Glomerular Filtration Rate.pptx

Review of Evidence for
Race in eGFR and its
Implication
Beka Aberra MD
Renal Fellow
April 29, 2022

OUTLINE
• Introduction
• Evidence for Equation Development
• Evidence for Race Correction
• Evidence for Counterarguments
• NKF-ASN Task Force Recommendation
• The African Context Review
• Take Home Message
• References

INTRODUCTION
• Clinical assessment of kidney function is central to the practice of
medicine.
• GFR is widely accepted as the best index of kidney function in health and
disease, and accurate values are required for optimal decision making.
• Estimated GFR based on serum creatinine is now widely reported by
clinical laboratories, and is sufficient for clinical decision making.
• If GFR estimates are likely inaccurate or if decisions based on inaccurate
estimates may have adverse consequences, a measured GFR is an
important confirmatory test.
L. A. Stevens and A. S. Levey, “Measured GFR as a Confirmatory Test for Estimated GFR,”
Journal of the American Society of Nephrology 20, no. 11 (November 1, 2009): 2305–13.

https://robbwolf.com/2011/06/16/clearing-up-kidney-confusion-part-deux/
Glomerular Filtration Rate (GFR)
• How fast the kidneys are
filtering the blood, in
milliliters/minute.
• Glomerular filtration rate (GFR) is generally
accepted as the best overall index of kidney
function.
• GFR ~ 120 ml/min Declines naturally with age
after ~40 (4-10ml/min/decade)
• KDIGO refers to a GFR <60 ml/min/1.73 m2 as
Decreased GFR and to a GFR <15ml/min/1.73
m2 as kidney failure.

Glomerular Filtration Rate
The sum of Filtered Load (GFR X P),
Tubular Secretion (TS), and
Tubular Reabsorption(TR).
Generation (G)
Extra renal elimination (E)
Generation (G)
Urinary excretion (UV)
The Plasma Level (P) of an
endogenous filtration marker
NON GFR
Determinants
of SCr/SCys …
MARKERS
EXOGENOUS
• Inulin
• 51Cr-EDTA
• 99mTc-DTPA
• 125I-Iothalamate
• Iohexol
ENDOGENOUS
• Serum creatinine
• Urea
• Cystatin-C
• b2m
• bTp
Ideal Marker (Gold standard)
Exogenous
Freely filtered at glomerulus
No tubular secretion or
reabsorption
No tubular metabolism
However…expensive, difficult,
invasive, time-consuming

Levey, A.S.,
Coresh, J.,
Tighiouart, H. et
al. Measured
and estimated
glomerular
filtration rate:
current status
and future
directions. Nat
Rev Nephrol 16,
51–64 (2020).

• Can be calculated with 24 hour urine and a blood draw
CrCl = UCr (mg/dl) x Uvolume (ml)
(SCr (mg/dl)) (1440 min)
• The Cr clearance exceeds the true GFR by ~10-20% or more since part of the
urinary Cr is derived from tubular secretion.
• Using Cr clearance to estimate GFR is limited by errors in urine collection and
variation in the degree of Cr secretion.
The main difference between GFR and CRCL is that GFR is the flow rate
of filtered fluid through the kidney whereas CrCl is the volume of
blood plasma cleared of creatinine per unit time
Creatinine Clearance

10
Estimation of GFR
1. Cockcroft-Gault Equation
(mL/min)
For women Multiply by 0.85
2. MDRD study equation
(mL/min/1.73 m2)
GFR = 186.3 x (SCr)−𝟏.𝟏𝟓𝟒
x (Age) −𝟎.𝟐𝟎𝟑
Multiply by 0.742 for women
Multiply by 1.21 for African ancestry
3. CKD-EPI equation GFR = 141 × min( SCr
κ )α
× max ( SCr
κ )−𝟏.𝟐𝟎𝟗× 0.993𝒂𝒈𝒆
Multiply by 1.018 for women
Multiply by 1.159 for African ancestry
κ is 0.7 for females and 0.9 for males, α is –0.329 for females and –0.411 for males, min
indicates the minimum of SCr/κ or 1, & max indicates the maximum of SCr/κ or 1
(140 − age) x LBW [kg]
Cr [mg/dL] x 72
CCr =

