ESRD-associated immune phenotype depends on dialysis modality and iron status: clinical implications

Didier Ducloux, Mathieu Legendre, Jamal Bamoulid, Jean-Michel Rebibou, Philippe Saas, Cécile Courivaud, Thomas Crepin, Didier Ducloux, Mathieu Legendre, Jamal Bamoulid, Jean-Michel Rebibou, Philippe Saas, Cécile Courivaud, Thomas Crepin

Abstract

Background: End-stage renal disease (ESRD) causes premature ageing of the immune system. However, it is not known whether hemodialysis (HD) and peritoneal dialysis (PD) similarly affect the T cell system.

Methods: The aim of our study was to analyse whether dialysis modality may mitigate ESRD-induced immune senescence. We explored a large population of patients (675 ESRD patients) and both confirmed and refined the results in a second cohort (84 patients).

Results: HD patients exhibited higher inflammatory monocytes counts (44/mm3 (1-520) vs 36/mm3 (1-161); p = 0.005). Patients on HD also had higher frequency of CD8 T cells (24% (7-61) vs 22% (8-42); p = 0.003) and reduced CD4/CD8 ratio. Such results were confirmed in the second cohort. Moreover, both CD4 + CD57 + CD28- (3.25% (0-38.2) vs 1.05% (0-28.5); p = 0.068) and CD8 + CD57 + CD28- (38.5% (3.6-76.8) vs 26.1 (2.1-46.9); p = 0.039) T cells frequencies were increased in HD patients. Telomere length did not differ according to dialysis modality, but was inversely related to ferritin levels (r = - 0.33; p = 0.003). There was a trend towards higher telomerase activity in PD patients (11 ± 13 vs 6 ± 11; p = 0.053). Thymic function was not different in PD and HD patients. Patients on PD before transplantation had a higher risk of acute rejection after kidney transplantation (HR, 1.61; 95%CI, 1.02 to 2.56; p = 0.041).

Conclusions: More pronounced inflammation with hemodialysis may induce premature aging of the immune system. This observation correlates with a lower risk of acute kidney rejection in patients previously on HD. Clinical consequences in patients maintained on dialysis should be determined.

Trial registration: Trial registration: NCT02843867, registered July 8, 2016.

Keywords: Acute rejection; Dialysis; Immune senescence; Inflammation; Iron overload.

Conflict of interest statement

ORLY-EST study: Sample collection was performed after regulatory approval by the French ministry of health (agreement number # DC-2008-713, June 11th 2009). The ethic committee of Franche-Comté study has approved the study (2008). Patients enrolled in the ORLY-EST study gave their written informed consent. IRIS study: The study was approved by the ethic committee of Franche-Comté (Approval 13/686) and registered in clinicaltrials.gov (NCT02116270). Patients enrolled in the IRIS-EST study gave their written informed consent.NAThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
CD8+ T cell frequency (1a), CD4 + CD45R0 T cell frequency (1b), B cell count (1c), and inflammatory monocytes count (1D) in PD and HD patients. Overall, the results suggest more pronounced inflammation (increased number of inflammatory monocytes) and nonspecific features of immune senescence and/or activation (increased number of CD8+ T cells and CD4 + CD45R0 T cells, and decreased number of B cells) in HD patients compared to PD patients
Fig. 2
Fig. 2
CD4 + CD57 + CD28- (2A) and CD8 + CD57 + CD28- (2B) T cell frequencies in PD and HD patients. Both CD4 + CD57 + CD28- and CD8 + CD57 + CD28- T cell frequencies are increased in HD patients suggesting enhanced replicative senescence
Fig. 3
Fig. 3
Telomere length according to iron status. Telomere length is reduced in patients with iron overload
Fig. 4
Fig. 4
Relationship between ferritin concentrations and telomere length. Telomere length correlates with iron status determined by ferritin levels

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