Black individuals, who are at a two- to fourfold higher risk of developing end stage kidney disease in the United States, are simultaneously less likely to be referred for transplantation, to be waitlisted, or to receive a kidney transplant (KT) (1–3).
The murders of countless Black individuals sparked uprisings in 2020 throughout the United States. This included efforts spearheaded by medical students around the country to remove race as a factor in estimated glomerular filtration rate (eGFR) calculation at their institutions (4). Racialized algorithms, which include race in eGFR equations, result in higher values for individuals identified as Black, potentially delaying KT eligibility (5). As described by the following points, race: 1) lacks biological meaning, 2) is dynamic and contextually sensitive in how and by whom it is defined, and 3) often reinforces erroneous beliefs regarding the inferiority and “otherness” of minoritized groups (6, 7). Race-based medicine perpetuates race as a biological variable, rather than a social construct, contributing to inequities and healthcare disparities (6).
In fall 2021, the final report from a National Kidney Foundation and American Society of Nephrology Task Force to reassess inclusion of race in eGFR recommended “immediate implementation of the Chronic Kidney Disease Epidemiology Collaboration creatinine equation refit without the race variable” (8).
Unfortunately, the eGFR calculation is not the only arena within nephrology that must implement “race correction.” The kidney donor risk index (KDRI), implemented in 2014, uses 10 donor characteristics (Table 1), including self-reported race, to predict the relative risk of allograft failure. The kidney donor profile index (KDPI), derived from the KDRI, maps the KDRI relative risk to a cumulative percentage scale (i.e., a KDPI of 85% indicates a KDRI greater than 85% of recovered kidneys). Higher KDPI values are associated with lower longevity and donor quality and thus can impact organ acceptance practices by transplant clinicians. Furthermore, deceased donor kidneys with low KDPIs are allocated to those individuals with longer estimated posttransplant survival (EPTS), which is calculated using the recipient's age, dialysis vintage, diabetes status, and history of prior organ transplants (9).
Variables included in the KDRI model, with estimated coefficients
The KDRI was the result of a 2009 study in which a multivariable Cox regression model was estimated using allograft outcomes from 69,440 deceased donor KT recipients in the United States from 1995 to 2005 (Table 1) (10). Although not explained in the manuscript, race was likely included as a variable due to the prior observation that kidneys from Black donors were associated with a higher risk of allograft loss (11). Like eGFR equations that include race, inclusion in the KDRI calculation similarly implicates race as a biological variable. Rather than race, it is likely that these differences may be better explained by biological factors and unequal social determinants of health. The KDRI hazard ratio for Black race was estimated to be 1.20—higher than that for a donor with a history of hypertension or diabetes, donation after cardiac death, or cerebrovascular accident as the cause of death—increasing the risk of estimated allograft failure by 20%. The liver donor risk index (LDRI) similarly includes race, with a 1.2 hazard ratio for Black versus White donors (12). As we seek an unbiased and more accurate and precise model toward eGFR, we must do the same to assess kidney donor quality to improve equity in kidney transplantation. One potential solution is the inclusion of the apolipoprotein L1 (APOL1) genotype, as allografts with high kidney risk variants (KRVs) have been associated with early allograft failure (13). A 2017 retrospective cohort study of 1149 KT recipients concluded that replacing race with the APOL1 genotype (0/1 KRV vs. 2 KRVs) improved risk estimation for kidneys from Black donors and improved the KDRI for 85%–90% of kidneys offered (14). In current clinical practice, waiting for deceased donor APOL1 genotyping results for KDRI calculation may significantly prolong cold ischemia time. The APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) study may shed further light on the impact of KRVs on allograft outcomes (15). Furthermore, a recent analysis of Scientific Registry of Transplant Recipients data from 2000 to 2017 found that removal of race from the KDRI calculation did not alter the overall predictability of allograft failure or patient survival (16).
As we seek an unbiased and more accurate and precise model toward eGFR, we must do the same to assess kidney donor quality to improve equity in kidney transplantation.
