Beta-2 microglobulin and all-cause mortality in the era of high-flux hemodialysis: results from the Dialysis Outcomes and Practice Patterns Study

Background. Beta-2 microglobulin (beta 2M) accumulates in hemodialysis (HD) patients, but its consequences are controversial, particularly in the current era of high-flux dialyzers. High-flux HD treatment improves beta 2M removal, yet beta 2M and other middle molecules may still contribute to adverse events. We investigated patient factors associated with serum beta 2M, evaluated trends in beta 2M levels and in hospitalizations due to dialysis-related amyloidosis (DRA), and estimated the effect of beta 2M on mortality. Methods. We studied European and Japanese participants in the Dialysis Outcomes and Practice Patterns Study. Analysis of DRA-related hospitalizations spanned 1998-2018 (n=23 976), and analysis of beta 2M and mortality in centers routinely measuring beta 2M spanned 2011-18 (n=5332). We evaluated time trends with linear and Poisson regression and mortality with Cox regression. Results. Median beta 2M changed nonsignificantly from 2.71 to 2.65mg/dL during 2011-18 (P=0.87). Highest beta 2M tertile patients (>2.9mg/dL) had longer dialysis vintage, higher C-reactive protein and lower urine volume than lowest tertile patients (<= 2.3mg/dL). DRA-related hospitalization rates [95% confidence interval (CI)] decreased from 1998 to 2018 from 3.10 (2.55-3.76) to 0.23 (0.13-0.42) per 100 patient-years. Compared with the lowest beta 2M tertile, adjusted mortality hazard ratios (95% CI) were 1.16 (0.94-1.43) and 1.38 (1.13-1.69) for the middle and highest tertiles. Mortality risk increased monotonically with beta 2M modeled continuously, with no indication of a threshold. Conclusions. DRA-related hospitalizations decreased over 10-fold from 1998 to 2018. Serum beta 2M remains positively associated with mortality, even in the current high-flux HD era.

Automated summary

The study found a tenfold decrease in DRA-related hospitalization rates from 1998 to 2018. Even in the current era of high-flux HD, serum beta 2M remains positively associated with mortality, with mortality risk increasing monotonically with increasing beta 2M levels.