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A single dialysis session of hemodiafiltration with sorbent-regenerated endogenous ultrafiltrate reinfusion (HFR) removes hepcidin more efficiently than bicarbonate hemodialysis: a new approach to containing hepcidin burden in dialysis patients?
Tessitore, N, Poli, A, Bedogna, V, Corazza, L, Campostrini, N, Atti, M, Sereni, L, Castagna, A, Girelli, D, Pessolano, G, et al
Journal of nephrology. 2018;(2):297-306
Abstract
BACKGROUND Most hemodialysis patients have high Hepcidin-25 levels, which may be involved in the pathogenesis of several uremic complications related to an altered iron biology. The hemodialysis procedure itself can influence Hepcidin-25 levels by removing Hepcidin-25 and maybe stimulating its production due to a pro-inflammatory effect. METHODS To assess the relationship between dialysis-related inflammation and intradialysis changes in Hepcidin-25, we performed a crossover trial in 28 hemodialysis patients to compare the effects on serum levels of Hepcidin-25 and inflammatory markers activated during dialysis [Tumor Necrosis Factor-α (TNF-α), Interleukin-6, C-reactive protein (CRP), Pentraxin-3] of a single dialysis session using a technique capable of reducing inflammation, HFR (Hemo Filtrate Reinfusion: a hemodiafiltration system combining convection, diffusion and adsorption) or bicarbonate-dialysis using either the same low-flux membrane as in the diffusion stage of HFR (LFBD) or a high-flux membrane (HFBD). RESULTS HFR achieved a greater reduction in Hepcidin-25 levels than both LFBD [-72% (95% CI: -11 to -133), p = 0.022] and HFBD [-137% (95% CI: -2 to -272), p = 0.047], conceivably due to both a greater removal (because of its convective/adsorptive component) and a lower inflammation-related Hepcidin-25 production. HFR also led to a greater decrease in TNF-α than LFBD [-277% (95% CI: -59 to -494), p = 0.014], while the two methods induced similar changes in Interleukin-6, CRP and Pentraxin-3 levels. CONCLUSIONS Our findings suggest that a single bicarbonate-dialysis session can upregulate Hepcidin-25 synthesis and that HFR can fully overcome this effect, enabling a greater Hepcidin-25 removal during dialysis. Adequately-designed studies are needed, however, to establish whether the beneficial effect of HFR emerging from our study could reduce Hepcidin-25 (and TNF-α) burden and improve clinically-relevant outcomes. TRIAL REGISTRATION ISRCTN15957905.