Skip to content

Race and the eGFR equation

TL;DR — Race-free 2021 CKD-EPI equations removed a social category from creatinine-based eGFR; the creatinine-cystatin C equation was more accurate than either marker alone (Inker 2021, PMID 34554658). The NKF-ASN task force recommended immediate implementation of the new creatinine equation and wider cystatin C use (Delgado 2022, PMID 34563581). Reclassification can alter CKD staging, drug eligibility, referral and transplant timing, so implementation should be audited as a clinical intervention. Removing race from an equation does not remove structural inequity in who is tested, referred or treated (Cusick 2025, PMID 40227684).

What changed

The earlier US equation assigned different estimates to people labelled Black. The 2021 equations excluded race and refit coefficients using contemporary cohorts (Inker 2021, PMID 34554658).

Accuracy is not one number

Bias, precision and correct classification vary across GFR levels and populations. The combined creatinine-cystatin C equation performed better overall, but cystatin C access is uneven (Inker 2021, PMID 34554658).

Equity rationale

The task force treated race as a social rather than biological construct and sought a uniform approach while preserving safety and access (Delgado 2022, PMID 34563581).

Downstream consequences

A lower or higher reported eGFR can move referral, contrast, drug-dosing and transplant thresholds. Direction and magnitude depend on the old equation, population and decision threshold.

What did not change

Albuminuria remains an independent kidney-damage and risk marker. Equation reform cannot substitute for uACR testing (CKD Prognosis Consortium 2023, PMID 37787795).

Audit requirements

Systems should measure changes in CKD identification, nephrology access, medication eligibility and transplant evaluation by race and socioeconomic position, rather than reporting equation deployment alone (Cusick 2025, PMID 40227684).

Validation results and implementation endpoints

Quantity Live-record result Interpretation
Development set, creatinine equation 8,254 participants; 31.5% Black Equation refit population (Inker 2021, PMID 34554658)
Development set, creatinine–cystatin C 5,352; 39.7% Black Combined-marker development
Validation set 4,050; 14.3% Black Compared with measured GFR
New creatinine equation bias, Black group −3.6 mL/min/1.73 m² (95% CI −5.5 to −1.8) Underestimation on median
New creatinine equation bias, non-Black group +3.9 (95% CI 3.4–4.4) Overestimation on median
Accuracy within 30% ≥85% for all equations P30 still permits clinically material individual error
Combined race-free equation More accurate, smaller group differences Supports wider cystatin C access
Implementation endpoint Referral, dosing, transplant evaluation, therapy uptake Must be measured after deployment (Delgado 2022, PMID 34563581)

What the switch actually did to populations

The page's "direction and magnitude depend on the population" caveat can now be replaced with measurements.

United States, demographically diverse system. Recomputing eGFR from serum creatinine measured 2016–2019 in 1,502,607 adults of the US Military Health System, the count of Black adults with CKD stages G3–G5 rose 58.1% (4,147 → 6,556; crude prevalence 1.47% → 2.32%) while the count of non-Black adults fell 30.4% (27,596 → 19,213; 2.26% → 1.58%). Among adults classified as G3–G5 by either equation, 45.8% of Black adults moved to a more advanced stage and 44.0% of non-Black adults to a less severe one, across thresholds that could change management (Oliver 2024, PMID 39100866).

Predominantly White European population. In 1.6 million Stockholm adults with creatinine measured 2007–2019, the 2021 equation raised eGFR by a median 3.9 (IQR 2.9–4.8) mL/min/1.73 m², more at older age and in men; 9.9% of the whole population and 36.2% of those with G3a–G5 were reclassified to a higher eGFR category. Reclassified individuals had lower risk of kidney failure with replacement therapy but higher risk of all-cause and cardiovascular death and major adverse cardiovascular events than non-reclassified people at the same eGFR — and both equations discriminated and calibrated equally within the Kidney Failure Risk Equation (Fu 2023, PMID 35689668). In a population with almost no Black participants, the reform is therefore not neutral: it shifts a third of stage-3–5 patients upward, changing who is counted as having CKD without changing prognostic performance.

A masked high-risk subgroup. Among 31,298 Black and 27,542 White people with HIV, the race-adjusted equation made Black participants appear at lower risk of progressing from eGFR stage 1 to 2 (HR 0.77, 95% CI 0.73–0.82) while showing a three-fold risk of progressing from stage 3 to 4/5 (HR 3.06, 2.60–3.62). The race-free equation reclassified 16% of Black participants into a more severe baseline stage; those reclassified had a higher prevalence of CKD risk factors, and under the race-free equation Black participants showed higher progression risk at every stage (Muiru 2023, PMID 36069064). The authors' framing is the sharpest available statement of the mechanism: the original equation systematically masked a high-risk subgroup rather than merely shifting a number.

