In Vitro Dialysis of Cytokine-Rich Plasma With High and Medium Cut-Off Membranes Reduces Its Procalcific Activity

Abstract

Recently developed high-flux (HF) dialysis membranes with extended permeability provide better clearance of middle-sized molecules such as interleukins (ILs). Whether this modulation of inflammation influences the procalcific effects of septic plasma on vascular smooth muscle cells (VSMCs) is not known. To assess the effects of high cut-off (HCO) and medium cut-off (MCO) membranes on microinflammation and in vitro vascular calcification we developed a miniature dialysis model. Plasma samples from lipopolysaccharide-spiked blood were dialyzed with HF, HCO, and MCO membranes in an in vitro miniature dialysis model. Afterwards, IL-6 concentrations were determined in dialysate and plasma. Calcifying VSMCs were incubated with dialyzed plasma samples and vascular calcification was assessed. Osteopontin (OPN) and matrix Gla protein (MGP) were measured in VSMC supernatants. IL-6 plasma concentrations were markedly lower with HCO and MCO dialysis. VSMC calcification was significantly lower after incubation with MCO- and HCO-serum compared to HF plasma. MGP and OPN levels in supernatants were significantly lower in the MCO but not in the HCO group compared to HF. In vitro dialysis of cytokine-enriched plasma samples with MCO and HCO membranes reduces IL-6 levels. The induction of vascular calcification by cytokine-enriched plasma is reduced after HCO and MCO dialysis.

Exploring the Clinical Relevance of Providing Increased Removal of Large Middle Molecules

“…Evidence of potential benefit is growing rapidly. In small studies to date, dialysis with MCO membranes has been associated with a reduction in the activation of the renin-angiotensin system (47), reduced serum concentrations and expression of proinflammatory cytokines (TNF-a and IL-6) (48), and reduced induction of vascular calcification (49).…”

The Evolving Patterns of Uremia: Unmet Clinical Needs in Dialysis

“…In prolonged therapy period, the plasma levels of immune-modulatory proteins such as TNF-receptor 1, lambda and kappa free light chain also tend to decrease. In addition, the calcification of vascular smooth muscle cells is significantly lower after incubation with HRO/MCO-and HCO-serum compared to HF plasma in vitro [22] . In contrast, lipoprotein-associated phospholipase A2 were elevated obviously after receiving HDx therapy [19] .…”

Vitamin K Dependent Proteins in Kidney Disease

“…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...…”

“…Willy et al [30] found that serum samples from patients after High Cut-Off dialysis (HCO) have a reduced capacity to induce in vitro calcification in VSMCs compared to patients after conventional High Flow dialysis (HF). 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.…”