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. 2023 Feb 1;34(2):309-321.
doi: 10.1681/ASN.2022070818. Epub 2022 Nov 11.

National Projections for Clinical Implications of Race-Free Creatinine-Based GFR Estimating Equations

James A Diao  1   2 , Gloria J Wu  1   2 , Jason K Wang  1   2 , Isaac S Kohane  1 , Herman A Taylor  3 , Hocine Tighiouart  4 , Andrew S Levey  5 , Lesley A Inker  5 , Neil R Powe  6 , Arjun K Manrai  1   2
Affiliations

National Projections for Clinical Implications of Race-Free Creatinine-Based GFR Estimating Equations

James A Diao et al. J Am Soc Nephrol. .

Abstract

Background: The National Kidney Foundation and American Society of Nephrology Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease recently recommended a new race-free creatinine-based equation for eGFR. The effect on recommended clinical care across race and ethnicity groups is unknown.

Methods: We analyzed nationally representative cross-sectional questionnaires and medical examinations from 44,360 participants collected between 2001 and 2018 by the National Health and Nutrition Examination Survey. We quantified the number and proportion of Black, White, Hispanic, and Asian/Other adults with guideline-recommended changes in care.

Results: The new equation, if applied nationally, could assign new CKD diagnoses to 434,000 (95% confidence interval [CI], 350,000 to 517,000) Black adults, reclassify 584,000 (95% CI, 508,000 to 667,000) to more advanced stages of CKD, restrict kidney donation eligibility for 246,000 (95% CI, 189,000 to 303,000), expand nephrologist referrals for 41,800 (95% CI, 19,800 to 63,800), and reduce medication dosing for 222,000 (95% CI, 169,000 to 275,000). Among non-Black adults, these changes may undo CKD diagnoses for 5.51 million (95% CI, 4.86 million to 6.16 million), reclassify 4.59 million (95% CI, 4.28 million to 4.92 million) to less advanced stages of CKD, expand kidney donation eligibility for 3.96 million (95% CI, 3.46 million to 4.46 million), reverse nephrologist referral for 75,800 (95% CI, 35,400 to 116,000), and reverse medication dose reductions for 1.47 million (95% CI, 1.22 million to 1.73 million). The racial and ethnic mix of the populations used to develop eGFR equations has a substantial effect on potential care changes.

Conclusion: The newly recommended 2021 CKD-EPI creatinine-based eGFR equation may result in substantial changes to recommended care for US patients of all racial and ethnic groups.

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Conflict of interest statement

A.S. Levey reports receiving research funding from grants and contracts paid to Tufts Medical Center from NIH and NKF; reports contracts to paid from AstraZeneca (Data and Safety Monitoring Board (DSMB) for dapagliflozin trials); and reports receiving honoraria from academic medical centers for visiting professorships. H.A. Taylor reports having consultancy agreements with Pfizer, Novartis, and United Health Group (UHG); reports receiving research funding from 23andMe and UHG; and reports receiving honoraria from Pfizer, Novartis, and UHG. I.S. Kohane reports having consultancy agreements with Danaher; reports having an ownership interest in Activate Care, Canary Medical, and Inovalon; reports receiving honoraria from Janssen; and reports having an advisory or leadership role with Activate Care, Canary Medical, and Inovalon. J.K. Wang reports employment with PathAI; and having consultancy agreements with Prometheus Biosciences. L.A. Inker reports having consultancy agreements with Diamtrix; receiving research funding from to institute for research and contracts with the Chinnocks, NIH, NKF, Omeros, and Reata Pharmaceuticals; reports having consulting agreements with Tricida Inc.; reports having an advisory or leadership role with the Alport Foundation Medical Advisory Council and the NKF Scientific Advisory Board; and reports having other interests or relationships as an American Society of Nephrology member and an NKF member. N.R. Powe reports having an advisory or leadership role with Hennepin Health Care Research Institute, Patient Centered Outcomes Research Institute, Portland VA Research Foundation, Robert Wood Johnson Foundation, University of Washington, and Vanderbilt University. Because N.R. Powe is an associate editor of the Journal of the American Society of Nephrology, he was not involved in the peer review process for this manuscript. A guest editor oversaw the peer review and decision-making process for this manuscript. All remaining authors have nothing to disclose.

Figures

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Graphical abstract
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(A) Density functions for the eGFR in US adults when computed using the 2021 CKD-EPI equation and the 2006 MDRD equation. Estimates were survey weighted to be representative of the 2001–2018 US population. (B) Histogram for the change in estimated GFR in US adults when switching from the 2006 MDRD equation to the 2021 CKD-EPI equation.
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(C) and (D) Same as (A) and (B), but modeling a switch from the 2009 CKD-EPI equation to the 2021 CKD-EPI equation.
Figure 2
Figure 2
Differences in CKD status and stage by race and ethnicity with new and prior GFR estimating equations. (A) Change in CKD disease burden by age group colored by eGFR category when switching from the 2009 CKD-EPI and 2006 MDRD equations to the 2021 CKD-EPI equation. CKD is defined as eGFR<60 ml/min per 1.73 m2 or urine albumin-creatinine ratio >30 mg/g without the chronicity requirement. (B) Crude prevalence of CKD derived using the 2021 CKD-EPI equation, the 2009 CKD-EPI equation, and the 2006 MDRD equation. Error bars represent 95% CIs. Estimates from NHANES were survey weighted to be representative of the 2001–2018 US population.
Figure 3
Figure 3
Changes in clinical recommendations for US adults with new and prior GFR estimating equations. The projected number of US adults who would be recommended for changes in clinical care after adoption of the 2021 CKD-EPI equation when switching from the 2009 CKD-EPI equation or the 2006 MDRD equation. Drug classes are defined in the Methods. Percentage labels, shown for changes from 2006 MDRD only, reflect the relative increase or decrease in the number of adults with recommended contraindications or dose reductions in these drug classes, namely, (# with new equation − # with prior equation)/(# with prior equation). Recommendations are from KDIGO or the AAFP. Pharmacologic recommendations are only computed for patients who are currently taking that medication. Data from NHANES from 2001 to 2018; estimates, and their confidence intervals were adjusted using NHANES design and weights to be representative of the US population.
Figure 4
Figure 4
Enrichment of Black participants in development data for eGFR equations affects prevalence of CKD and pharmacologic recommendations. (A) Prevalence of CKD. (B) Number of individuals with recommended dose reduction for a drug they are currently taking, shown against proportion of Black participants for five race-free equations. Candidate equations were developed using the CKD-EPI cohort with non-Black individuals resampled to the given proportion of Black participants. Equations developed using greater proportions of Black participants resulted in lower prevalence of CKD and fewer individuals with recommended dose reductions among all race and ethnicity groups.
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Comment in

  • GFR, Race, and Implications.
    Goldsmith D. Goldsmith D. J Am Soc Nephrol. 2023 Apr 1;34(4):721. doi: 10.1681/ASN.0000000000000096. J Am Soc Nephrol. 2023. PMID: 37000954 Free PMC article. No abstract available.
  • Author Reply: GFR, Race, and Implications.
    Delgado C. Delgado C. J Am Soc Nephrol. 2023 Apr 1;34(4):721-722. doi: 10.1681/ASN.0000000000000097. J Am Soc Nephrol. 2023. PMID: 37000955 Free PMC article. No abstract available.

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