Key eGFR Milestones
1970 1980 1990 2000 2010 2020
1988-98: African American disparities in waitlisting & nephrology
referral documented (Eggers HCFR, Kinchen Ann Int Med)
1999: MDRD eGFR equation (Scr, age, sex, self-reported race
1.21) inclusion of women and Blacks (Levey Ann Int Med)
2007: 50% penetration of eGFR reporting (MDRD) in U.S.
laboratories (CAP Survey)
2009: CKD-EPI equation (Scr, age, sex, race 1.16) inclusion of women,
Blacks (few Asian and Hispanics) (Levey Ann Int Med)
2012: CKD EPI combined equation (Scr, Scys, age, sex, race 1.08)
(Inker NEJM)
2013: 90% penetration of eGFR reporting (MDRD>66%) in U.S.
laboratories (CAP Survey); Standardized assessment of kidney
function & equations incorporated into guidelines (KDIGO )
1976 Cockcroft-Gault equation developed in 249 white men & extrapolated
1982: African American disparities in ESRD documented (Rostrand NEJM)
1998 Mean creatinine values higher in U.S. non-Hispanic blacks (Jones AJKD)
The FACTS: Key eGFR Milestones

Serum creatinine in U.S. Population by Race,
Age and Sex: NHANES III 1988-94
0.6
0.7
0.8
0.9
1
1.1
1.2
1.3
1.4
1.5
1.6
12-19 20-39 40-59 60+
mg/dl
Age
Non Hispanic Black Men
Non Hispanic White Men
Non Hispanic Black Women
Non Hispanic White Women
Jones CA, McQuillan GM, Kusek JW, Eberhardt MS, Herman WH, Coresh J, Salive M, Jones CP, Agodoa LY. Serum creatinine
levels in the US population: third National Health and Nutrition Examination Survey. Am J Kidney Dis. 1998 Dec;32(6):992-9.

Key eGFR Milestones
1970 1980 1990 2000 2010 2020
1988-98: African American disparities in waitlisting & nephrology
referral documented (Eggers HCFR, Kinchen Ann Int Med)
1999: MDRD eGFR equation (Scr, age, sex, self-reported race 1.21)
inclusion of women and Blacks (Levey Ann Int Med)
2007: 50% penetration of eGFR reporting (MDRD) in U.S.
laboratories (CAP Survey)
2009: CKD-EPI equation (Scr, age, sex, race 1.16) inclusion of women,
Blacks (few Asian and Hispanics) (Levey Ann Int Med)
2012: CKD EPI combined equation (Scr, Scys, age, sex, race 1.08)
(Inker NEJM)
2013: 90% penetration of eGFR reporting (MDRD>66%) in U.S.
laboratories (CAP Survey); Standardized assessment of kidney
function & equations incorporated into guidelines (KDIGO )
1976 Cockcroft-Gault equation developed in 249 white men & extrapolated
1982: African American disparities in ESRD documented (Rostrand NEJM)
The FACTS: Key eGFR Milestones

• MDRD (the Modification of Diet in Renal Disease study)
• More precise than Cockcroft Gault equation
• Less cumbersome than 24-hour urine creatinine clearance
• Participants: Black (n=197) & White (n=1304)
• Regression model
• multiple biologic variables and self-reported Black race, p<0.001
• Age, gender, self-reported Black race
• Did not account differences in baseline characteristics
• “if African American” ✕ 1.21
• eGFR ≈ gold standard GFR
Levey et al. Ann Intern Med. 1999.

Estimation of GFR from Creatinine
• Modification of Diet in Renal
Disease (MDRD) study
• 1.75 x SCr-1.154 x Age-0.203 x [0.742 if
female] x [1.21 if African American]
SCr = serum creatinine in mg/dL
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): 461–70.
Levey AS, Coresh J, Greene T et al. Chronic Kidney Disease Epidemiology Collaboration. Using standardized serum creatinine values in the
modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006 Aug 15;145(4):247-54
Racist or
Evidenced-Based,
Precision
Medicine?

