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

Abstract

Background. Beta-2 microglobulin (β2M) accumulates in hemodialysis (HD) patients, but its consequences are controversial, particularly in the current era of high-flux dialyzers. High-flux HD treatment improves β2M removal, yet β2M and othermiddle moleculesmay still contribute to adverse events.We investigated patient factors associated with serumβ2M, evaluated trends in β2Mlevels and in hospitalizations due to dialysis-related amyloidosis (DRA), and estimated the effect of β2M 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 β2M andmortality in centers routinelymeasuring β2Mspanned 2011-18 (n=5332).We evaluated time trends with linear and Poisson regression and mortality with Cox regression. Results. Median β2M changed nonsignificantly from 2.71 to 2.65 mg/dL during 2011-18 (P=0.87). Highest β2M tertile patients (>2.9 mg/dL) had longer dialysis vintage, higher C-reactive protein and lower urine volume than lowest tertile patients (≤2.3 mg/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 β2M 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 β2M modeled continuously, with no indication of a threshold. Conclusions. DRA-related hospitalizations decreased over 10-fold from 1998 to 2018. Serum β2M remains positively associated with mortality, even in the current high-flux HD era.