Abstract
Patients with end-stage renal disease (ESRD) are at high risk of morbidity and mortality from cardiovascular and infectious diseases, which have been found to be associated with a disturbed immune response. Accelerated T-cell senescence is prevalent in these patients and considered a significant factor contributing to increased risk of various morbidities. Nevertheless, few studies have explicated the relevance of T-cell senescence to these fatal morbidities in ESRD patients. In this study, we designed a longitudinal prospective study to evaluate the influence of T-cell senescence on cardiovascular events (CVEs) and infections in hemodialysis (HD) patients. Clinical outcomes of 404 patients who had been on HD treatment for at least 6 months were evaluated with respect to T-cell senescence determined using flow cytometry. We found that T-cell senescence was associated with systemic inflammation. High-sensitivity C-reactive protein was positively associated with decreased naïve T cell levels. Elevated tumor necrosis factor-α and interleukin 6 levels were significantly associated with lower central memory T cell and higher T effector memory CD45RA cell levels. Decreased CD4+ naïve T cell count was independently associated with CVEs, whereas decreased CD8+ naïve T cell count was independently associated with infection episodes in HD patients. In conclusion, HD patients exhibited accelerated T-cell senescence, which was positively related to inflammation. A reduction of naïve T cell could be a strong predictor of CVEs and infection episodes in HD patients.
Highlights
End-stage renal disease (ESRD), considered as a public health concern, affects more than 1.5 million people worldwide [1]
It has been proposed that chronic kidney disease may be a model of premature aging, since uremia could induce premature senescence and many aging-related complications are prevalent in ESRD patients, including those with cardiovascular diseases (CVDs) and infections [4]
CD4+ naïve T cells is a strong predictor of cardiovascular events (CVEs), while a decreased level of CD8+ naïve T cells is a strong predictor of infectious episodes in HD patients
Summary
End-stage renal disease (ESRD), considered as a public health concern, affects more than 1.5 million people worldwide [1]. It has been proposed that chronic kidney disease may be a model of premature aging, since uremia could induce premature senescence and many aging-related complications are prevalent in ESRD patients, including those with cardiovascular diseases (CVDs) and infections [4]. T cells in ESRD patients are preactivated by secreting more inflammatory cytokines in the resting state, leading to persistent inflammation and providing a breeding ground for CVD [8, 9]. T cells in ESRD patients have diminished reaction toward pathogen stimulation, with susceptibility to apoptotic death after activation [9], reduced humoral response to vaccination [10], and impaired maintenance of specific T cell memory [11], resulting in a high incidence of infection. Interventions targeting T cell function could improve morbidity and mortality in such patients
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