Acute kidney injury: effect of hemodialysis membrane on Hgf and recovery of renal function.

OBJECTIVES: Acute kidney injury (AKI) is associated with a high mortality and morbidity rate. In this study we investigated whether dialysis membranes influence the recovery of renal function, through the regulation of hepatocyte growth factor (HGF). DESIGN AND METHODS: 21 patients were enrolled and assigned to hemodialysis (HD) with cellulose (CE, N=11) versus polymethylacrylate (PMMA, N=10) membranes in alternating order. HGF and IL-1 were measured in serum and in peripheral blood mononuclear cells (PBMC) supernatants collected immediately before the first HD session (T0), at 15 minutes (T15), at 240 minutes (T240) and after the last HD, when renal recovery occurred. Eight healthy volunteers were the controls (CON). RESULTS: Time to renal function recovery was lower in CE than in PMMA patients. Serum HGF in HD patients was significantly higher than in CON. HGF levels were higher in CE than in PMMA patients at T15 (13.4±2.7 vs 8.9±3.0 ng/mL, P=0.004) and T240. At recovery, HGF levels decreased. IL-1 serum levels showed a similar trend (at T15 CE: 20.5±2.9 vs PMMA: 16.9±3.2 pg/mL, P=0.005). HGF release significantly increased in the course of HD, resulting in higher levels in CE than that in PMMA patients. Considering all the patients, basal HGF release negatively correlated with time to renal recovery (r2=0.42, P<0.01). CONCLUSIONS: Here we demonstrated that dialysis membranes influence the cytokine profile in AKI patients, HGF release being higher in patients treated with the CE membrane, in comparison to PMMA. Our results suggest that treatment with CE might improve clinical outcomes, possibly through increased release of HGF.

Vitamin E-loaded dialyzer resets PBMC-operated cytokine network in dialysis patients.

BACKGROUND: In hemodialysis patients the activity of stimulated Th1 lymphocytes is depressed, while Th2 cells are constitutively primed. Such phenomena may depend on monocyte activation and altered release of interleukin (IL)-12 and IL-18, which regulate Th cell differentiation. Reactive oxygen species (ROS) activate monocytes; therefore, a hemodialyzer with antioxidant activity would contrast ROS, prevent monocyte activation, reset IL-12 and IL-18 release, and restore Th1/Th2 balance. METHODS: Ten patients on regular dialysis treatment (RDT) with cellulosic membrane (CM) were shifted to vitamin E-coated dialyzer (VE). During treatment with CM and after 3, 6, and 12 months of treatment with VE, peripheral blood mononuclear cells (PBMC) and purified CD4+ cells were isolated, and cultured, resting, mitogen-stimulated, and interferon gamma (IFNgamma), IL-4, IL-10, IL-12, and IL-18 release was measured. Vitamin E and A plasma levels and the effects of a single dialysis session on peripheral blood NO levels were assayed. RESULTS: The constitutive release of IL-4 and IL-10 by CD4+ cells was abated significantly by treatment with VE (nadir -77.8% and -55.3%, respectively, at 12 months). INFgamma release by mitogen-stimulated CD4+ recovered with VE (zenith +501% at 12 months). PBMC constitutive production of IL-12 and IL-18 was significantly reduced by VE (nadir at 12 months -64.7% and -51.3%, respectively). VE increased plasma levels of vitamins E and A. NO plasma levels fell after a single dialysis treatment with VE (-17%, P < 0.05) in contrast with CU (+27.1%, P < 0.05). CONCLUSION: The network of cytokines released by monocytes and Th cells is reset toward normality by treatment with vitamin E-coated dialyzer.