Higher Creatinine in Black vs White adults at same
Measured GFR
Levey AS, Bosch JP, Lewis JB et al. A More Accurate Method To Estimate GFR from Serum Creatinine: A
New Prediction Equation. Ann Intern Med 1999
Lewis J, Agodoa L, Cheek D, et al. Comparison of Renal Function Measurements in African Americans
With Hypertensive Nephrosclerosis and Formulas to Estimate GFR. AJKD 2001
• Results in NIDDK-sponsored African American Study of Kidney Disease (AASK) were
consistent with MDRD Study despite differences in characteristics such as mean level of GFR,
BMI, albumin, and urea.
. White adults - - - o Black adults --
Race self-reported

“…on average black persons have
higher muscle mass than white
persons.”
• Cohn et al. 1997
• 47 Black and 67 White adults
• “Blacks had higher total-body calcium and potassium than the…White
population.”
• Worrall et al. 1990
• 30 Black and 30 White adults
• “Racial variation in creatine kinase was independent of lean body
mass.”
• Harsha et al. 1978
• 99 Black and 143 White children in Louisiana
• “Black children were found to have less body fat than White children.”
Grubbs V. Precision in GFR Reporting: Let’s Stop Playing the Race Card. Clin J Am Soc Nephrol. May 2020.

• CKD-EPI (Chronic Kidney Disease Epidemiology
Collaboration)
• More precise at higher GFR than MDRD
• Equation development from 8,254 participants in 10 studies
• More diverse: 5% Hispanic and Asian
• Black versus Non Black [Others] from start
• “if African American” ✕ 1.16
Levey et al. Ann Intern Med. 2009.

CKD EPI Equation Derivation
• Equations derived empirically using pooled data from studies
measuring creatinine and GFR
• 8254 participants in 10 studies (equation development data set)
• 3896 participants in 16 studies (validation data set)
• Blacks were 30.5% (2601) of derivation and 12% (451) of
validation; 1807 from African American Study of Kidney Disease
• Race/ethnicity was self-reported (not provider assigned)
• In the development data set coefficients were:
• Whites(n=5216) 1.0 (reference standard)
• Hispanics and Native Americans (n=353) 1.01 n.s.
• Asians (n=100) 1.05
• African Americans (n=2585) 1.16
• However, eGFR equations do not perform well in some
populations from Africa and Asia
Levey AS et al A new equation to estimate GFR. Annals of Internal Medicine 2009; 150: 604-612
Stevens LA et al. Evaluation of the CKD Epidemiology Collaboration equation for estimating the GFR in
multiple ethnicities. Kidney Int. 2011;79(5):555-62.
Normalized to White
as reference standard

Timeline of Key eGFR Milestones
1970 1980 1990 2000 2010 2020
2017-2019: Calls for race removal
from eGFR reporting
2020: More calls - > institutions
remove race from eGFR reporting
2021: Task Force Report
2020: NKF-ASN Task Force
1976 Cockcroft-Gault equation developed in 249 white men
1988-98: African American waitlist & referral disparities documented
1999: MDRD eGFR equation inclusion of women and Blacks
2007: 50% penetration of eGFR reporting in U.S. labs
2009: CKD-EPI equation - women, Blacks, few Asians & Hispanics
2012: CKD EPI combined equation, diverse
2013: 90% eGFR reporting; KDIGO guidelines
Key Historical Points
Disparities existed before race equations
Equation development followed up on health statistics
data and evolved to increase diversity & to reflect non-
GFR determinants of serum creatinine
Race removed in reporting, not in calculations

Timeline of Key eGFR Milestones
• 1976 Cockcroft-Gault equation developed in 249 white men
• 1999: MDRD eGFR equation (Scr, age, sex, race 1.21) published with inclusion of women
and Blacks (Levey 1999)
• 2007: 50% penetration of eGFR reporting (MDRD) in U.S. clinical laboratories (CAP
Survey)
• 2009: CKD-EPI equation (Scr, age, sex, race 1.16) published with inclusion of women,
Blacks (few Asian and Hispanics) (Levey 2009)
• 2012: CKD EPI combined equation (Scr, Scys, age, sex, race 1.08) (Inker 2012)
• 2013: 90% penetration of eGFR reporting (MDRD>66%) in U.S. clinical laboratories (CAP
Survey); standardized assessment of kidney function and equations incorporated into
clinical practice guidelines (KDIGO 2013 )
• 2017: First call for race removal from eGFR reporting
• 2020: More calls - half dozen institutions remove race from eGFR reporting >> NKF-ASN
Task Force Creation, 2021 Interim report.

