Related Experiment Video
Updated: Jun 17, 2026

Three-Dimensionally Printed Microfluidic Cross-flow System for Ultrafiltration/Nanofiltration Membrane Performance Testing
Published on: February 13, 2016
Middle-molecule clearance at 20 and 35 ml/kg/h in continuous venovenous hemodiafiltration
1Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Background:
Of 5 clinical trials testing dose response of continuous renal replacement therapy (CRRT) in acute kidney injury, 2 showed a benefit, 2 showed none, and 1 appeared equivocal. However, blood-membrane interactions may dominate macromolecule transport in continuous venovenous hemodiafiltration, reducing the impact of dose adjustment. The dosing arms in the Acute Renal Failure Trial Network (ATN) study may have delivered similar clearances for middle molecules.
Methods:
We simulated the 2 CRRT doses in the ATN study using a synthetic polydisperse macromolecular probe in bovine blood. Clearance of tracers between 10 and 100 kDa molecular weight was measured during 6 h of therapy.
Results:
Middle-molecule clearance differed by less than 2 ml/min between the 2 dosing arms.
Conclusion:
The CRRT prescription used in the ATN study appears to have achieved dose separation for small molecules while holding middle-molecule clearance nearly constant. This may explain the outcome difference between the ATN study and earlier studies, and suggests subsequent trial designs.
Related Concept Videos
Extracorporeal Removal of Drugs: Continuous Renal Replacement Therapy
Extracorporeal Removal of Drugs: Hemoperfusion and Hemofiltration
Continuous Renal Replacement Therapy
Dialysis
Extracorporeal Removal of Drugs: Peritoneal Dialysis and Hemodialysis
Hemodialysis II: Procedure and Complications