Higher serum beta2-microglobulin levels are associated with better survival in chronic hemodialysis patients: a reverse epidemiology

Abstract

beta2-Microglobulin (beta2-M) has been considered a surrogate marker of putative mid-molecular weight (MW) uremic toxins, compounds difficult to dialyze by low-flux dialysis membranes. This study was performed to evaluate the relationship between serum beta2-M and survival of chronic hemodialysis (CHD) patients and the association of beta2-M levels and factors associated with mortality. Part I of this study is a retrospective cohort evaluation that determined the relationship between beta2-M and mortality, and Part II is a cross-sectional study that evaluated the relationship between beta2-M and factors associated with mortality. Laboratory parameters, including beta2-M, albumin, prealbumin, creatinine, blood urea nitrogen (BUN), high-sensitivity C-reactive protein (hs-CRP), lipid battery, KT/V, and normalized protein nitrogen appearance (nPNA), were reviewed in Part I and measured in Part II. Clinical and demographic data, including age, sex, duration of hemodialysis, presence of cardiovascular disease, and presence of diabetes mellitus, were also recorded. Part I: During the follow-up period of 5 years, there were 95 all-cause deaths among the 289 patients. Comparison of survivors and non-survivors indicated that serum beta2-M was higher in survivors (36.8 ± 12.3 vs. 32.6 ± 13.2 µg/ml, p = 0.009). Kaplan-Meier analysis indicated that all-cause mortality in the lower beta2-M group was significantly higher compared to the higher beta2-M group (p < 0.0001). Multivariate Cox regression analyses indicated elevated beta2-M levels were significantly associated with lower mortality rate (relative risk: 0.608; 95% CI: 0.37 to 0.99; p = 0.046). Part II: The mean serum beta2-M concentration was 37.1 ± 14.4 µg/ml. Univariate analysis indicated that beta2-M was positively correlated with nPNA, duration of HD, BMI, and the concentrations of creatinine, albumin, BUN, and hs-CRP, but was negatively correlated with HDL-C concentration. Multiple regression analysis indicated that levels of nPNA (p < 0.001), duration of hemodialysis (p < 0.001), creatinine (p < 0.001), albumin (p = 0.006), BUN (p = 0.011), and HDL-C (p = 0.038) were independently associated with serum beta2-M concentration. Our results showed that higher serum beta2-M levels are associated with better survival in CHD patients and that nutritional status might be an independent predictor of serum beta2-M concentration in these patients.