Pragmatic Use of Kidney Function Estimates for Drug Dosing: The Tide Is Turning

Abstract

Creatinine clearance has been the most common method of estimating kidney function for the purpose of drug dosing for decades. The availability and extensive clinical use of estimated glomerular filtration rate (eGFR) now provides clinicians a potential alternative. Currently, data demonstrating the validity of eGFR-based drug dosing is limited, but proof of principle has been established and the tide related to use of eGFR for drug dosing appears to be turning. Use of the same kidney function estimate for management of kidney disease, drug development and dosing, and harmonization in all clinical arenas would be ideal. Use of multiple equations can lead to differences in kidney function estimates and corresponding drug dosing regimens, which necessitates clinical judgment and a pragmatic approach when rendering drug dosing decisions. Careful consideration of the risk-benefit ratio of individual drugs and dosing regimens within each patient is warranted. Going forward, FDA guidance will likely incentivize pharmaceutical manufacturers to generate eGFR-based dosing recommendations in addition to creatinine clearance for inclusion in the label of newly approved drugs. However, dosing information for currently approved drugs will continue to be based on creatinine clearance alone, so clinicians must be vigilant in the assessment of kidney function in order to provide optimal pharmacotherapy.

Keywords: Creatinine clearance; Cystatin C; Drug dosing; Estimated glomerular filtration rate; Pharmacokinetics.