Until these newer models and coefficients can be estimated without race, transplant centers may consider re-calculation of KDRI without the race coefficient when making decisions regarding acceptance of organs or immunosuppression regimens. Furthermore, advances in the treatment of hepatitis C virus (HCV) that have allowed for the transplantation of kidneys from HCV-infected donors into HCV-negative recipients beg for a new donor quality assessment tool (17). It is imperative that the Organ Procurement and Transplant Network (OPTN) and United Network for Organ Sharing (UNOS) interrogate the current calculation of the KDRI and its potential impact on organ allocation and inequity in transplantation (Table 2) (18).
Comparison of KDPI among four hypothetical donors
References
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Boulware LE, et al. Systemic kidney transplant inequities for Black individuals: Examining the contribution of racialized kidney function estimating equations. JAMA Netw Open 2021; 4:e2034630. doi: 10.1001/jamanetworkopen.2020.34630
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Purnell TS, et al. Association of race and ethnicity with live donor kidney transplantation in the United States from 1995 to 2014. JAMA 2018; 319:49–61. doi: 10.1001/jama.2017.19152
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Sood A, et al. Rates of kidney transplantation from living and deceased donors for Blacks and Whites in the United States, 1998 to 2011. JAMA Intern Med 2015; 175:1716–1718. doi: 10.1001/jamainternmed.2015.4530
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Balch B. Confronting race in diagnosis: Medical students call for reexamining how kidney function is estimated [internet]. Association of American Medical Colleges (AAMC). September 24, 2020. https://www.aamc.org/news-insights/confronting-race-diagnosis-medical-students-call-reexamining-how-kidney-function-estimated
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Zelnick LR, et al. Association of the estimated glomerular filtration rate with vs without a coefficient for race with time to eligibility for kidney transplant. JAMA Netw Open 2021; 4:e2034004. doi: 10.1001/jamanetworkopen.2020.34004
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Cerdeña JP, et al. From race-based to race-conscious medicine: How anti-racist uprisings call us to act. Lancet 2020; 396:1125–1128. doi: 10.1016/S0140-6736(20)32076-6
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Mohottige D, et al. Racism and kidney health: Turning equity into a reality. Am J Kidney Dis 2021; 77:951–962. doi: 10.1053/j.ajkd.2021.01.010
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Delgado C, 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. J Am Soc Nephrol [published online ahead of print September 23, 2021]. doi: 10.1681/ASN.2021070988; https://jasn.asnjournals.org/content/early/2021/11/08/ASN.2021070988
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US Department of Health and Human Services. Organ Procurement and Transplantation Network. EPTS calculator [internet]. Accessed November 15, 2021. https://optn.transplant.hrsa.gov/resources/allocation-calculators/epts-calculator/
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Akkina SK, et al. Development of organ-specific donor risk indices. Liver Transpl 2012; 18:395–404. doi: 10.1002/lt.23398
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Freedman BI, et al. APOL1 genotype and kidney transplantation outcomes from deceased African American donors. Transplantation 2016; 100:194–202. doi: 10.1097/TP.0000000000000969
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Julian BA, et al. Effect of replacing race with apolipoprotein L1 genotype in calculation of kidney donor risk index. Am J Transplant 2017; 17:1540–1548. doi: 10.1111/ajt.14113
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Freedman BI, et al. APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO): Design and rationale. Kidney Int Rep 2019; 5:278–288. doi: 10.1016/j.ekir.2019.11.022
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Chong K, et al. Donor race has no role in predicting allograft and patient survival among kidney transplant recipients. medRxiv April 7, 2021. https://www.medrxiv.org/content/10.1101/2021.04.01.21254772v1
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Reese PP, et al. Twelve-month outcomes after transplant of hepatitis C-infected kidneys into uninfected recipients: A single-group trial. Ann Intern Med 2018; 169:273–281. doi: 10.7326/M18-0749
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US Department of Health and Human Services. Organ Procurement and Transplantation Network. KDPI calculator [internet]. Accessed November 15, 2021. https://optn.transplant.hrsa.gov/resources/allocation-calculators/kdpi-calculator/
