The Effects of Race on Acute Kidney Injury: Comparison
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Please note this is a comparison between Version 2 by Dean Liu and Version 1 by Muzamil Olamide Hassan.

Racial disparities in incidence and outcomes of acute kidney injury (AKI) are pervasive and are driven in part by social inequities and other factors. It is well-documented that Black patients face higher risk of AKI and seemingly have a survival advantage compared to White counterparts. Various explanations have been advanced and suggested to account for this, including differences in susceptibility to kidney injury, severity of illness, and socioeconomic factors.

  • race
  • ethnicity
  • acute kidney injury

1. Introduction

Race can be defined “as a hierarchal human-grouping system, generating social classifications to identify, distinguish and marginalize some groups across nations, regions and the world. Race divides human populations into groups often based on physical appearance, social factors and cultural backgrounds” [1]. Race is a socio-political concept that is inseparably linked to health outcomes in individuals from minority racial status worldwide [2]. Race is not a biological concept.
Racial disparities in clinical outcomes of several health conditions are very common [3]. Such disparities have been reported in AKI, where Black race is associated with a higher risk of AKI compared to non-Black race [4]. Moreover, the prevalence of dialysis-requiring AKI is increasing annually, and Black race is an independent risk factor for initiation of dialysis in AKI patients [4,5,6,7,8][4][5][6][7][8]. This phenomenon is thought to be due to the close interplay of clinical, socioeconomic, and genetic risk factors [9], which are driven by structural racial category [10].
Acute kidney injury describes the sudden loss of kidney function, characterized by ≥0.3 mg/dL (≥26.5 μmol/L) rise in serum creatinine within 48 h or an increase in serum creatinine ≥1.5 times over baseline, which is known or presumed within the prior 7 days, or reduced urinary output of < 0.5 mL/kg/h within 6 h [11]. Given that AKI has significant clinical consequences, including higher hospitalization rates, increased hospital length of stay, increased in-hospital and post-hospitalization mortality, and higher risk of progression to chronic kidney disease [12[12][13][14][15],13,14,15], understanding and addressing how race directly affects patients with AKI is crucial to improving the diagnosis, treatment, and outcomes of AKI in minority racial groups.

2. Racial Disparities in the Incidence of AKI

Previous studies have reported that Black patients have a disproportionately higher risk of AKI when compared with White patients [4,8,16,17,18,19,20,21,22][4][8][16][17][18][19][20][21][22]. Using self-reported Black and White participants from the Atherosclerosis Risk in Communities (ARIC) study, Grams et al. [4] investigated the impact of race on the incidence of AKI-related hospitalizations. The authors in the large, prospective, community-based studies involving 10,588 African-American and Caucasian participants followed up for 13 years reported significantly higher incidence of AKI in Blacks, with a 30% higher risk in Blacks compared to Whites. After a sequential multivariable model, the risk increased to 50% following the inclusion of age and sex, suggesting that Blacks are at a greater risk of AKI despite their younger age. However, the risks were not significantly different among those participants with major mediators such as obesity, diabetes, or hypertension, which are more common in Blacks compared to Whites. The authors further showed that the relationship between race and AKI was significantly weakened with adjustment for socio-economic indicators such as access to health insurance and total annual family income. Similarly, other studies have reported significantly higher incidence of AKI along racial lines among specialized populations, including patients with diabetes [17], trauma [20], and those undergoing procedures such as percutaneous coronary intervention [8,21][8][21] and knee surgery [19]. In contrast to the findings of Grams et al. [4] in the ARIC study, Muiru and his colleagues, in the Chronic Renal Insufficiency Cohort (CRIC) Study, a multicenter prospective study, observed that Blacks had a 22% greater hazard for AKI hospitalization than the Whites, and showed that the racial disparities in AKI were due to the differences in prehospitalization baseline clinical risk factors such as diabetes, blood pressure, and proteinuria [22]. Thus, this suggested that the increased risk of AKI among Black individuals may be mitigated through targeted screening and tighter control of blood pressure to lower proteinuria. Taken together, all these findings highlight the need for future studies to untie the “Gordian knot” between socio-economic determinants of AKI from those that might be biologic, if any. Moreover, according to the 2018 USRDS annual data report [23], using data from the Medicare, ClinformaticsTM, (OptumInsight, Eden Prairie, MN, USA) and Veterans Affairs patient population, a higher proportion of Black patients had AKI compared to Whites or Asians. Among Medicare patients aged 66 years and older, AKI incidence rates were 34.3%, 23%, and 25.9% in Black, White, and Asian patients, respectively, and for Optum Clinformatics™ (OptumInsight, Eden Prairie, MN, USA) patients aged 22 years and older, the incidence of AKI among Black, White, and Asian patients was 9.4%, 7.4%, and 3.3%, respectively. The hospitalized Veterans Affairs populations showed a similar trend—the incidence of AKI was 30.4%, 24.1%, and 24.2% among Black, White, and Asian Americans, respectively. These data therefore highlight differences in AKI incidence by race. 

