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

Ines Rama, Ines Llaudó, Pere Fontova, Gema Cerezo, Carlos Soto, Casimiro Javierre, Miguel Hueso, Nuria Montero, Alberto Martínez-Castelao, Juan Torras, Josep M Grinyó, Josep M Cruzado, Nuria Lloberas, Ines Rama, Ines Llaudó, Pere Fontova, Gema Cerezo, Carlos Soto, Casimiro Javierre, Miguel Hueso, Nuria Montero, Alberto Martínez-Castelao, Juan Torras, Josep M Grinyó, Josep M Cruzado, Nuria Lloberas

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.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Dendritic cell maturation.
Fig 1. Dendritic cell maturation.
A. Modulation of dendritic cell maturation in HD and uremic patients. DCs were obtained from HD and uremic patients and were cultured for 6 days. Expression of cell surface markers was evaluated by flow cytometry and the results were expressed as the percentage of matured DC. B. In the histogram, monocytes are represented in yellow, the immature DC in orange, the matured DC in green and the negative control in grey. MFI and expression of each marker are presented as mean ± SD. C. or Expression of cell surface markers evaluation by the mean fluorescence intensity (MFI) of different maturation markers as CD40, CD80, CD83, CD86, CD54 and HLA-DR in C-HD and OL-HD groups. D. Correlation between DCs maturation and the different convective volumes (D).
Fig 2. OL-HD reduces T-cell proliferation induction…
Fig 2. OL-HD reduces T-cell proliferation induction by DC in the MLR.
A. Lymphocytes were stained with CFSE and exposed to mature DCs (Uremic control vs C-HD vs OL-HD) during 6 days of culture. B. Cell proliferation was determined by flow cytometry after labelling with CD3 antibody.
Fig 3. Cytokine release.
Fig 3. Cytokine release.
A. Different pattern of cytokine release was obtained in OL-HD compared to C-HD. IL-6 and TNFα levels from serum. B. 1β, IL-6, IL-8, IL-10, IL-12p70 and TNFα secretion protein levels from cell supernatant after MLR were measured by cytometric bead array. The results are expressed in pg/ml ± SD.
Fig 4. Renalase release is higher in…
Fig 4. Renalase release is higher in patients following OL-HD than in those following CD-HD.
C-HD and OL-HD patients’ serum renalase levels were measured by ELISA. The results are expressed in ng/ml ± SD.
Fig 5. Correlation of serum renalase levels…
Fig 5. Correlation of serum renalase levels with hypotension events and systolic blood pressure control.

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