Decreased renal drug clearance is an obvious consequence of acute kidney injury (AKI). However, there is growing evidence to suggest that nonrenal drug clearance is also affected. Data derived from human and animal studies suggest that hepatic drug metabolism and transporter function are components of nonrenal clearance affected by AKI. Acute kidney injury may also impair the clearance of formed metabolites. The fact that AKI does not solely influence kidney function may have important implications for drug dosing, not only of renally eliminated drugs but also of those that are hepatically cleared. A review of the literature addressing the topic of drug metabolism and clearance alterations in AKI reveals that changes in nonrenal clearance are highly complicated and poorly studied, but they may be quite common. At present, our understanding of how AKI affects drug metabolism and nonrenal clearance is limited. However, based on the available evidence, clinicians should be cognizant that even hepatically eliminated drugs and formed drug metabolites may accumulate during AKI, and renal replacement therapy may affect nonrenal clearance as well as drug metabolite clearance. IntroductionThe incidence of acute kidney injury (AKI) among hospitalized patients is increasing [1,2]. Although this increased incidence may in part be due to critically ill patients representing a larger proportion of patients that are admitted into hospitals and the increased recognition of AKI, this finding is of great concern because AKI has been associated with high rates of in-hospital mortality [3][4][5]. Many developments have occurred over the past several decades that have improved the care provided to patients with AKI, in particular developments relating to renal replacement therapy (RRT). However, our understanding of AKI is continuously evolving, including an appreciation of the changes in drug pharmacokinetics and pharmacodynamics that occur with AKI. Glomerular filtration, tubular secretion, and renal drug metabolism are the processes by which many drugs are removed by the kidneys. It is clear that AKI will affect all of these processes and thus the renal clearance of drugs and toxins. However, what is not well understood is the effect that AKI has on the clearance of these substances by other organ systems (nonrenal clearance). This nonrenal drug clearance typically is dominated by hepatic clearance, but drug metabolism can occur in a variety of organs. Although rarely studied directly, some have observed that nonrenal clearance may change with the onset of AKI (Table 1).Of the drugs summarized in Table 1, particularly vancomycin, none would be considered by clinicians to be drugs with important nonrenal clearances, but nonrenal clearances in AKI have been found to be quite different from those observed in patients with normal renal function or with endstage renal disease. These alterations in nonrenal clearance could be considered 'hidden' drug clearance changes because they usually would go unrecognized. Although it is p...

There is a small but significant association between HL and eGFR. Providers should use HL-tailored communication strategies in CKD patients. Larger multicentre studies are needed to substantiate this relationship.

Daptomycin at 8 mg/kg every 48 hrs in critically ill patients receiving continuous venovenous hemodialysis resulted in good drug exposure, achieved high peak concentrations to maximize daptomycin's concentration-dependent activity, and resulted in trough concentration that would minimize the risk of myopathy. CLINICALTRIALS.GOV IDENTIFIER: NCT00663403.