How to optimize drug delivery in renal replacement therapy.

Drug dosing in the setting of acute kidney injury (AKI) is complicated by several factors such as pharmacokinetic changes in renal failure, inaccuracy of renal estimating equations in this setting, lack of therapeutic drug monitoring capability for most drugs, and use of extracorporeal renal replacement. Pharmacokinetic changes include decreases in protein binding and drug metabolism. Renal estimating equations most often overestimate renal clearance in AKI. Additionally, it is well recognized that some drugs are significantly cleared by extracorporeal therapy. Patients with AKI are therefore at risk for adverse outcomes of drug therapy. It has been reported that approximately half of patients with reduced renal clearance receive drug doses that are 2.5 times higher than the recommended maximum dose. To ensure efficacy and prevent toxicity, therapeutic drug monitoring is highly recommended. However, in the absence of drug monitoring, adequate concentrations can only be inferred from clinical response. A clinician must weigh the risks and benefits of possible over-dosing or under-dosing based on the therapeutic index of the drug and the clinical situation. This article will review the important factors to consider for drug dosing in patients with AKI receiving continuous renal replacement therapy and sustained low-efficiency dialysis.