Why Drug Dosing in Acute Kidney Injury Is So Hard to Get Right

In an interview with Pharmacy Times, Erin Barreto, PharmD, PhD, RPh, BCCCP, associate professor of medicine and pharmacy at Mayo Clinic in Rochester and a critical care pharmacist whose research focuses on optimizing renally active medications, discussed why medication dosing in acute kidney injury (AKI) is so challenging and how the risks of dosing errors vary.

Barreto presented these insights during a presentation at the American Society of Nephrology’s 2026 Kidney Week, which took place October 21–25 in Denver, Colorado.

Barreto explained that AKI presents an exceedingly dynamic clinical situation, yet clinicians rely on tools that cannot adequately capture its physiology or pharmacokinetics. Creatinine, the long-standing foundation of kidney function assessment, has well-recognized limitations, including non-renal determinants and a kinetic profile that become especially problematic in critically ill patients. As a result, she said, clinicians are often behind when it comes to dose optimization.

Barreto emphasized that this challenge cuts both ways. Undetected kidney decline can lead to drug accumulation, such as supratherapeutic vancomycin concentrations, while undetected renal recovery can cause dramatic underexposure to medications such as levetiracetam (Keppra; UCB Pharma), potentially resulting in a breakthrough seizure.

On the risks of overdosing versus underdosing, Barreto said the answer is entirely patient- and drug-specific. In adult critical care, where high-risk, high-reward medications are used to save lives, willingness to accept risk may be somewhat higher. In hematology/oncology, narrow therapeutic windows mean both undertreatment and excessive toxicity can be life-threatening, and pediatric and neonatal patients also face substantial risk. For pharmacists, appraising that risk means weighing the drug, its therapeutic window, and the vulnerability of the patient.