Dialyzer Classification and Mortality in Hemodialysis Patients: A 3-Year Nationwide Cohort Study

Abstract

Background: Dialyzers are classified as low-flux, high-flux, and protein-leaking membrane dialyzers internationally and as types I, II, III, IV, and V based on β₂-microglobulin clearance rate in Japan. Type I dialyzers correspond to low-flux membrane dialyzers, types II and III to high-flux membrane dialyzers, and types IV and V to protein-leaking membrane dialyzers. Here we aimed to clarify the association of dialyzer type with mortality. Methods: This nationwide retrospective cohort study analyzed data from the Japanese Society for Dialysis Therapy Renal Data Registry from 2010 to 2013. We enrolled 238,321 patients on hemodialysis who were divided into low-flux, high-flux, and protein-leaking groups in the international classification and into type I to V groups in the Japanese classification. We assessed the associations of each group with 3-year all-cause mortality using Cox proportional hazards models and performed propensity score matching analysis. Results: By the end of 2013, 55,308 prevalent dialysis patients (23.2%) had died. In the international classification subgroup analysis, the hazard ratio (95% confidence interval) was significantly higher in the low-flux group [1.12 (1.03-1.22), P = 0.009] and significantly lower in the protein-leaking group [0.95 (0.92-0.98), P = 0.006] compared with the high-flux group after adjustment for all confounders. In the Japanese classification subgroup analysis, the hazard ratios were significantly higher for types I [1.10 (1.02-1.19), P = 0.015] and II [1.10 (1.02-1.39), P = 0.014] but significantly lower for type V [0.91 (0.88-0.94), P < 0.0001] compared with type IV after adjustment for all confounders. These significant findings persisted after propensity score matching under both classifications. Conclusions: Hemodialysis using protein-leaking dialyzers might reduce mortality rates. Furthermore, type V dialyzers are superior to type IV dialyzers in hemodialysis patients.

Keywords: hemodialysis; high-flux dialyzer; low-flux dialyzer; mortality; protein-leaking dialyzer; β2-microglobulin clearance.

Figure 1

Flowchart of study participants.

Figure 2

Kaplan–Meier survival curve for all-cause mortality in the three dialyzer type groups in the international classification.

Figure 3

Hazard ratios for all-cause mortality among the three dialyzer types in 238,321 patients undergoing hemodialysis, determined using standard Cox proportional hazards regression. White bars are adjusted for basic factors, including age, sex, dialysis vintage, presence/absence of diabetes mellitus, and presence/absence of cardiovascular complications. Gray bars are adjusted for dialysis dose, as assessed by Kt/V and β₂-microglobulin levels, in addition to basic factors. Dark gray bars are adjusted for basic factors, dialysis dose, and nutrition- and inflammation-related factors, including body mass index, levels of C-reactive protein, hemoglobin, calcium, phosphate, intact parathyroid hormone, and serum albumin, normalized protein catabolic rate, and percent creatinine generation rate. *P < 0.01, **P < 0.0001 vs. the high-flux dialyzer group (reference). Error bars correspond to 95% confidence intervals.

Figure 4

Kaplan–Meier survival curve for all-cause mortality in the five dialyzer type groups in the Japanese classification.

Figure 5

Hazard ratios for all-cause mortality among the five dialyzer types in 238,321 patients undergoing hemodialysis, determined using standard Cox proportional hazards regression. White bars are adjusted for basic factors, including age, sex, dialysis vintage, presence/absence of diabetes mellitus, and presence/absence of cardiovascular complications. Gray bars are adjusted for dialysis dose, as assessed by Kt/V and β₂-microglobulin levels, in addition to basic factors. Dark gray bars are adjusted for basic factors, dialysis dose, and nutrition- and inflammation-related factors, including body mass index, levels of C-reactive protein, hemoglobin, calcium, phosphate, intact parathyroid hormone, and serum albumin, normalized protein catabolic rate, and percent creatinine generation rate. *P < 0.05, **P < 0.01, ***P < 0.0001 vs. the type IV dialyzer group (reference). Error bars correspond to 95% confidence intervals.

Figure 6

(A) Hazard ratios for all-cause mortality after propensity score matching for the 3 types of dialyzers in the international classification (reference: high-flux dialyzer), determined using Cox proportional hazards regression. *P < 0.05, **P < 0.01 vs. the high-flux dialyzer. Error bars correspond to 95% confidence intervals. (B) Hazard ratios of all-cause mortality after propensity score matching for the 5 types of dialyzers in the Japanese classification (reference: type IV dialyzer), determined using Cox proportional hazards regression. ***P < 0.001 vs. the type IV dialyzer. Error bars correspond to 95% confidence intervals.