Online Haemodiafiltration Improves Inflammatory State in Dialysis Patients: A Longitudinal Study

PLoS One. 2016 Oct 26;11(10):e0164969. doi: 10.1371/journal.pone.0164969. eCollection 2016.

Abstract

Background: Patients undergoing conventional hemodialysis (C-HD) present a greater immuno-inflammatory state probably related to uremia, sympathetic nervous system (SNS) activation and /or membrane bioincompatibility, which could improve with a technique-switching to online hemodiafiltration (OL-HD). The antigen-independent pathway activation of this modified immunologic state turns dendritic cells (DC) into an accurate cell model to study these patients. The aim of this study is to further evaluate the immune-inflammatory state of patients in C-HD assessed by DC maturation.

Methods: 31 patients were submitted to C-HD and after 4 months switched to the OL-HD technique. Monocytes-derived DCs from HD patients were cultured in the presence of IL-4/GM-CSF. DC-maturation was evaluated by assessing the maturation phenotype by flow cytometry (FACs). DCs-functional capacity to elicit T-cell alloresponse was studied by mixed leucocyte reaction. Cytokine release was assessed by FACs and SNS was evaluated measuring renalase levels by ELISA.

Results: An up-regulation of maturation markers was observed in C-HD DCs which induced two fold more T cells proliferation than OL-HD DCs. Also, C-HD-mDCs presented with over-production of pro-inflammatory cytokines (IL-6, IL-1β, IL-8, IL-10 and TNF-α) compared with OL-HD-mDC (P<0·05). Results were correlated with clinical data. When SNS was evaluated, hypotension events and blood pressure were significantly lower and renalase levels were significantly higher after conversion to OL-HD. Diabetes mellitus type 2 patients also found beneficial reduction of mDC when converted to OL-HD compared to non-diabetics.

Conclusions: OL-HD could interfere with immuno-inflammatory state in HD patients with an improvement of renalase levels as potential key mediators in the mechanistic pathway of down-regulation of DC maturation.

MeSH terms

  • Aged
  • Cell Proliferation
  • Cytokines / blood
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Diabetes Mellitus / therapy
  • Female
  • Hemodiafiltration / adverse effects*
  • Hemodiafiltration / methods*
  • Humans
  • Inflammation / etiology
  • Inflammation / immunology
  • Inflammation / metabolism
  • Longitudinal Studies
  • Male
  • Monoamine Oxidase / metabolism
  • T-Lymphocytes / cytology
  • Uremia / etiology
  • Uremia / immunology

Substances

  • Cytokines
  • Monoamine Oxidase
  • renalase

Grants and funding

This study was supported by grants from Instituto de Salud Carlos III and Ministerio de Sanidad y Consumo (PI12/01564, PI15/00871) and Fondo Europeo de Desarrollo Regional (FEDER); and Bellvitge Hospital (Ajut HUB 2015, 15PNJ026). This study was also supported by Astellas European Foundation Award (13th European Society of Transplantation). NL is a researcher from ISCIII Miguel Servet (CP06/00067) and REDinREN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.