Why it matters
• Epidemiology
• Black patients progress to end-stage kidney disease nearly 3 ✕ faster than
White patients
• Black patients are less likely to receive kidney transplants than White patients
• Racism, not race, is the risk factor
• Clinical implications
• Referral to nephrology care
• Referral for kidney transplant evaluation
• Medication
o Dosing
o Appropriateness: Glucophage, sodium-glucose co-transporter-2 (SGLT2) inhibitors, HIV
medications
• NOT JUST FOR BLACK PEOPLE!
USRDS 2020 Annual Data Report.
Kulkarni et al. JAMA Surg. 2019.

Normal
Chronic Kidney
Disease
(CKD)
End Stage
Kidney Disease
(ESKD)
~26 million ~500,000
Dialysis
Transplant
Forgo dialysis
Expected remaining
life for 64-year-old
6 years
weeks to 2-3 years
15 years
USRDS 2020 Annual Data Report
Start dialysis 5-8
Transplant wait list
Refer CKD to nephrology
Medication threshold
https://www.niddk.nih.gov/health-information/professionals/advanced-search/explain-kidney-test-results
CKD, chronic kidney disease
Kidney donor eligibility

42.1
34.1 30
0
20
40
60
White, not
Hisp/Latino
Black, not
Hisp/Latino
Hispanic or
Latino
Proportion
CKD care from nephrologist > 12 mos.
before start of kidney replacement Tx
- 2018
16 14.6 12.2
0
10
20
White, not
Hisp/Latino
Hispanic or
Latino
Black, not
Hisp/Latino
Proportion
Dialysis pts waitlisted and/or receiving a
kidney (deceased donor) TX < 1 yr of
ESKF start (<70 years of age) - 2017
United States Renal
Data System. 2020
USRDS Annual Data
Report: Epidemiology
of kidney disease in
the United States.
NIH, NIDDK 2020.

For a 55 Yrs /F SCr of 2.8 mg/dL, a white woman would be referred for a
transplant, a black woman would not.
For an 80 Yrs/F SCr of 1 mg/dl, a White woman-CKD not Black woman.

Black patients must have kidney function lower than the lines to be eligible for kidney transplant waiting
list or nephrology referral.
Kidney Tx Waitlist Eligibility
Nephrology Referral Guideline
Is Use of Race in Kidney Function Estimation Race-Based Medicine
and Does it Restrict Access to Care?
534 African American
adults in the Chronic
Renal Insufficiency
Cohort. eGFR calculated
using CKD-EPI equation
Eneanya ND, Yang W, Reese PP. Reconsidering the Consequences of Using Race to Estimate Kidney Function.
JAMA. 2019 Jul 9;322(2):113-114.

Ahmed et al. J Gen Intern Med. 2020.
Clinical Impact of “race correction”
• Single-center
CKD Registry
• N=56,845
• N=2,225 (3.9%)
African
Americans
• 0 of 64 referred
for transplant
evaluation

Levey et al. Clin J Am Soc Nephrol. 2020
The Counterargument

Expected Impact on Black Patients if
Implemented Across the U.S.
Diao JA, Wu GJ, Taylor HA, Tucker JK, Powe NR, Kohane IS, Manrai AK. Clinical Implications of Removing Race From
Estimates of Kidney Function. JAMA. 2020 PMID: 33263721
Benefits?
Harms?

No. of Black Patients ineligible or recommended to receive anti-
cancer drug renal dose adjustment increased by:
• 72% for cisplatin
• 120% for pemetrexed
• 67% for bendamustine
• 150% for capecitabine
• 150% for etoposide
• 67% for topotecan
• 61% for fludarabine
• 163% for bleomycin
Casal MA, Ivy SP, Beumer JH, Nolin TD. Effect of removing race from GFR-
estimating equations on anticancer drug dosing and eligibility: a retrospective
analysis of NCI phase 1 clinical trial participants. Lancet Oncol. 2021 ;22(9):1333-
1340.
*Essien UR, Dusetzina SB, Gellad WF. A Policy Prescription for Reducing Health Disparities-Achieving Pharmacoequity. JAMA. 2021
Pharmacoequity*: eGFR with vs without
race term dropped

