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Riley Larson, PharmD, M Health Fairview Bethesda | Walgreens
Background: In comparison to White patients, Black patients experience worse outcomes in regards to timely nephrology referrals, waitlisting for kidney transplantation, and being less likely to receive sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy. Over the past decade, the 2009 Chronic Kidney Disease Epidemiology Collaboration creatinine (CKD-EPIcr) equation has been used to calculate estimated glomerular filtration rate (eGFR). This equation included"race" (Black or non-Black) as a variable after findings from Levey et. al. deemed the equation more accurate than other commonly used equations at that time. However, Black patients have a higher calculated eGFR than non-Black patients compared to their actual measured GFR, which experts concur may delay access to kidney transplantation and kidney care, such as initiating SGLT2i therapy to stabilize kidney decline. One significant case report outlines a self-identified Black female who could have had a transplant two years sooner if the race variable was not used when calculating her eGFR--despite only having 48% African ancestry per an Ancestry.com genetic test. Therefore, experts from the National Kidney Foundation (NKF) and American Society of Nephrology (ASN) formed a Task Force to reassess the evidence of including race in eGFR. While conducting an evidence-based review, the panel also interviewed a myriad of health professionals, experts, and patients and ultimately recommended immediate implementation of a, re-fitted CKD-EPIcr (2021) equation without a coefficient for race.
Evidence & Discussion: The Task Force explicitly states their evidence-based rationale highlighting that race is a social and not a biological construct, the need to improve the equity of health and social justice, and citing the issues that arise when utilizing race for clinical algorithms (potential implicit and explicit bias). Additionally, the Task Force analyzed a plethora of studies with subsequent modified CKD-EPI equations, taking into consideration six "attributes": Equation performance; patient-centeredness; assay availability and standardization; population diversity in equation development; consequences to clinical care, research, and population tracking; and implementation challenges. Ultimately, the authors found that the re-fitted CKD-EPI equation without a race coefficient would pose minimal challenges in implementation, included diversity in its development, and does not disproportionately affect any group compared to keeping the CKD-EPIcr (2009) equation with the race factor or simply removing race from the CKD-EPIcr (2009).
The recommendation to simply remove race from the current eGFR equations did not go without debate. A 2020 cross-sectional review (also authored by Levey) cautioned against the removal of race from the CKD-EPIcr (2009) equation and reporting the same results for everyone. The authors found eliminating the race coefficient was associated with a systematic bias in underestimation of eGFR in Black individuals. Additionally, Casal et. al. was published shortly after the publication of the Task Force recommendation and also cautioned against removal of race from CKD-EPIcr (2009) eGFR calculations. This study analyzed the eGFR with and without the race variable of Black patients undergoing phase one chemotherapy trials from 1995-2010. Importantly, both of these criticising studies utilized the CKD-EPIcr (2009) equation with or without the removal of race in their data analysis. The Task Force utilized a new, validated CKD-EPIcr (2021) equation without the coefficient of race with slightly adjusted multipliers to mitigate these proposed consequences (see below).
Ultimately, the inclusion of comprehensive studies, formation of a multidisciplinary Task Force across multiple organizations, and consideration of social implications warrant the recommendation to utilize the re-fitted CKD-EPIcr (2021) equation without a race coefficient.
Clinical Impact: Aside from an earlier diagnosis of Chronic Kidney Disease (CKD) and decreased kidney transplant waitlist time in Black individuals, the clinical impact of this recommendation centers around pharmacotherapy adjustments and eligibility. With a decreased eGFR, by utilizing the CKD-EPIcr (2021) equation, Black patients will have expanded access to SGLT-2i initiation, which can slow the progression of kidney disease. In contrast, Black patients may require dose adjustments of certain medications (such as metformin or sulfonylureas). Overall, this change is patient-centered, evidence-based, and may improve equity of health for Black individuals.
CKD-EPIcr (2009) Equation: eGFR = 141 x min(Scr/κ,1)ɑ x max(Scr/κ,1)-1.209 x 0.993age x 1.018 [if female] x 1.159 [if black]
*where Scr is serum creatinine, κ is 0.7 for females and 0.9 for males, ɑ is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/κ or 1, and max indicates the maximum of Scr/κ or 1
CKD-EPIcr (2021) Equation: eGFR = 142 x min(Scr/k,1)ɑ x max(Scr/k,1)-1.200 x 0.9938age x 1.012 [if female]
*where Scr is serum creatinine, k is 0.7 for females and 0.9 for males, ɑ is -0.241 for females and -0.302 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1
Delgado C, Baweja M, Crews DC, et al. A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease [published online ahead of print, 2021 Sep 22]. Am J Kidney Dis. 2021;S0272-6386(21)00828-3. doi:10.1053/j.ajkd.2021.08.003.
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130(6):461-470. doi:10.7326/0003-4819-130-6-199903160-00002.
Delgado C, Baweja M, Burrows NR, et al. Reassessing the Inclusion of Race in Diagnosing Kidney Diseases: An Interim Report from the NKF-ASN Task Force. J Am Soc Nephrol. 2021;32(6):1305-1317. doi:10.1681/ASN.2021010039.
Levey AS, Tighiouart H, Titan SM, Inker LA. Estimation of Glomerular Filtration Rate With vs Without Including Patient Race. JAMA Intern Med. 2020;180(5):793-795. doi:10.1001/jamainternmed.2020.0045
Casal MA, Ivy SP, Beumer JH, Nolin TD. Effect of removing race from glomerular filtration rate-estimating equations on anticancer drug dosing and eligibility: a retrospective analysis of National Cancer Institute phase 1 clinical trial participants. Lancet Oncol. 2021;22(9):1333-1340. doi:10.1016/S1470-2045(21)00377-6.
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.
Jean Moon, PharmD, BCACP, Director
pharmres@umn.edu