Introduction
End-stage renal disease (ESRD) is the final, irreversible stage of chronic kidney disease (CKD), requiring either dialysis or a complete transplant, and is considered the fastest-growing chronic health condition worldwide. Disproportionately, African Americans (AA) are affected by this disease, starting with incidence rates. In 2013, there were a reported 865 million cases in AAs, compared to 288 million in European Americans (EA). ESRD carries substantial morbidity, mortality, and healthcare burden for these patients, and this disparity is poorly explained by current research. This paper acknowledges that the disparity could be due to differences in baseline kidney function between AA and EA; however, it confirms that race-specific risk factors are the most influential in incidence rates and disease development.
Methods
Researchers applied a case-cohort study in which 86,000 participants were enrolled. They took a random probability sample of 737 ESRD cases in which 878% were AA, and 13% were white. The follow-up median was 9.3 years. The subcohort was a probability sample of 4,238, in which 70.8% was AA and 29.8% was white. Researchers applied multivariable Cox regression with sampling weights, restricted cubic splines for continuous variables such as age, eGFR, and BMI. Some covariates included age, sex, BMI, smoking status, education, income, hyperextension, diabetes, and histories of strokes. The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) was the standard formula used to estimate eGFR from serum creatinine, age, sex, and race. Patients were assessed for genetic variants found predominantly in individuals of African ancestry.
Results
If researchers found a low eGFR, patients had a significantly degraded kidney function. ESRD cases developed a much higher rate of hypertension than did the subcohort, showing rates of 85.9% and 54.9%, respectively. Interestingly, the study demonstrated a higher median eGFR in the AA cohort compared to the EA cohort, despite higher ESRD incidence. In summarizing ESRD incidence by race, AA experienced incidence rates 3 times higher than those of EA at 285/100,000 persons per year versus 79/100000 persons per year, respectively. Without eGFR adjustment as a variable in the statistical model, the HR value was 2.64. After full adjustment of the inclusion of eGFR, the hazard ratio value was 2.58. Thus, eGFR causes no significant difference in incidence rate discrepancies. AA patients consistently were at a higher ESRD risk than EA patients, whereas EA patients showed a steeper decline in relative HR in eGFR adjustments, signifying that eGFR is a stronger predictor of ESRD, more so in EA. True implications point to non-eGFR (race-specific) factors being the primary driving factor of ESRD risk.
In a certain range of eGFR values, black patients had a consistently higher ESRD risk than white patients, where, at lower values, the curves between AA and EA patients converged, which represents the elimination of any racial gap. This meant that at higher eGFR levels, race-specific factors are driving AA patients towards ESRD regardless of the health status of their kidneys. Once both races demonstrate extremely degraded kidney functions, ESRD risk becomes interchangeable regardless of race. Further, AA patients with high eGFR values (54% of all ESRD cases) developed ESRD within 6-7 years. To clarify, these are patients with preserved kidney function. These implications suggest aggressive progression of disease occurring in the early stages of CKD rather than the common occurrence of a slowly declining function of a deteriorated kidney.
Limitations
The researchers acknowledge the limitations in this study, prompting effective change for future research in this field. First, there were no baseline urine protein data. With proteinuria being a key CKD progression marker, this could partially explain racial disparities, but as it was omitted from this study, it could present a notable gap. Second, there were no follow-up creatinine measurements; researchers were unable to calculate eGFR slopes (tracking kidney function trajectory). Third, some of the self-reported covariates, such as diabetes and hypertension severity and/or control, could not be comprehensively characterized. Fourth, this study included data from only black and white Americans, limiting the generality of other ethnic groups. Finally, there were no time-varying covariates, meaning the possible changes in clinical status were not recorded.
Conclusion
African Americans face more than double the risk of developing ESRD than European Americans. This disparity is not explained by baseline kidney function, traditional cardiovascular risk factors, socioeconomic status, but rather by race-specific risk factors. Due to the convergence of racial risk standing at a very low eGFR value (<40), this suggests race-specific factors are most influential in early stages of chronic kidney disease, before the mechanisms of ESRD. Future research should focus on genotyping strategies to quantify genetic contribution to disparity, as well as identifying modifiable lifestyle and metabolic factors to drive rapid chronic kidney disease progression in AA with preserved eGFR.
