Decreased B1 and B2 Lymphocytes Are Associated With Mortality in Elderly Patients With Chronic Kidney Diseases

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.

Keywords: B cells; chronic kidney disease; correlation; elderly; prognosis.

Figure 1

Flow cytometric analysis of lymphocytes, including T lymphocytes (CD3+), NK cells (CD3–CD16+CD56+), and B lymphocytes (CD19+). B cells were divided into B1 and B2 cells according to the surface expression of CD5+, CD19+CD5+ (innate B1 cells), and CD19+CD5– (conventional B2 cells).

Figure 2

Kaplan–Meier survival curves of CD19+ B lymphocytes, CD19+CD5+ B1 lymphocytes, and CD19+CD5– B2 lymphocytes in the total cohort (A, E, I), control group (B, F, J), CKD1–3 group (C, G, K), and CKD4–5 group (D, H, L). CD19+ B lymphocytes were divided into two groups: low: ≤ 0.05 × 10⁹/L and high: >0.05 × 10⁹/L; CD19+CD5+ B1 lymphocytes were divided into two groups: low: ≤ 0.02 × 10⁹/L and high: >0.02 × 10⁹/L; CD19+CD5– B2 lymphocytes were divided into two groups: low: ≤ 0.04 × 10⁹/L and high: >0.04 × 10⁹/L.