The Shift to the 2021 CKD-EPI Equation for Medication Decision-Making
Key Takeaways
- Cockcroft–Gault historically estimated creatinine clearance for dosing, whereas nephrology advanced through MDRD and earlier CKD-EPI equations for CKD staging using eGFR.
- Eliminating race avoids a non-binary, subjective input and yields a single eGFR value, simplifying medication-related decision-making across populations.
Andrew Bzowyckyj, PharmD, explains the transition to the 2021 CKD-EPI equation and its implications for medication decisions.
The transition from the longstanding Cockcroft-Gault equation to the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation represents a significant shift in how clinicians estimate kidney function for medication-related decision-making. Developed following recommendations from the National Kidney Foundation (NKF) and the American Society of Nephrology (ASN), the 2021 CKD-EPI equation removes race as a variable and is increasingly being adopted by clinical laboratories across the United States.
To discuss the rationale behind the transition, implementation considerations, and practical implications for clinicians, HCPLive spoke with Andrew Bzowyckyj, PharmD, BCPS, CDCES, senior scientific director of Learning Consulting at the National Kidney Foundation, about the evolution of kidney function estimation and what healthcare professionals should know as eGFR-based medication decision-making becomes more widely integrated into clinical practice.
HCPLive: Can you explain the history of the Cockcroft-Gault equation and what has driven the transition toward the 2021 CKD-EPI equation?
Bzowyckyj : The Cockcroft-Gault equation was developed in 1976 to estimate creatinine clearance and was validated in 249 White men. Women were not included in the original validation cohort, and an empiric adjustment was later added based on body size and muscle mass. For decades, that equation became the standard for informing medication dosing in patients with kidney impairment.
At the same time, nephrology was moving toward estimating glomerular filtration rate for chronic kidney disease diagnosis and staging, first with the MDRD equation and later with the CKD-EPI equations.
Today, the 2021 CKD-EPI equation provides an estimate of glomerular filtration rate without incorporating race. Our workgroup's goal is to bridge the historical divide between medication dosing, which has relied on Cockcroft-Gault, and broader medical decision-making, which has relied on eGFR.
We feel clinicians should begin with the best available estimate of a patient's kidney function and then incorporate other patient-specific factors when making medication decisions. The Cockcroft-Gault equation was developed before standardized creatinine assays were widely used, so current eGFR equations better reflect modern clinical practice.
HCPLive: Beyond removing race, what improvements were made in the 2021 CKD-EPI equation, and what has adoption looked like so far?
Bzowyckyj: Removing race from the equation was a major step forward because race is not a binary variable. Eliminating it removes a level of subjectivity from estimating kidney function.
The equation was also developed using much larger and more diverse patient populations, with more than 8000 patients in the derivation cohort and another 4000 in the validation cohort. That provides a much more robust foundation than earlier equations.
We've seen broad adoption, with about two-thirds of clinical laboratories transitioning to the newer race-free equation. Some laboratories are still working through implementation barriers, including software updates and workflow changes.
From a medication standpoint, having one eGFR result for all patients simplifies clinical decision-making because clinicians no longer have to determine which estimate to use based on race.
HCPLive: What should clinicians know as they begin using eGFR for medication-related decisions?
Bzowyckyj: This represents a significant change in practice after decades of relying on Cockcroft-Gault for medication dosing. One important point is that the eGFR reported by the laboratory is standardized to a body surface area of 1.73 m². For medication decisions, clinicians should adjust that value to the patient's actual body surface area because medications are cleared based on an individual's kidney function.
One of our goals at the National Kidney Foundation is to work with electronic health record vendors so these calculations can be automated and presented in a way that's easy for clinicians to use while still allowing them to verify the underlying patient data.
It's also important to remember that every kidney function equation is an estimate. Regardless of which equation is used, the result should serve as a starting point. Clinicians still need to consider the individual patient and other clinical factors when making medication decisions.
Editor’s Note: Bzowyckyj reports no relevant disclosures.
References
Bzowyckyj AS, Nolin TD, Stevens LA, et al. Recommendations for use of the 2021 CKD-EPI creatinine equation for medication-related decision-making. Am J Kidney Dis. 2025;86(5):671-682. doi:10.1053/j.ajkd.2025.05.010
Inker LA, Eneanya ND, Coresh J, et al. New creatinine- and cystatin C-based equations to estimate GFR without race. N Engl J Med. 2021;385(19):1737-1749. doi:10.1056/NEJMoa2102953
