Intradialytic kinetics of middle molecules during hemodialysis and hemodiafiltration

Nephrol Dial Transplant. 2019 May 1;34(5):870-877. doi: 10.1093/ndt/gfy304.


Background: The kinetics of β2-microglobulin during hemodialysis and hemodiafiltration is well described by a two-compartment model where clearance by the dialyzer is from a central compartment volume that approximates plasma volume and a total distribution volume that approximates extracellular fluid volume. The kinetics of middle molecules with molecular weights larger than β2-microglobulin have not been extensively studied.

Methods: Intradialytic plasma concentrations and overall dialyzer clearances of β2-microglobulin (11.8 kD), myoglobin (16.7 kD) and complement factor D (24.4 kD) were used to estimate three kinetic parameters from a two-compartment model, namely intercompartmental clearance, central compartment volume and total distribution volume, in hemodialysis patients; these data were collected during two clinical trials of medium cut-off dialyzers (with extended middle molecule removal) during hemodialysis and high-flux dialyzers during hemodialysis and hemodiafiltration. In the current exploratory analyses, the kinetic parameters from all dialyzers were combined. Overall dialyzer clearance was evaluated by total mass removed in the dialysate.

Results: In total, 345 sets of kinetic parameters from 35 patients were determined. Intercompartmental clearance and central compartment volume for myoglobin and complement factor D were smaller (P < 0.001) than those for β2-microglobulin. Independent of middle molecule, intercompartmental clearance and central compartment volume were associated with overall dialyzer clearance (P < 0.001), but total distribution volume was not (P = 0.083).

Conclusions: A two-compartment kinetic model can only describe intradialytic kinetics of middle molecules with molecular weights larger than β2-microglobulin if the central compartment is small and dependent on overall dialyzer clearance.

Keywords: clearance; compartment model; hemodialysis; medium cut-off dialyzers; middle molecules.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Complement Factor D / metabolism
  • Cross-Over Studies
  • Dialysis Solutions / pharmacokinetics*
  • Hemodiafiltration / methods
  • Humans
  • Prospective Studies
  • Renal Dialysis / methods*
  • Uremia / metabolism
  • Uremia / therapy*
  • beta 2-Microglobulin / metabolism*


  • Biomarkers
  • Dialysis Solutions
  • beta 2-Microglobulin
  • CFD protein, human
  • Complement Factor D