A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease

Abstract

Background: In response to a national call for re-evaluation of the use of race in clinical algorithms, the National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) established a Task Force to reassess inclusion of race in the estimation of GFR in the United States and its implications for diagnosis and management of patients with, or at risk for, kidney diseases.

Process deliberations: The Task Force organized its activities over 10 months in phases to ( 1 ) clarify the problem and evidence regarding eGFR equations in the United States (described previously in an interim report), and, in this final report, ( 2 ) evaluate approaches to address use of race in GFR estimation, and ( 3 ) provide recommendations. We identified 26 approaches for the estimation of GFR that did or did not consider race and narrowed our focus, by consensus, to five of those approaches. We holistically evaluated each approach considering six attributes: assay availability and standardization; implementation; population diversity in equation development; performance compared with measured GFR; consequences to clinical care, population tracking, and research; and patient centeredness. To arrive at a unifying approach to estimate GFR, we integrated information and evidence from many sources in assessing strengths and weaknesses in attributes for each approach, recognizing the number of Black and non-Black adults affected.

Recommendations: ( 1 ) For US adults (>85% of whom have normal kidney function), we recommend immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the United States because it does not include race in the calculation and reporting, included diversity in its development, is immediately available to all laboratories in the United States, and has acceptable performance characteristics and potential consequences that do not disproportionately affect any one group of individuals. ( 2 ) We recommend national efforts to facilitate increased, routine, and timely use of cystatin C, especially to confirm eGFR in adults who are at risk for or have CKD, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone. If ongoing evidence supports acceptable performance, the CKD-EPI eGFR-cystatin C (eGFRcys) and eGFR creatinine-cystatin C (eGFRcr-cys_R) refit without the race variables should be adopted to provide another first-line test, in addition to confirmatory testing. ( 3 ) Research on GFR estimation with new endogenous filtration markers and on interventions to eliminate race and ethnic disparities should be encouraged and funded. An investment in science is needed for newer approaches that generate accurate, unbiased, and precise GFR measurement and estimation without the inclusion of race, and that promote health equity and do not generate disparate care.

Implementation: This unified approach, without specification of race, should be adopted across the United States. High-priority and multistakeholder efforts should implement this solution.

Graphical abstract

Figure 1.

Process and input to create a unifying approach to GFR estimation was comprehensive. Sources (blue arrows) used to identify and evaluate attributes (boxes) of 26 approaches. Each source provided information about multiple topics: equity and disparities; race and racism; GFR measurement, estimation, and equation performance; laboratory standardization; consequences; patient perspectives; and new science. Information was integrated by the Task Force in its considerations of the attributes during deliberations to arrive at a unifying approach.

Figure 2.

Performance of approaches CKD-EPIcr, CKD-EPIcr_NB, CKD-EPIcr_R, CKD-EPIcr-cys, CKD-EPIcr-cys_NB, CKD-EPIcr-cys_R, and CKD-EPIcys compared was examined with mGFR for Black and non-Black adults. (Left six panels) Bias as shown as median difference between mGFR and eGFR. Units are milliliters per minute per 1.73 m². A positive number indicates underestimate of mGFR and a negative number indicates overestimate of mGFR. Solid gray line is the line of identity. Dashed gray lines are drawn at the median difference of 5 and −5 ml/min per 1.73 m², which is defined as a small bias (shown in Table 2). (Right six panels) Accuracy as shown as percentage of estimates >30% of mGFR (1−P₃₀). Dashed gray lines are drawn at 1−P₃₀ of 10%, which is the definition of small inaccuracy (greatest accuracy), as shown in Table 2. For all panels, the left column shows results for Black adults and the right column shows results as modified from Inker et al.

Figure 3.

Estimated number of US Black and non-Black adults is larger at higher eGFR categories according to approaches CKD-EPIcr, CKD-EPIcr_NB, CKD-EPIcr_R, CKD-EPIcr-cys, CKD-EPIcr-cys_NB, CKD-EPIcr-cys_R, and CKD-EPIcys. Using serum creatinine or cystatin C, GFR was estimated from 4563 participants (≥20 years) from the 1999–2000 and 2001–2002 cycles of National Health and Nutrition Examination Surveys. Prevalence estimates for eGFR categories as shown were applied to the 2019 US estimate of 246.6 million adults aged ≥20 years. Units of GFR are in milliliters per minute per 1.73 m². Data are shown in Inker et al. Results are consistent with Duggal et al., Diao et al., and Walther et al. for approach CKD-EPIcr_NB. For approach names, see Table 1.