Clinical Trial Diversity
eGFR with vs without race term dropped
• Where trials exclude patients with lower eGFR, recalculating
eGFR without vs with the race-specific coefficient may
decrease the proportion of Black participants in trials.
• CREDENCE: RCT of canagliflozin (sodium–glucose
cotransporter 2 inhibitor) vs placebo in T2DM & CKD
• eGFR recalculation with race coefficient dropped had small but
potentially important effects on event rates and the relative
proportion of Black participants, without substantially changing
efficacy estimates.
Could compromise longstanding efforts to diversify,
populations enrolled in clinical trials.
Charytan D, Yu J, Jardine M, Cannon C, Agarwal R, Bakris G, Greene T, Levin A, Pollock C, Powe N, Arnott C, Mahaffey K. Potential
Effects of Elimination of the Black Race Coefficient in eGFR Calculations in the CREDENCE Trial. Clin J Am Soc Nephrol. 2022 Jan
21:CJN.08980621. doi: 10.2215/CJN.08980621. PMID: 35063969.

General Approaches to Mitigate Use of Race in
Estimating or Reporting GFR in Routine Clinical
Practice
• Return to the Past: Scr or CG
• Measure GFR: (e.g. iothalamate)
• Substitute Phenotypes - e.g. low vs high muscle mass
• Blended Race – recalculate with specified % B vs NB
• Raceless Markers- e.g. cystatin C
• Dominant Race Standard-drop race coeff & norm to
White
Scr – serum creatinine alone
CG – Cockcroft-Gault equation
(Scr, weight, age, sex)
Powe NR. Black Kidney Function Matters: Use or Misuse of Race.
JAMA 2020; 324(8): 737-738. PMID: 32761164.

Racial Phenotyping
Approach Advantages or Challenges
Substitute “low muscle
mass” and “high muscle
mass’ for “non black” and
“black”
Removes race in reporting. Recognizes
participation of blacks in derivation studies.
Assumes race is a proxy for muscle mass,
(stereotyping all blacks as having high
muscle mass), high muscle mass = higher
creatinine, and we can measure muscle
mass in clinical practice. Likely less
accurate for blacks.

Blended Race Standard
Develop new equation from
CKD-EPI data using average
of ethnicity coefficients (e.g.
32% of black CKD EPI
participants, 13% of blacks
in U.S. or % of blacks at a
health care institution)
Removes race in reporting.
Recognizes participation of
blacks in derivation studies.
Requires agreement on racial
composition of sample. Likely
less performance for both
Black and non Black persons
but may be equitable and
acceptable.
JAMA 2020; 324(8): 737-738. PMID: 32761164.

Newer Raceless Markers
Using non-creatinine
filtration markers for
which race does not
add greater precision
(e.g cystatin C)
Does not incorporate race in
estimation or reporting.
Standardization improving,
higher cost, not widely available
now,. Uncertain performance in
very ill patients
Use when decision making could affect patient health
JAMA 2020; 324(8): 737-738. PMID: 32761164.

Dominant Race Standard
(Normalization to White)
Discard race
coefficient from
equations and report
the “non-Black”
estimate
Removes race in reporting but not
computation. Discriminatory
because it ignores creatinine data
on Black persons from studies
included in equation derivation?
Likely less accurate for blacks.
JAMA 2020; 324(8): 737-738. PMID: 32761164.

Dominant Race Standard
• CKD Epidemiology (CKD EPI) Collaboration
– 141 x min (SCr/k,1)a x max(SCr/k,1)-1.209 X 0.993Age x
[1.018 if female]x [1.159 if African American] [1] Like Whites
SCr = serum creatinine in mg/dL
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J; CKD-EPI. A new equation to estimate
glomerular filtration rate. Ann Intern Med 2009 May 5;150(9):604-12.
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (March 1999). 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 130 (6): 461–70.
k = 0.7 for females and 0.9 for males
a = 0.329 for females and -0.411 for males
min indicates the minimum of SCr/k or 1
max indicates the maximum of SCr/k or 1.
• Discounts creatinine data contributed by 31% of Blacks in
the 26 pooled studies that included a gold standard of
directly measured GFR
• Derivation n=8254: 2601 Blacks (31%), 1807 from African
American Study of Kidney Disease
• Validation n=3896: 451 Blacks (12%)
• Normalizes to Whites creatinine as reference standard
x [1.159 if African
American]