3. Race, APOL1 Status, and Incidence of AKI

Considering the well-established genetic susceptibility for kidney disease among Black populations [33[24][25],34], it was not surprising that Privratsky et al. [35][26] demonstrated a greater-than-two-fold rise in postoperative serum creatinine among Black patients with high-risk APOL1 status undergoing cardiac surgery. However, a previous study by Grams et al. [4] showed that APOL1 high-risk variant was not significantly associated with higher risk of AKI. Thise study was limited by reliance on billing codes to ascertain AKI, thereby resulting in ill-defined AKI phenotypes. Given that there are several recent reports of association between high-risk APOL1 status and increased risk of AKI among patients infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) [35,36,37,38,39,40[26][27][28][29][30][31][32],41], further studies are needed to elucidate APOL1 biology, its role in well-defined AKI cases, and its possible modifying effect on progression to CKD after injury.

4. Race and COVID-19-Related AKI

Acute kidney injury is a well-recognized complication of SARS-CoV-2 infection, with an incidence rate of 20% among hospitalized patients and greater than 50% among the critically ill patients [42][33]. Since the first case of SARS-CoV-2 infection which causes coronavirus disease 2019 (COVID-19) was reported in Wuhan, China, racial disparities in the development, severity, and outcomes of this disease have become increasingly reported [43,44,45][34][35][36]. According to the Centers for Disease Control, Blacks had a 1.1 times higher rate of COVID-19 patients, 2.3 times higher rate of COVID-19 hospitalization, and 1.7 times higher COVID-19 mortality rate than Whites [46][37]. Accordingly, several previous studies have reported that Black patients with COVID-19 had approximately 1.2–2.2 times increased odds of developing in-hospital AKI compared to their White counterparts [47,48,49,50][38][39][40][41]. Even though the exact mechanism of racial disparities in risk of COVID-associated AKI is yet to be elucidated, some possible mechanisms have been proposed. Genetic polymorphisms involving ACE2, IL-6, and AChE genes are closely associated with higher burden of COVID-19 disease and these gene polymorphisms have been shown to be more common in Black individuals [51,52][42][43]. In addition, Black populations are exposed to a higher risk of vitamin D deficiency, and it has been proposed that Vitamin D plays a protective role against COVID-19 infectivity and severity through its ability to modulate the immune system by suppressing T helper-1 functions and potentiating expression of the regulatory T cells, thereby causing less severe cytokine storm [53,54][44][45]. Hence, Black patients may face higher risk of cytokine storm and associated systemic and intrarenal inflammation.