The unintended-consequence literature

Lower reported eGFR opens some doors and closes others. In 459 self-identified Black patients who underwent nephrectomy at a tertiary centre (2009–2021), median CKD-EPI eGFR fell from 76 to 66 mL/min/1.73 m² without the race coefficient and median MDRD eGFR from 71 to 58; simulating common oncology trial eligibility floors, an additional 13–22% of these patients fell below 60, 6–12% below 45 and 2–3% below 30 mL/min, depending on the equation (Schmeusser 2023, PMID 36606692). Because Black patients are already under-represented in cancer trials, a reform intended to correct one inequity can widen another downstream — the same reported number that triggers earlier nephrology attention also triggers exclusion from drug access.

This is the concrete form of the audit requirement stated above: implementation should be evaluated on referral, drug eligibility, trial enrolment and transplant listing separately, because the sign of the effect differs between them.

Transplant waiting time: the one place the change was made retroactive

In 2023 the OPTN required US kidney transplant programmes to identify all Black candidates on their waiting lists and consider modifying accrued waiting time to undo disadvantage created by race-inclusive eGFR — a rare instance of a health system retrospectively compensating individuals for an algorithm (Pavlakis 2023, PMID 37488677). Implementation was uneven. Of 44,912 Black candidate listings between 6 January and 31 December 2023, 32% (14,419) received an eGFR-based waiting-time modification, with significant variation by candidate characteristics and by transplant centre; modification was more likely in candidates aged 65–69 (aOR 1.60, 95% CI 1.49–1.72) and ≥70 (aOR 1.52, 1.40–1.66) than 18–49, in women (aOR 1.09, 1.04–1.14) and in those listed pre-emptively (aOR 2.58, 2.46–2.72). Candidates who received modification had close to three-fold higher rates of deceased-donor transplantation (Schold 2025, PMID 40327843).

Two readings are available and the data do not choose between them: that the policy worked (modified candidates were transplanted far faster), or that centre-level variation in who was identified created a new inequity on top of the one being corrected. The three-fold transplant-rate difference is not a causal effect of the modification alone, since candidates eligible for modification differ systematically from those who were not.

Ancestry-informative biology has not gone away

Removing race from an equation does not remove genotype from pathophysiology. APOL1 high-risk genotypes carry large effects on non-diabetic kidney disease (see causes and aetiology) (Genovese 2010, PMID 20647424). The most consequential recent evidence concerns living donors: among 445 Black and 208 White US living kidney donors from 2000–2008 re-examined at home a median 18.5 years (IQR 16.9–20.5) after donation, 68 Black donors (15.3%) carried an APOL1 high-risk genotype, and those donors had higher risk of reaching eGFR below 45 mL/min/1.73 m² than Black donors without the genotype; 7.0% of all participants had eGFR below 45 (Hsu 2026, PMID 42329639).

The coherent position is therefore not "race matters" or "race does not matter" but that a social category was doing duty for a genetic variant it only loosely tracks — with the added asymmetry that APOL1 status is testable in an individual while race is not a biological measurement at all.

Children and young adults: the same question, a cleaner answer

The adult race debate was conducted on creatinine-based equations whose race term was empirical. In paediatric CKD, the same question was tested directly against iohexol-measured GFR. Among CKiD participants — 190 Black and 675 non-Black contributing 473 and 1,897 annual person-visits — self-reported Black race was associated with 12.8% higher measured GFR in models including serum creatinine, but 3.5% lower measured GFR after adjustment for cystatin C overall, and not significantly different above age 12. Adjustment for body size and socioeconomic factors did not change the results. Critically, the average of the creatinine- and cystatin C-based "U25" equations was unbiased across self-reported race groups (Ng 2022, PMID 34974031).

The finding isolates the mechanism cleanly. A race-associated difference appears in the creatinine relationship and largely reverses in the cystatin C relationship, which is what would be expected if the difference reflected creatinine generation — body composition and muscle mass — rather than filtration. And the practical resolution mirrors the adult one: a two-marker average removes the bias without needing a race term at all.

Decision and interpretation matrix

Dimension Question Guardrail
Diagnostic axis Cause + G category + A category Avoid treating eGFR as the diagnosis
Time axis Chronicity and trajectory Separate acute change from persistent disease
Risk axis Kidney failure + cardiovascular events + death Show competing events
Treatment axis Eligibility, absolute benefit, harm, burden Do not rank drugs by relative effect alone
Measurement axis Assay, equation, repeatability State what was actually measured
Equity axis Testing, referral, access, affordability Audit downstream care, not labels only
Patient axis Symptoms, function, life participation Include outcomes patients prioritize
Evidence axis RCT, cohort, model, guideline Do not collapse designs

Evidence ledger

This ledger makes the page’s evidentiary mix inspectable. It does not imply that every source answers every question.

PMID Record used Role and boundary
34554658 New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. (Inker 2021, PMID 34554658) Observational or conceptual evidence; association is not treatment effect.
34563581 A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease. (Delgado 2022, PMID 34563581) Guideline or commentary; recommendation evidence depends on its review.
40227684 Balancing Efficiency and Equity in Population-Wide CKD Screening. (Cusick 2025, PMID 40227684) Modelled projection; the estimate follows from the model inputs and assumptions, not from observed randomized follow-up.
37787795 Estimated GFR, Albuminuria, and Adverse Outcomes: individual-participant data meta-analysis. (CKD Prognosis Consortium 2023, PMID 37787795) Synthesis; heterogeneity and included-study definitions constrain transport.
38490803 KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. (KDIGO CKD Work Group 2024, PMID 38490803) Guideline or commentary; recommendation evidence depends on its review.
38519239 Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns. (Levin 2024, PMID 38519239) Guideline or commentary; recommendation evidence depends on its review.
32061315 Global, regional, and national burden of chronic kidney disease, 1990-2017. (GBD CKD Collaboration 2020, PMID 32061315) Modelled projection; the estimate follows from the model inputs and assumptions, not from observed randomized follow-up.
22038337 A population-based approach for the definition of chronic kidney disease: CKD Prognosis Consortium. (Cirillo 2012, PMID 22038337) Synthesis; heterogeneity and included-study definitions constrain transport.
23243116 Cohort profile: the chronic kidney disease prognosis consortium. (Matsushita 2013, PMID 23243116) Observational or conceptual evidence; association is not treatment effect.
30348535 Relationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities. (Inker 2019, PMID 30348535) Synthesis; heterogeneity and included-study definitions constrain transport.
26757465 Multinational assessment of equations predicting kidney failure. (Tangri 2016, PMID 26757465) Synthesis; heterogeneity and included-study definitions constrain transport.
36857500 Kidney Failure Risk Equation evaluation with novel inputs in 59 cohorts. (Grams 2023, PMID 36857500) Observational or conceptual evidence; association is not treatment effect.
26028594 eGFR and albuminuria for prediction of cardiovascular outcomes: individual-participant meta-analysis. (Matsushita 2015, PMID 26028594) Synthesis; heterogeneity and included-study definitions constrain transport.
32970396 Dapagliflozin in Patients with Chronic Kidney Disease. (Heerspink 2020, PMID 32970396) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
36331190 Empagliflozin in Patients with Chronic Kidney Disease. (EMPA-KIDNEY Collaborative Group 2023, PMID 36331190) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
30990260 Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. (Perkovic 2019, PMID 30990260) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
41205219 Chronic Kidney Disease Prevalence and Awareness Among US Adults. (Gong 2026, PMID 41205219) Observational or conceptual evidence; association is not treatment effect.
38213490 Cost-effectiveness of screening for chronic kidney disease: evidence and gaps. (van Mil 2024, PMID 38213490) Guideline or commentary; recommendation evidence depends on its review.
39137037 Screening for chronic kidney disease: change of perspective and novel developments. (van Mil 2024, PMID 39137037) Observational or conceptual evidence; association is not treatment effect.
38186904 Cost-effectiveness of screening for CKD in the general adult population: systematic review. (Yeo 2024, PMID 38186904) Synthesis; heterogeneity and included-study definitions constrain transport.
37403003 Chronic kidney disease of unknown aetiology: a global review. (Rao 2023, PMID 37403003) Observational or conceptual evidence; association is not treatment effect.
33116757 Mesoamerican Nephropathy: What We Know so Far. (Sanchez Polo 2020, PMID 33116757) Observational or conceptual evidence; association is not treatment effect.
18161745 Cellular and molecular mechanisms of fibrosis. (Wynn 2008, PMID 18161745) Observational or conceptual evidence; association is not treatment effect.
7246778 Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. (Hostetter 1981, PMID 7246778) Observational or conceptual evidence; association is not treatment effect.
24522492 Relative risks of CKD for mortality and end-stage renal disease across races are similar. (Wen 2014, PMID 24522492) Observational or conceptual evidence; association is not treatment effect.

