The Association Between Erythropoiesis Resistance Index and Clinical Outcomes in Hemodialysis Patients: A Nationwide Study

Abstract

Background: Although erythropoiesis-stimulating agent (ESA) therapy is fundamental for correcting anemia, excessive ESA administration is associated with increased risks. This study aimed to investigate the impact of the erythropoietin resistance index (ERI) on clinical outcomes in a population-based cohort of hemodialysis (HD) patients. Methods: This retrospective study analyzed datasets from patients who underwent periodic HD quality assessments and their claims data. Overall, we included 35,913 patients. Participants were divided into quartiles based on the ERI during the 6-month assessment period: Q1, Q2, Q3, and Q4 groups. