiation factor 15 (GDF-15) were measured in cell supernatants. Results: Vascular calcification in vitro was significantly reduced by 24% (ALP) and 36% (AZR) after 4 weeks of HRO dialysis and by 33% (ALP) and 48% (AZR) after 12 weeks of dialysis using HRO membranes compared to HF dialysis. Apoptosis was significantly lower in the HRO group. The concentrations of MGP and OPN were significantly elevated after incubation with HF serum compared to HRO serum and healthy controls. Similarly, GDF-15 release in the supernatant was elevated after incubation with HF serum, an effect significantly ameliorated after treatment with HRO medium. Conclusions: Expanded haemodialysis therapy reduces the pro-calcific potential of serum from dialysis patients in vitro. With a markedly reduced albumin filtration compared to high cut-off dialysis, use of the HRO dialyzers may possibly provide a treatment option for chronic dialysis patients to reduce the progression of vascular calcification.

Is Expanded Hemodialysis an Option to Online Hemodiafiltration for Small- and Middle-Sized Molecules Clearance?

“…The next question to answer will be: is this clearance of medium molecules achieved with HDx associated with better patient outcomes? The answer seems to be yes, as suggested by a recently study published by Willy et al [23]. This study shows that HDx reduces the vascular calcifications in chronic HD patients.…”

Vitamin K Dependent Proteins in Kidney Disease

“…There are no comparative studies on glomerular filtration with respect to the size of the four molecules of VKDPs. However, two studies tested filtration through dialysis membranes, but only MGP was assessed among the four VKDPs [29,30]. Both studies observed that, after incubation with conventional HF serum, VSMCs produced significantly higher concentrations of MGP than VSMCs under HCO, MCO and HRO serums.…”

“…The process of identification, selection, screening and inclusion of the studies are depicted in Figure 1. The following studies were included: MGP [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42]; OC [9,10,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69]; Gas6 [70,71,72,73,74,75,76,77,78,79,80,8...…”

“…A possible explanation of this decline in pro-calcifying activity could be that, after incubation with serum from HF, VSMCs produced considerably higher anti-calcifying proteins (e.g., MGP) than VSMCs incubated in HCO or Medium Cut-Off dialysis (MCO) serums, as a compensatory response to the augmented calcification environment. In addition, according to Willy et al [29], High Retention Onset dialyzers (HRO) may offer a treatment option to diminish the progression of VC, but they come with significant albumin loss. As an alternative, the HRO with a steeper cut-off in their dialysis membrane are faintly less permeable, sustaining the desired effect on in vitro calcification, meanwhile limiting the albumin loss.…”

High-volume online haemodiafiltration treatment and outcome of end-stage renal disease patients: more than one mode

“…Limited studies have demonstrated potential clinical benefits of MCO membranes in reducing cardiovascular risk by reduction of vascular calcification [29] and by decreasing the inflammatory allostatic load associated with retention of middle molecular weight uremic toxins [30]. With the potential of better removal of larger middle molecules, HDX may improve pruritus and restless legs syndrome [31].…”