What can and cannot be concluded

  • Risk associations do not by themselves establish that changing the marker changes risk.
  • A relative effect must be paired with baseline risk, follow-up and the exact endpoint.
  • Albuminuria, acute eGFR change, chronic eGFR slope and kidney failure are not interchangeable.
  • Subgroup consistency is not evidence that every subgroup had adequate power.
  • Guideline recommendations combine evidence with values, feasibility, cost and service capacity.
  • Older adults require competing-mortality and treatment-burden framing.
  • Dialysis and transplantation comparisons are vulnerable to eligibility and immortal-time bias.
  • Modelled lifetime benefit is not a randomized observed benefit.
  • A biochemical response without a patient-important outcome remains a surrogate result.
  • This page is research synthesis, not individualized medical advice.

Research-design checklist

  • Define CKD cause, G category, A category and chronicity at baseline.
  • Report the creatinine or cystatin C equation and laboratory calibration.
  • Prespecify acute and chronic eGFR slopes when haemodynamic effects are expected.
  • Keep sustained GFR decline, kidney failure and replacement therapy separable.
  • Report absolute event risks, follow-up and confidence intervals with relative effects.
  • Treat death as a competing event where it can preclude kidney failure.
  • Measure hyperkalaemia, acute kidney injury and treatment discontinuation consistently.
  • Include symptoms, function, life participation and treatment burden.
  • Describe background RAS, SGLT2, MRA and GLP-1 therapy explicitly.
  • Prespecify albuminuria and cause strata without over-reading underpowered interactions.
  • Record screening, prescribing, persistence and monitoring as separate implementation steps.
  • Report representation, access and affordability variables needed for equity analysis.

Open questions

  • Did race-free reporting change referral, drug eligibility and transplant evaluation, and for whom? The equation and the task-force recommendation are settled; the care-delivery outcome is not (Inker 2021, PMID 34554658) (Delgado 2022, PMID 34563581). → OQ-5
  • Has cystatin C access widened or narrowed disparities in practice? The recommendation assumes availability that is unevenly distributed (Delgado 2022, PMID 34563581).
  • Does a P30 of 85% leave enough individual error to matter at decision thresholds such as contrast, dosing and transplant listing? Accuracy was reported at population level (Inker 2021, PMID 34554658).

  • Which implementation metrics should systems be required to report after an equation change, rather than reporting deployment alone (Cusick 2025, PMID 40227684)?

  • Did race-free eGFR implementation improve or worsen net access? Reclassification moved 45.8% of Black adults with CKD to more advanced stages (Oliver 2024, PMID 39100866) and unmasked a high-risk subgroup (Muiru 2023, PMID 36069064), yet also pushed 13–22% more Black patients below common trial-eligibility floors (Schmeusser 2023, PMID 36606692). No study has measured the net effect on any patient-important outcome.

  • Why did only 32% of Black transplant candidates receive the mandated waiting-time modification, and does the centre-level variation constitute a new inequity (Schold 2025, PMID 40327843)?
  • Should APOL1 genotype now be reported where race once was, particularly in living-donor evaluation, where high-risk genotype carriers showed worse 18-year kidney function (Hsu 2026, PMID 42329639)?

  • In predominantly White populations the 2021 equation raises eGFR and reclassifies 36.2% of G3a–G5 patients upward with unchanged prognostic accuracy (Fu 2023, PMID 35689668) — is a definitional change that alters case counts without altering discrimination a clinical improvement or an accounting one?

  • If the race-associated difference appears in the creatinine relationship (+12.8% measured GFR) and reverses with cystatin C (−3.5%) in children (Ng 2022, PMID 34974031), is body composition a sufficient explanation of the adult race coefficient, and can it be measured directly instead?