References

  1. Available online: https://www.genome.gov/genetics-glossary/Race (accessed on 22 July 2022).
  2. Eneanya, N.D.; Boulware, L.E.; Tsai, J.; Bruce, M.A.; Ford, C.L.; Harris, C.; Morales, L.S.; Ryan, M.J.; Reese, P.P.; Thorpe, R.J., Jr.; et al. Health inequities and the inappropriate use of race in nephrology. Nat. Rev. Nephrol. 2022, 18, 84–94.
  3. Biello, K.B.; Rawlings, J.; Carroll-Scott, A.; Browne, R.; Ickovics, J.R. Racial disparities in age at preventable hospitalization among U.S. Adults. Am. J. Prev. Med. 2010, 38, 54–60.
  4. Grams, M.E.; Matsushita, K.; Sang, Y.; Estrella, M.; Foster, M.; Tin, A.; Kao, W.H.; Coresh, J. Explaining the racial difference in AKI incidence. J. Am. Soc. Nephrol. 2014, 25, 1834–1841.
  5. Hsu, R.K.; McCulloch, C.E.; Dudley, R.A.; Lo, L.J.; Hsu, C.Y. Temporal changes in incidence of dialysis-requiring AKI. J. Am. Soc. Nephrol. 2013, 24, 37–42.
  6. Norris, K.C.; Agodoa, L.Y. Unraveling the racial disparities associated with kidney disease. Kidney Int. 2005, 68, 914–924.
  7. Nicholas, S.B.; Kalantar-Zadeh, K.; Norris, K.C. Racial disparities in kidney disease outcomes. Semin. Nephrol. 2013, 33, 409–415.
  8. Lunyera, J.; Clare, R.M.; Chiswell, K.; Scialla, J.J.; Pun, P.H.; Thomas, K.L.; Starks, M.A.; Diamantidis, C.J. Rcial Differences in AKI Incidence Following Percutaneous Coronary Intervention. J. Am. Soc. Nephrol. 2021, 32, 654–662.
  9. Norton, J.M.; Moxey-Mims, M.M.; Eggers, P.W.; Narva, A.S.; Star, R.A.; Kimmel, P.L.; Rodgers, G.P. Social Determinants of Racial Disparities in CKD. J. Am. Soc. Nephrol. 2016, 27, 2576–2595.
  10. Bailey, Z.D.; Krieger, N.; Agénor, M.; Graves, J.; Linos, N.; Bassett, M.T. Structural racism and health inequities in the USA: Evidence and interventions. Lancet 2017, 389, 1453–1463.
  11. KDIGO clinical practice guidelines for acute kidney injury. Kidney Int. 2012, 2, 1–138.
  12. Chawla, L.S.; Eggers, P.W.; Star, R.A.; Kimmel, P.L. Acute kidney injury and chronic kidney disease as interconnected syndromes. N. Engl. J. Med. 2014, 371, 58–66.
  13. Koulouridis, I.; Price, L.L.; Madias, N.E.; Jaber, B.L. Hospital-acquired acute kidney injury and hospital readmission: A cohort study. Am. J. Kidney Dis. 2015, 65, 275–282.
  14. Rewa, O.; Bagshaw, S.M. Acute kidney injury-epidemiology, outcomes and economics. Nat. Rev. Nephrol. 2014, 10, 193–207.
  15. Hassan, M.O.; Owoyemi, I.; Abdel-Rahman, E.M.; Ma, J.Z.; Balogun, R.A. Association of Race with In-Hospital and Post-Hospitalization Mortality in Patients with Acute Kidney Injury. Nephron 2021, 145, 214–224.
  16. Xue, J.L.; Daniels, F.; Star, R.A.; Kimmel, P.L.; Eggers, P.W.; Molitoris, B.A.; Himmelfarb, J.; Collins, A.J. Incidence and mortality of acute renal failure in Medicare beneficiaries, 1992 to 2001. J. Am. Soc. Nephrol. 2006, 17, 1135–1142.
  17. Mathioudakis, N.N.; Giles, M.; Yeh, H.C.; Haywood, C.J.; Greer, R.C.; Golden, S.H. Racial differences in acute kidney injury of hospitalized adults with diabetes. J. Diabetes Complicat. 2016, 30, 1129–1136.