48
A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on
Reassessing the Inclusion of Race in Diagnosing Kidney Disease
Cynthia Delgado, MD, Mukta Baweja, MD, Deidra C. Crews, MD, ScM, Nwamaka D. Eneanya, MD, MPH,
Crystal A. Gadegbeku, MD, Lesley A. Inker, MD, MS, MallikaL. Mendu, MD, MBA, W. Greg Miller, PhD,
Marva M. Moxey-Mims, MD, Glenda V.Roberts, BSc, Wendy L. St. Peter, PharmD, Curtis Warfield, MS, Neil
R. Powe, MD,MPH, MBA
New Creatinine- and Cystatin C–Based Equations to Estimate
GFR without Race
L.A. Inker, N.D. Eneanya, J. Coresh, H. Tighiouart, D. Wang, Y. Sang, D.C. Crews,
A. Doria, M.M. Estrella, M. Froissart, M.E. Grams, T. Greene, A. Grubb,
V. Gudnason, O.M. Gutierrez, R. Kalil, A.B. Karger, M. Mauer, G. Navis,
R.G. Nelson, E.D. Poggio, R. Rodby, P. Rossing, A.D. Rule, E. Selvin, J.C. Seegmiller,
M.G. Shlipak, V.E. Torres, W. Yang, S.H. Ballew, S.J. Couture, N.R. Powe,
and A.S. Levey, for the Chronic Kidney Disease Epidemiology Collaboration*
Race, Genetic Ancestry, and Estimating Kidney Function in
CKD
C. Hsu, W. Yang, R.V. Parikh, A.H. Anderson, T.K. Chen, D.L. Cohen, J. He, M.J. Mohanty, J.P. Lash, K.T. Mills, A.N.
Muiru, A. Parsa, M.R. Saunders, T. Shafi, R.R. Townsend, S.S. Waikar, J. Wang, M. Wolf, T.C. Tan, H.I. Feldman, and
A.S. Go, for the CRIC Study Investigators*
September 23, 2021
Joint Publication online in AJKD and JASN
PMID: 34563581 AJKD and 34556489 JASN
Also new pivotal research published online in NEJM
September 23, 2021

NKF- ASN Task Force Members
Lesley Inker MD
Mallika L. Mendu MD
W. Greg Miller PhD
Marva Moxey-Mims MD
Glenda V. Roberts BSc
Wendy L. St. Peter PharmD
Curtis Warfield
Crystal A. Gadegbeku MD
Nwamaka D. Eneanya MD Deidra C. Crews MD
Nilka Rios Burrows MPH, MT
Mukta Baweja MD
Neil R. Powe MD, Cochair
Cynthia Delgado MD, Cochair
Broad expertise, including (but not limited to) health and health care disparities, epidemiology and health services research,
genetic ancestry, clinical chemistry, patient safety and performance improvement, pharmacology, social sciences.

NKF-ASN Task Force Process
• Sought wide range of evidence & views with diverse representation
• 40 sessions: 97 people from 21 U.S. states and 7 countries
• 3 community forums: 53 trainees, providers or patients or written testimony
(450 people from 18 states and 3 countries)
• Made call for new science in open invitation
• Sessions moderated by different task force members
• Statements of Evidence and Value n=30, 97 references: cornerstone in forging a
path forward
• Equity and disparities
• Race and racism
• GFR measurement, estimation, and equation performance
• Laboratory standardization
• Patient perspectives
• Described in Interim Report
Delgado C, Baweja M, Burrows NR, Crews DC, Eneanya ND, Gadegbeku CA, Inker LA, Mendu ML, Miller WG, Moxey-Mims MM, Roberts GV,
St Peter WL, Warfield C, Powe NR. Reassessing the Inclusion of Race in Diagnosing Kidney Diseases: An Interim Report from the NKF-ASN
Task Force. J Am Soc Nephrol. 2021 Jun 1;32(6):1305-1317 and Am J Kidney Dis. Jul;78(1):103-115.

