Akademska digitalna zbirka SLovenije - logo
E-viri
Celotno besedilo
Recenzirano Odprti dostop
  • Uraemia-induced immune sene...
    Crépin, Thomas; Legendre, Mathieu; Carron, Clémence; Vachey, Clément; Courivaud, Cécile; Rebibou, Jean-Michel; Ferrand, Christophe; Laheurte, Caroline; Vauchy, Charline; Gaiffe, Emilie; Saas, Philippe; Ducloux, Didier; Bamoulid, Jamal

    Nephrology, dialysis, transplantation, 04/2020, Letnik: 35, Številka: 4
    Journal Article

    Abstract Background Patients with chronic kidney disease (CKD) are more prone to develop premature age-related diseases. Data on immune senescence are scarce in CKD populations, except in end-stage renal disease and dialysis. We designed a longitudinal prospective study to evaluate immune senescence at different CKD stages and its influence on CKD patient outcomes. Methods Clinical and biological data collections were performed on 222 patients at different CKD stages 1–2 (n = 85), 4 (n = 53) and 5 (n = 84). Immune senescence biomarkers were measured by cytometry on T cells (CD28, CD57, CD45RA, CD31, γH2A.X) or by quantitative polymerase chain reaction relative telomere length (RTL) on peripheral blood mononuclear cells and analysed according to CKD stages and outcomes. Results CKD was associated with an increase in immune senescence and inflammation biomarkers, as follows: low thymic output (197 ± 25 versus 88 ± 13 versus 73 ± 21 CD4+CD45RA+CD31+ T cells/mm3), an increased proportion of terminally differentiated T cells (CD8+CD28−CD57+) (24 ± 18 versus 32 ± 17 versus 35 ± 19%) restricted to cytomegalovirus-positive patients, telomere shortening (1.11 ± 0.36 versus 0.78 ± 0.24 versus 0.97 ± 0.21 telomere:single copy ratio) and an increase in C-reactive protein levels median 2.9 (range 1.8–4.9) versus 5.1 (27–9.6) versus 6.2 (3.4–10.5) mg/L. In multivariate analysis, shorter RTL was associated with death {hazard ratio HR 4.12 95% confidence interval (CI) 1.44–11.75}. Low thymic output was associated with infections HR 1.79 (95% CI (1.34–9.58) and terminally differentiated CD8+ T-cell expansion with a risk of cardiovascular events CEs; HR 4.86 (95% CI 1.72–13.72). Conclusion CKD was associated with premature immune ageing. Each of these alterations increased the risk of specific age-related diseases, such as RTL and death, thymic function and infections and terminally differentiated CD8+ T-cell expansion and CEs.