Hemodiafiltration Mechanism in End-Stage Renal Disease
Hemodiafiltration (HDF) combines both diffusive and convective clearance mechanisms in a single treatment modality, using a highly permeable dialyzer membrane to remove uremic toxins through diffusion (like standard hemodialysis) while simultaneously employing convective transport via ultrafiltration and replacement with sterile substitution fluid. 1, 2
Core Mechanisms of Hemodiafiltration
Dual Clearance Process
Diffusive clearance removes small molecular weight compounds (such as urea and creatinine) through concentration gradient-driven transport across the dialyzer membrane, similar to conventional hemodialysis 1, 2
Convective clearance enhances removal of middle and large molecular weight uremic toxins through solvent drag, where plasma water and dissolved solutes are transported across the highly permeable membrane by hydrostatic pressure 1, 2
The combination of these two mechanisms enlarges the spectrum of uremic compounds cleared, extending from small molecular weight compounds up to middle and large molecular weight molecules that are poorly removed by diffusion alone 2
Substitution Fluid Production and Delivery
On-line HDF (OL-HDF) produces substitution fluid through "cold sterilization" via ultrafiltration of ultrapure dialysis fluid, providing unlimited amounts of sterile, non-pyrogenic IV-grade solution at low cost 1, 2
Substitution fluid can be infused at different sites relative to the dialyzer:
- Post-dilution HDF: Fluid added after the dialyzer, offering the most efficient combination of diffusive and convective clearances 1
- Pre-dilution HDF: Fluid added before the dialyzer, useful when high filtration rates are difficult to achieve due to hemorheological conditions 1
- Mixed dilution: Combination of pre- and post-dilution at various percentages to optimize clearance while managing blood viscosity 1, 2
Membrane Characteristics
HDF requires highly permeable (high-flux) dialyzer membranes with large pore sizes to facilitate convective transport of larger molecular weight solutes 2
The increased internal filtration process combined with more open membranes allows for enhanced removal of uremic retention solutes across a broad molecular weight spectrum 2
Clinical Relevance and Dose Considerations
Convective Volume as Dose Indicator
The convective dose in HDF is measured by the substitution volume delivered per session, with emerging evidence suggesting that high convective volumes (≥17 liters per session) are associated with survival benefits compared to lower volumes 3
The dialytic convective dose can be adjusted to individual patient needs by selecting the appropriate substitution modality (post, pre, or mixed-HDF) 2
Biocompatibility Advantages
Regular use of ultrapure dialysis fluid required for HDF improves biocompatibility of the extracorporeal circuit, reducing inflammatory responses compared to conventional hemodialysis 2
This reduced inflammatory burden may contribute to improved patient outcomes beyond the enhanced solute clearance 2
Common Pitfalls and Practical Considerations
Hemorheological limitations: High hematocrit levels (from improved anemia correction) can make high filtration rates difficult to achieve in post-dilution mode, necessitating use of pre-dilution or mixed-dilution strategies 1
Transmembrane pressure monitoring: Excessive transmembrane pressure during high convective volume HDF can compromise filter performance and should be monitored 1
Volume-dependent effects: The survival benefit of HDF appears to be volume-dependent, with patients receiving lower substitution volumes showing no clear advantage over conventional hemodialysis 3
Infection risk considerations: While HDF offers potential mortality benefits, high-flux hemodialysis has been associated with reduced infection-related mortality compared to HDF in some analyses 4