Joint Publication online
Apr 9, 2021 PMID:
33837122 and33845065
Interim Report of NKF-ASN Task Force

Estimating Equations Options:
26 Approaches considered in these general categories
Creatinine Used as Biomarker
• Estimation and reporting with creatinine
and race using existing equations [1]
• Estimation with creatinine and race using
existing equations but reporting without
specification of race [5]
• Estimation with creatinine that do not
include race [4]
• Equations to be developed to estimate
GFR with creatinine that do not include
race [2]
Noncreatinine Biomarker Used
• Estimation with cystatin C, creatinine, and race
using existing equations [1]
• Estimation with cystatin, creatinine, and race
using existing equations but reporting without
specification of race [5]
• Estimation with cystatin C only [3]
• Equations to be developed to estimate GFR
with creatinine and cystatin C that do not
include race [1]
• Estimation with creatinine and cystatin that
does not include race [1]
• Estimations with new filtration markers in
combination with creatinine or cystatin C that
do not include race [2]

• TF members divided into attribute-defined subgroups, based on expertise, to
examine alignment of each desired attribute with each of the 26 eGFR approaches.
• Five alternative approaches selected after extensive discussion
• Task Force did review information on all 26 approaches for completeness.
• Final recommendations reviewed by leaders in NKF and ASN with expertise in
health equity, health care justice, quality of patient care, research, policy and
advocacy.
• Process took 10 months: September 2020-June 2021.
• Report then written over 1 month and submitted for peer-review.
NKF-ASN Task Force Process

54
Bias (population statistic)
Median (mGFR-eGFR)
Individual statistics:
Accuracy, P30
% estimates within
30% of mGFR
Correct classification
% estimates in the same
GFR category for CKD staging
ASR =Age-Sex-Race
Performance of Equations
Inker LA, Eneanya ND, Coresh J, et al Chronic Kidney Disease Epidemiology Collaboration.
New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. N Engl J
Med. 2021 Sep 23. PMID: 34554658.

Task Force Recommendation 1
1. Immediate implementation of 2021 CKD-EPI creatinine equation
refit without the race variable in U.S. labs
Rationale:
• Does not include race in the calculation and reporting
• Includes diversity in its development
• Is immediately available to all labs in the U.S.
• Has acceptable performance characteristics and has potential consequences
that do not disproportionately affect any one group of individuals.
eGFR = 142 X min(Scr/k,1)α X max(Scr/k,1)-1.200 0.9938age X 1.012 [if female]
where Scr is standardized serum creatinine in mg/dL; κ = 0.7 mg/dL for females or 0.9 mg/dL
for males; α is -0.241 for females and -0.302 for males; min = indicates minimum of SCr/κ or 1;
max indicates maximum of SCr/κ or 1; and age is in years. Inker et al N Engl J Med. 2021 Sep 23

56
NB – drops the black coefficient
(assigns non-Black eGFR to Black participants) Results in all
the bias 7.1 ml/min too low in the Black participants
eGFRcr: Widely
Used and Useful
BUT
– creatinine is
biased by “race”
Performance of eGFRcr Equations
Inker LA, Eneanya ND, Coresh J, et al Chronic Kidney Disease
Epidemiology Collaboration. New Creatinine- and Cystatin C-
Based Equations to Estimate GFR without Race. N Engl J Med.
2021 Sep 23. PMID: 34554658.
AS – new CKD-EPI
2021 eGFRcr
From regression that is
race blind
Splits the bias evenly
across groups
[One estimate for all
people]

Task Force Recommendations 2 & 3
2. National efforts to facilitate increased, routine, and timely use
of cystatin C, especially for confirmation of eGFR.
• If ongoing evidence supports acceptable performance, the CKD-
EPI eGFR-cystatin C (eGFRcys) and eGFR creatinine-cystatin C
(eGFRcr-cys) refit without the race variables should be
adopted to provide another first-line test, in addition to
confirmatory testing.
3. Investment in science is needed.
• GFR estimation with new endogenous filtration markers.
• Interventions to eliminate racial and ethnic disparities

58
eGFRcys: One race unbiased marker
Performance of eGFRcys Equation
Cystatin has no bias by race but less accurate than 2 filtration markers
Inker LA, Eneanya ND, Coresh J, et al Chronic Kidney Disease
Epidemiology Collaboration. New Creatinine- and Cystatin C-Based
Equations to Estimate GFR without Race. N Engl J Med. 2021 Sep 23.
PMID: 34554658.