References

  1. Inker et al. New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. N Engl J Med. 2021;385(19):1737-1749. PMID 34554658
  2. Delgado 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. Am J Kidney Dis. 2022;79(2):268-288.e1. PMID 34563581
  3. Cusick et al. Balancing Efficiency and Equity in Population-Wide CKD Screening. JAMA Netw Open. 2025;8(4):e254740. PMID 40227684
  4. CKD Prognosis Consortium et al. Estimated GFR, Albuminuria, and Adverse Outcomes: individual-participant data meta-analysis. JAMA. 2023;330(13):1266-1277. PMID 37787795
  5. KDIGO CKD Work Group et al. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4S):S117-S314. PMID 38490803
  6. Levin et al. Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns. Kidney Int. 2024;105(4):684-701. PMID 38519239
  7. GBD CKD Collaboration et al. Global, regional, and national burden of chronic kidney disease, 1990-2017. Lancet. 2020;395(10225):709-733. PMID 32061315
  8. Cirillo et al. A population-based approach for the definition of chronic kidney disease: CKD Prognosis Consortium. J Nephrol. 2012;25(1):7-12. PMID 22038337
  9. Matsushita et al. Cohort profile: the chronic kidney disease prognosis consortium. Int J Epidemiol. 2013;42(6):1660-1668. PMID 23243116
  10. Inker et al. Relationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities. Am J Kidney Dis. 2019;73(2):206-217. PMID 30348535
  11. Tangri et al. Multinational assessment of equations predicting kidney failure. JAMA. 2016;315(2):164-174. PMID 26757465
  12. Grams et al. Kidney Failure Risk Equation evaluation with novel inputs in 59 cohorts. J Am Soc Nephrol. 2023;34(3):482-494. PMID 36857500
  13. Matsushita et al. eGFR and albuminuria for prediction of cardiovascular outcomes: individual-participant meta-analysis. Lancet Diabetes Endocrinol. 2015;3(7):514-525. PMID 26028594
  14. Heerspink et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020;383(15):1436-1446. PMID 32970396
  15. EMPA-KIDNEY Collaborative Group et al. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023;388(2):117-127. PMID 36331190
  16. Perkovic et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019;380(24):2295-2306. PMID 30990260
  17. Gong et al. Chronic Kidney Disease Prevalence and Awareness Among US Adults. JAMA Cardiol. 2026;11(1):77-81. PMID 41205219
  18. van Mil et al. Cost-effectiveness of screening for chronic kidney disease: evidence and gaps. Clin Kidney J. 2024;17(1):sfad254. PMID 38213490
  19. van Mil et al. Screening for chronic kidney disease: change of perspective and novel developments. Curr Opin Nephrol Hypertens. 2024;33(6):583-592. PMID 39137037
  20. Yeo et al. Cost-effectiveness of screening for CKD in the general adult population: systematic review. Clin Kidney J. 2024;17(1):sfad137. PMID 38186904
  21. Rao et al. Chronic kidney disease of unknown aetiology: a global review. Trop Med Int Health. 2023;28(8):588-600. PMID 37403003
  22. Sanchez Polo et al. Mesoamerican Nephropathy: What We Know so Far. Int J Nephrol Renovasc Dis. 2020;13:261-272. PMID 33116757
  23. Wynn et al. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008;214(2):199-210. PMID 18161745
  24. Hostetter et al. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am J Physiol. 1981;241(1):F85-F93. PMID 7246778
  25. Wen et al. Relative risks of CKD for mortality and end-stage renal disease across races are similar. Kidney Int. 2014;86(4):819-827. PMID 24522492
  26. Oliver JD, et al. Impact of Race-Free Glomerular Filtration Rate Estimations on CKD Prevalence in the US Military Health System: A Retrospective Cohort Study. Kidney Med. 2024;6(8):100861. PMID 39100866
  27. Fu EL, et al. Removing race from the CKD-EPI equation and its impact on prognosis in a predominantly White European population. Nephrol Dial Transplant. 2023;38(1):119-128. PMID 35689668
  28. Muiru AN, et al. Effect of Adopting the New Race-Free 2021 CKD-EPI eGFR Creatinine Equation on Racial Differences in Kidney Disease Progression Among People With HIV: An Observational Study. Clin Infect Dis. 2023;76(3):461-468. PMID 36069064
  29. Schmeusser BN, et al. Race-free renal function estimation equations and potential impact on Black patients: Implications for cancer clinical trial enrollment. Cancer. 2023;129(6):920-924. PMID 36606692
  30. Pavlakis M, et al. A Restorative Justice Project in Kidney Allocation-The Wait Time Modification for Black and African American Candidates Affected by the Race-Based eGFR Equation. J Am Soc Nephrol. 2023;34(10):1618-1620. PMID 37488677
  31. Schold JD, et al. Variation of eGFR Wait Time Modifications for Black Kidney Transplant Candidates in the United States. J Am Soc Nephrol. 2025;36(10):2019-2029. PMID 40327843
  32. Genovese G, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science. 2010;329(5993):841-845. PMID 20647424
  33. Hsu CY, et al. Apolipoprotein L1 Gene Genotype and Kidney Outcomes After Living Kidney Donation. JAMA Intern Med. 2026;186(8):943-950. PMID 42329639
  34. Ng DK, et al. Self-reported Race, Serum Creatinine, Cystatin C, and GFR in Children and Young Adults With Pediatric Kidney Diseases: A Report From the Chronic Kidney Disease in Children (CKiD) Study. Am J Kidney Dis. 2022;80(2):174-185.e1. PMID 34974031