  18. Grams, M.E.; Sang, Y.; Ballew, S.H.; Gansevoort, R.T.; Kimm, H.; Kovesdy, C.P.; Naimark, D.; Oien, C.; Smith, D.H.; Coresh, J.; et al. A Meta-analysis of the Association of Estimated GFR, Albuminuria, Age, Race, and Sex with Acute Kidney Injury. Am. J. Kidney Dis. 2015, 66, 591–601.
  19. Womble, T.N.K.J.; Hamilton, D.H.; Shrout, M.A.; Jacobs, C.A.; Duncan, S.T. Greater rates of acute kidney injury in African American total knee arthroplasty patients. J. Arthroplast. 2019, 34, 1240–1243.
  20. Shashaty, M.G.; Meyer, N.J.; Localio, A.R.; Gallop, R.; Bellamy, S.L.; Holena, D.N.; Lanken, P.N.; Kaplan, S.; Yarar, D.; Kawut, S.M.; et al. African American race, obesity, and blood product transfusion are risk factors for acute kidney injury in critically ill trauma patients. J. Crit. Care 2012, 27, 496–504.
  21. Kobayashi, T.; Glorioso, T.J.; Armstrong, E.J.; Maddox, T.M.; Plomondon, M.E.; Grunwald, G.K.; Bradley, S.M.; Tsai, T.T.; Waldo, S.W.; Rao, S.V.; et al. Comparative Outcomes After Percutaneous Coronary Intervention Among Black and White Patients Treated at US Veterans Affairs Hospitals. JAMA Cardiol. 2017, 2, 967–975.
  22. Muiru, A.N.; Yang, J.; Derebail, V.K.; Liu, K.D.; Feldman, H.I.; Srivastava, A.; Bhat, Z.; Saraf, S.L.; Chen, T.K.; He, J.; et al. Black and White Adults with CKD Hospitalized with Acute Kidney Injury: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study. Am. J. Kidney Dis. 2022.
  23. United States Renal Data System. 2018 USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States; National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases: Bethesda, MD, USA, 2018.
  24. Tzur, S.; Rosset, S.; Shemer, R.; Yudkovsky, G.; Selig, S.; Tarekegn, A.; Bekele, E.; Bradman, N.; Wasser, W.G.; Behar, D.M.; et al. Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene. Hum. Genet. 2010, 128, 345–350.
  25. Genovese, G.; Friedman, D.J.; Ross, M.D.; Lecordier, L.; Uzureau, P.; Freedman, B.I.; Bowden, D.W.; Langefeld, C.D.; Oleksyk, T.K.; Uscinski Knob, A.L.; et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 2010, 329, 841–845.
  26. Privratsky, J.R.; Li, Y.J.; Haynes, C.; Podgoreanu, M.; Mathew, J.; Shah, S.H.; Stafford-Smith, M. Apolipoprotein L1 (APOL1) Coding Variants are Associated with Creatinine Rise After Cardiac Surgery. J. Cardiothorac. Vasc. Anesth. 2020, 34, 3314–3320.
  27. Hung, A.M.; Shah, S.C.; Bick, A.G.; Yu, Z.; Chen, H.C.; Hunt, C.M.; Wendt, F.; Wilson, O.; Greevy, R.A.; Chung, C.P.; et al. APOL1 Risk Variants, Acute Kidney Injury, and Death in Participants with African Ancestry Hospitalized with COVID-19 from the Million Veteran Program. JAMA Intern. Med. 2022, 182, 386–395.
  28. Magoon, S.; Bichu, P.; Malhotra, V.; Alhashimi, F.; Hu, Y.; Khanna, S.; Berhanu, K. COVID-19-Related Glomerulopathy: A Report of 2 Cases of Collapsing Focal Segmental Glomerulosclerosis. Kidney Med. 2020, 2, 488–492.
  29. Kudose, S.; Batal, I.; Santoriello, D.; Xu, K.; Barasch, J.; Peleg, Y.; Canetta, P.; Ratner, L.E.; Marasa, M.; Gharavi, A.G.; et al. Kidney Biopsy Findings in Patients with COVID-19. J. Am. Soc. Nephrol. 2020, 31, 1959–1968.
  30. Kissling, S.; Rotman, S.; Gerber, C.; Halfon, M.; Lamoth, F.; Comte, D.; Lhopitallier, L.; Sadallah, S.; Fakhouri, F. Collapsing glomerulopathy in a COVID-19 patient. Kidney Int. 2020, 98, 228–231.