59
eGFRcr-cys: more accurate (P30~90%),
smaller bias by race [likely more robust]
Performance of eGFRcr-cys Equations
2 filtration markers  more accuracy and less sensitivity to race
Inker LA, Eneanya ND, Coresh J, et al Chronic Kidney Disease Epidemiology Collaboration.
New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. N Engl J Med.
2021 Sep 23. PMID: 34554658.

The African Context
•Congo
•Cote D’Ivoire
•South Africa
•Ghana
•Ethiopia
• Bukabau et al. PLOS1.2018.
• Bukabau et al. Kidney International. 2019.
• Van Deventer et al. Clin Chem. 2008.
• Eastwood et al. Nephrol Dial Transplant 2010.
• Levey and Inker Kidney International 2019…..
 Race Multiplier [for Non GFR determinants of Scr] for both MDRD/CKD-
EPI is NOT Valid in African Studies.

Variables Frequency(n) Percent (%)
Age (years) <39 27 27
40-59 41 41
>60 32 32
Total 100 100
Sex distribution Male 43 43
Female 57 57
Total 100 100
Variables Overall (n=100) Male (n=43) Female(n=57) P value
Age(years) 50.3(16.9) 56.2 (16.6) 45.9 (15.8) 0.002
Weight(kg) 63.4(13.1) 64.4 (11.6) 62.7 (14.2) 0.49
Height(cm) 162.4(7.4) 167.6 (5.8) 158.5 (6) <0.0001
BMI (kg/m2) 24.02(4.70) 22.9 (3.6) 24.9 (5.2) 0.027
Serum creatinine(mg/dl) 1.14(1.4) 2.05 (1.6) 1.4 (1.2) 0.029
Creatinine clearance (ml/min/1.73m2) 56.9(36.9) 49.4 (32.5) 62.7 (39.2) 0.071
MDRD(ml/min/1.73m2) 81.1(49) 67.7 (39.1) 91.3 (53.5) 0.013
MDRD without race
factor(ml/min/1.73m2)
66.9(40.5) 55.9 (32.3) 75.3 (44.2) 0.013
CKD-EPI(ml/min/1.73m2) 75.4(42.5) 62 (34.4) 85.5 (45.5) 0.004
CKD-EPI without race
factor(ml/min/1.73m2)
65.4(36.9) 53.6 (29.8) 74.2 (39.5) 0.004
Cockcroft-gault(ml/min/1.73m2) 68.3(42) 51.3 (29) 81.2 (45.8) <0.0001

Results:
Mean GFR by CrCl was 56.9 ml/min/1.73 m2.
 Mean MDRD-4 eGFR was 81.1 ml/min/1.73 m2 (difference vs. CrCl,-24.22: 95%CI: -29.1 – -19.3); when
the factor for black race was omitted, the value (difference vs CrCl,-10.03) mean 66.9 ml/min/1.73m2)
was closer to CrCl.
 Mean CKD-EPI eGFR was 75.4 ml/min/1.73m2 (difference vs. CrCl,-18.49: 95%CI: -22.4 – -14.5) , and
65.4 ml/min/1.73 m2(difference vs. CrCl,-8.49: 95%CI: -12.02 – -4.96); when the factor for race was
omitted.
 Mean Cockcroft-gault eGFR was 68.3 ml/min/1.73 m2 (difference vs. CrCl,-11.4: 95%CI: -15.59– -7.25).
The percentage of individuals identified with CKD stages 3–5 (GFR<60 ml/min/1.73 m2) depended on the
method used: CrCl 58%;
 MDRD 41% (46% without factor for black race;
 CKD-EPI 41% (45% without factor for black race), and
 Cockcroft–Gault 48%.

• Claim: Using race in clinical algorithms such as those for eGFR
institutionalizes racism and its incorporation causes disparities
RACE
Should race be part of patient care and clinical
decision making?

• Elimination of race is a worthy aspiration, but
consequences are far reaching.
• Making changes is not a trivial task- We have to seek
“Correct Estimation” not “Under or Over Estimation”
• Newer race less estimation markers may offer a path
forward, but need to be scaled up, widely adopted and
monitored.
Take Home Message
# NO-MORE RACE BASED MEDICINE AND
# MORE EVIDENCE BASED MEDICINE.

Thank You
Neil R. Powe MD, MPH, MBA Vanessa Grubbs MD, MPH Addisu Melke MD

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