Decreased thymic output predicts progression of chronic kidney disease

Chronic kidney disease (CKD) is age-related disease, and decreased renal function is associated with the premature aging of T cells and increased incidence of other age-related diseases. However, the relationship between T cell senescence and CKD progression remains unclear. Here, we investigated the relationship between T cell senescence, as indicated by decreased thymic output and increased proportion of highly differentiated CD28^- T cells, and CKD progression.

A total of 175 patients with non-dialysis-dependent CKD were enrolled in this study. Thymic output was assessed based on the CD45RA⁺CD31⁺CD4⁺ cell (recent thymic emigrant [RTE]) counts (RTEs) (/mm³) and the proportion of RTE among CD4⁺ T cells (RTE%). Highly differentiated T cells were assessed based on the proportion of CD28^- cells among CD4⁺ T cells (CD28^-/CD4⁺) and CD28^- cells among CD8⁺ T cells (CD28^-/CD8⁺). The primary outcome was estimated glomerular filtration rate (eGFR) decline of ≥40% or initiation of renal replacement therapy. The association between T cell senescence and renal outcomes was examined using Cox proportional hazards models and restricted cubic splines. The median age was 73 years, 33% were women, and the median eGFR was 26 mL/min/1.73 m². The median RTEs, RTE%, CD28^-/CD4⁺, and CD28^-/CD8⁺ were 97.5/mm³, 16.2, 5.3, and 49.7%, respectively. After a median follow-up of 1.78 years, renal outcomes were observed in 71 patients. After adjusting for age, sex, eGFR, proteinuria, diabetes, and cytomegalovirus seropositivity, decreased RTEs, which corresponded to decreased thymic output, significantly and monotonically increased the risk of poor renal outcome (p = 0.04), and decreased RTE% and increased highly differentiated CD28^-/CD4⁺ T cells also tended to monotonically increase the risk (p = 0.074 and p = 0.056, respectively), but not CD28^-/CD8⁺ T cells.

Decreased thymic output in CKD patients, as well as increased highly differentiated CD4⁺ T cells, predicted renal outcomes. Thus, the identification of patients prone to CKD progression using T cell senescence, particularly decreased RTE as a biomarker, may help to prevent progression to end-stage kidney disease.