  31. Larsen, C.P.; Bourne, T.D.; Wilson, J.D.; Saqqa, O.; Sharshir, M.A. Collapsing Glomerulopathy in a Patient with COVID-19. Kidney Int. Rep. 2020, 5, 935–939.
  32. Peleg, Y.; Kudose, S.; D’Agati, V.; Siddall, E.; Ahmad, S.; Nickolas, T.; Kisselev, S.; Gharavi, A.; Canetta, P. Acute Kidney Injury Due to Collapsing Glomerulopathy Following COVID-19 Infection. Kidney Int. Rep. 2020, 5, 940–945.
  33. Nadim, M.K.; Forni, L.G.; Mehta, R.L.; Connor, M.J.; Liu, K.D.; Ostermann, M.; Rimmelé, T.; Zarbock, A.; Bell, S.; Bihorac, A.; et al. COVID-19-associated acute kidney injury: Consensus report of the 25th acute disease quality initiative (ADQI) workgroup. Nat. Rev. Nephrol. 2020, 16, 747–764.
  34. Hu, B.; Guo, H.; Zhou, P.; Shi, Z.L. Characteristics of SARS-CoV-2 and COVID-19. Nat. Rev. Microbiol. 2020, 19, 141–154.
  35. The Lancet Infectious Disease. COVID-19, a pandemic or not? Lancet Infect. Dis. 2020, 20, 383.
  36. Kullar, R.; Marcelin, J.R.; Swartz, T.H.; Piggott, D.A.; Macias Gil, R.; Mathew, T.A.; Kullar, R.; Marcelin, J.R.; Swartz, T.H.; Piggott, D.A.; et al. Racial Disparity of Coronavirus Disease 2019 in African American Communities. J. Infect. Dis. 2020, 222, 890–893.
  37. Risk for COVID-19 Infection H, and Death by Race/Ethnicity. Available online: https://www.cdc.gov/coronavirus/2019-ncov/covid-data/investigations-discovery/hospitalization-death-by-race-ethnicity.html (accessed on 27 July 2022).
  38. Charoenngam, N.; Ilori, T.O.; Holick, M.F.; Hochberg, N.S.; Apovian, C.M. Self-identified Race and COVID-19-Associated Acute Kidney Injury and Inflammation: A Retrospective Cohort Study of Hospitalized Inner-City COVID-19 Patients. J. Gen. Intern. Med. 2021, 36, 3487–3496.
  39. Nimkar, A.; Naaraayan, A.; Hasan, A.; Pant, S.; Durdevic, M.; Suarez, C.N.; Elenius, H.; Hambardzumyan, A.; Lakshmi, K.; Mandel, M.; et al. Incidence and Risk Factors for Acute Kidney Injury and Its Effect on Mortality in Patients Hospitalized from COVID-19. Mayo Clin. Proc. Innov. Qual. Outcomes 2020, 4, 687–695.
  40. Hirsch, J.S.; Ng, J.H.; Ross, D.W.; Sharma, P.; Shah, H.H.; Barnett, R.L.; Barnett, R.L.; Hazzan, A.D.; Fishbane, S.; Jhaveri, K.D.; et al. Acute kidney injury in patients hospitalized with COVID-19. Kidney Int. 2020, 98, 209–218.
  41. Bowe, B.; Cai, M.; Xie, Y.; Gibson, A.K.; Maddukuri, G.; Al-Aly, Z. Acute Kidney Injury in a National Cohort of Hospitalized US Veterans with COVID-19. Clin. J. Am. Soc. Nephrol. 2021, 16, 14–25.
  42. Phillips, N.; Park, I.W.; Robinson, J.R.; Jones, H.P. The Perfect Storm: COVID-19 Health Disparities in US Blacks. J. Racial Ethn. Health Disparities 2020, 8, 1153–1160.
  43. Vinciguerra, M.; Greco, E. Sars-CoV-2 and black population: ACE2 as shield or blade? Infect. Genet. Evol. 2020, 84, 104361.
  44. Holick, M.F. Vitamin D deficiency. N. Engl. J. Med. 2007, 357, 266–281.
  45. Charoenngam, N.; Shirvani, A.; Holick, M.F. Vitamin D and Its Potential Benefit for the COVID-19 Pandemic. Endocr. Pract. 2021, 27, 484–493.
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