Pharmacokinetics/Pharmacodynamics

Impaired renal clearance

Decreased renal excretion of drugs during AKI is the most widely applicable change occurring

in critically ill patients. Depending on the patient population and definition used, the incidence

of AKI in ICU patients can be as high as 78%. AKI significantly affects the excretion of

renally eliminated drugs, and dosing modifications must be made in these situations to avoid

potential toxicity.

ii.

The Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines for

AKI recommend that staging of AKI be done using the KDIGO AKI criteria. However, these

guidelines have no specific recommendations regarding drug dosing.

iii.

A clinical update to the 2010 KDIGO guidelines does recommend how to approach drug dosing

in critically ill patients with AKI. Because of the complicated picture of AKI in critically ill

patients, however, these recommendations are not as precise as the recommendations for drug

dosing in CKD. In fact, the authors note that most renal dose adjustment recommendations in

the literature and from the FDA (U.S. Food and Drug Administration) are based on data from

patients with CKD (Kidney Int 2011;80:1122-37).

iv.

The update recommends a stepwise approach to adjusting drug-dosing regimens in patients

with AKI (Box 2).

Box 2. Recommended Steps for Assessing and Adjusting Drug Regimens in Patients with AKI

Step 1 – Assess the following

Demographic information

Medical history (including history of renal disease)

Current clinical information

Current laboratory information

DNA polymorphisms

Step 2 – Estimate GFR (use the best equation according to patient factors)

Age

Body size

Ethnicity

Concomitant diseases

Step 3 – Review current medications

Identify drugs needing individualized dosing

Step 4 – Calculate individualized treatment regimen

Determine treatment goals (PK or PD values)

Calculate dosage regimen (according to drug PK and changes noted in the patient)

Step 5 – Monitor regimen

Drug response

Signs or symptoms of toxicity

Drug concentrations (if available)

Step 6 – Revise regimen

Adjust regimen according to patient response

Adjust regimen according to changes in patient status

AKI = acute kidney injury; GFR = glomerular filtration rate; PD = pharmacodynamic(s); PK = pharmacokinetic(s).