Abstract
Aim: Loss of renal function is associated with immune deficiency; however, few studies have addressed the role of B lymphocytes in elderly patients with chronic kidney disease (CKD). In this study, we examined the distribution and the relationship of the B lymphocyte subpopulation with clinical outcomes in elderly CKD patients.Methods: In this study, a total of 380 patients (312 CKD patients and 68 non-CKD controls) were recruited. Venous blood samples were analyzed by flow cytometry to determine the following B cell subsets: total B cells (CD19+), innate B1 cells (CD19+CD5+), and conventional B2 cells (CD19+CD5–). Correlations between the B cell subsets with clinical features and patient prognosis were analyzed.Results: A total of 380 patients (mean age 82.29 ± 6.22 years, 76.3% male) were included. The median follow-up time was 37.0 months (range, 1–109 months); 109 (28.7%) patients died. The main causes of death were infections (59.6%) and cardiovascular diseases (22.9%). Correlation analysis showed that levels of serum creatinine (SCr), blood urea nitrogen (BUN), and CKD were negatively associated with B1 cells. However, lymphocytes, T lymphocytes, and estimated glomerular filtration rate (eGFR) were positively correlated with B1 cells (all P < 0.05). B2 cells were negatively associated with age, SCr, cystatin C, BUN, and CKD, and were positively correlated with hemoglobin, lymphocytes, T lymphocytes, NK cells, and eGFR (all P < 0.05). Patient survival was significantly better in patients with B cells > 0.05 × 109/L, B1 cells > 0.02 × 109/L, and B2 cells > 0.04 × 109/L. Multivariate Cox regression analysis showed that B1 cells > 0.02 × 109/L [hazard ratio (HR) = 0.502, 95% confidence interval (CI): 0.297–0.851, P = 0.010] and B2 cells > 0.04 × 109/L (HR = 0.536, 95% CI: 0.319–0.901, P = 0.019) were independent protective factors for all-cause mortality.Conclusions: Our results showed that B1 and B2 cells exhibited a significantly negative correlation with the progression of CKD in elderly patients. Moreover, B1 and B2 cells were independent prognostic factors for survival, which indicates that the decrease in B cells may be associated with the progression of kidney diseases.
Highlights
Reduced renal function is associated with cardiovascular events, infections and death in chronic kidney disease (CKD) patients, and the risk increases when CKD progresses to end-stage renal disease (ESRD) [1]
B2 cells were negatively associated with age (r = −0.150, P = 0.003), serum creatinine (SCr) (r = −0.153, P = 0.003), cystatin C (r = −0.127, P = 0.022), blood urea nitrogen (BUN) (r = −0.158, P = 0.002), and CKD (r = −0.187, P < 0.001), and were positively correlated with hemoglobin (r = 0.105, P = 0.042), lymphocytes (r = 0.596, P < 0.001), T lymphocytes (r = 0.474, P < 0.001), NK cells (r = 0.200, P < 0.001), and the estimated glomerular filtration rate (eGFR) (r = 0.142, P = 0.006)
We found that CKD3 [hazard ratio (HR) = 2.693, 95% confidence interval (CI): 1.116–6.498, P = 0.028], CKD4 (HR = 6.994, 95% CI: 2.708– 18.058, P < 0.001), CKD5 (HR = 5.772, 95% CI: 2.185–15.244, P < 0.001), age (HR = 1.066, 95% CI: 1.022–1.112, P = 0.003), and cystatin C (HR = 1.107, 95% CI: 1.033–1.186, P = 0.004) were factors significantly associated with a higher risk of all-cause mortality
Summary
Reduced renal function is associated with cardiovascular events, infections and death in chronic kidney disease (CKD) patients, and the risk increases when CKD progresses to end-stage renal disease (ESRD) [1]. Immune deficiencies include decreased granulocyte and monocyte/macrophage phagocytic function, defective antigen presentation by monocytes/macrophages, reduced antibody production by B lymphocytes and impaired T-cell-mediated immunity, and they can lead to a low response to vaccination, an increased incidence of microbial infections, tumors, and delayed hypersensitivity [2, 3]. B1 cells predominate in peritoneal and pleural cavities, and they are considered to be elements of the innate immune system and account for 25–27% of peripheral blood B lymphocytes [5]. They produce mainly IgM antibodies that have high crossreactivity but low affinity. B2 cells must differentiate into plasma cells, which are responsible for developing an adaptive response, and they produce diverse and high-affinity antibodies [6]
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