Methods of Estimating Kidney Function for Drug Dosing in Special Populations

International guidelines recommend the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method to monitor kidney function in chronic kidney disease using either creatinine- or cystatin C-based estimation methods. The choice of an estimation method to determine dosage for renally eliminated drugs is not as clear. For the majority of currently marketed drugs, the Cockcroft-Gault equation with the Jaffe method, a non-isotope dilution mass spectrometry, standardized serum creatinine, was used to estimate kidney function to recommend dosing adjustment in kidney impairment. As the Cockcroft-Gault equation cannot be converted for isotope dilution mass spectrometry-traceable creatinine values and clinical laboratories now report estimated glomerular filtration (eGFR) rate by the Modified Diet in Renal Disease (MDRD) Equation or CKD-EPI, the eGFR is now more widely accepted for dosage adjustment recommendations. Cockcroft-Gault, MDRD Equation, and CKD-EPI creatinine-based methods were developed in specific populations, which included either none or a low proportion of obese individuals, pregnant women, older adults, and those with significant comorbid conditions. Clinical studies in these special populations have identified significant decreased accuracy, precision, and bias in the creatinine-based methods. Newer cystatin C-based estimation methods may significantly improve the ability to estimate kidney function to determine doses in the future. At this time, the increased cost and lack of standardization of serum cystatin C hinder routine use.