title: Dialyzer Reuse and Outcomes of High Flux Dialysis.
abstract: BACKGROUND
  The bulk of randomized trial evidence for the expanding use of High Flux (HF) hemodialysis worldwide comes from two randomized controlled trials, one of which (HEMODIALYSIS, HEMO) allowed, while the other (Membrane Outcomes Permeability, MPO) excluded, the reuse of membranes. It is not known whether dialyzer reuse has a differential impact on outcomes with HF vs low flyx (LF) dialyzers.
  
  
  METHODS
  Proportional Hazards Models and Joint Models for longitudinal measures and survival outcomes were used in HEMO to analyze the relationship between β2-microglobulin (β2M) concentration, flux, and reuse. Meta-analysis and regression techniques were used to synthesize the evidence for HF dialysis from HEMO and MPO.
  
  
  RESULTS
  In HEMO, minimally reused (< 6 times) HF dialyzers were associated with a hazard ratio (HR) of 0.67 (95% confidence interval, 95%CI: 0.48-0.92, p = 0.015), 0.64 (95%CI: 0.44 - 0.95, p = 0.03), 0.61 (95%CI: 0.41 - 0.90, p = 0.012), 0.53 (95%CI: 0.28 - 1.02, p = 0.057) relative to minimally reused LF ones for all cause, cardiovascular, cardiac and infectious mortality respectively. These relationships reversed for extensively reused membranes (p for interaction between reuse and flux < 0.001, p = 0.005) for death from all cause and cardiovascular causes, while similar trends were noted for cardiac and infectious mortality (p of interaction between reuse and flux of 0.10 and 0.08 respectively). Reduction of β2M explained only 1/3 of the effect of minimally reused HF dialyzers on all cause mortality, while non-β2M related factors explained the apparent attenuation of the benefit with more extensively reused dialyzers. Meta-regression of HEMO and MPO estimated an adjusted HR of 0.63 (95% CI: 0.51-0.78) for non-reused HF dialyzers compared with non-reused LF membranes.
  
  
  CONCLUSIONS
  This secondary analysis and synthesis of two large hemodialysis trials supports the widespread use of HF dialyzers in clinical hemodialysis over the last decade. A mechanistic understanding of the effects of HF dialysis and the reuse process on dialyzers may suggest novel biomarkers for uremic toxicity and may accelerate membrane technology innovations that will improve patient outcomes.
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University of New Mexico, Albuqurque, New Mexico, United States of America.
authors.forename: Christos
authors.initials: C
authors.lastname: Argyropoulos
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University of New Mexico, Albuqurque, New Mexico, United States of America.
authors.forename: Maria-Eleni
authors.initials: ME
authors.lastname: Roumelioti
authors.affiliation: Department of Epidemiology and Biostatistics School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Abdus
authors.initials: A
authors.lastname: Sattar
authors.affiliation: Department of Critical Care Medicine, CRISMA Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
authors.affiliation: Department of Critical Care Medicine, CRISMA Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Biostatistics University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Lisa
authors.initials: L
authors.lastname: Weissfeld
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University of New Mexico, Albuqurque, New Mexico, United States of America.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Unruh
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D008567:Membranes, Artificial; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D008962:Models, Theoretical; D010539:Permeability; D006435:Renal Dialysis / Q000295:instrumentation* / Q000401:mortality; D016019:Survival Analysis; D016896:Treatment Outcome; D001613:beta 2-Microglobulin / Q000032:analysis
chemical_list: D008567:Membranes, Artificial; D001613:beta 2-Microglobulin