Middle-molecule clearance at 20 and 35 ml/kg/h in continuous venovenous hemodiafiltration.

Hofmann CL, Fissell WH
Blood Purif. 2010 29 (3): 259-63

PMID: 20016150 · DOI:10.1159/000266483

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.

Copyright 2009 S. Karger AG, Basel.

MeSH Terms (8)

Acute Kidney Injury Animals Cattle Hemodiafiltration Humans Randomized Controlled Trials as Topic Renal Replacement Therapy Toxins, Biological

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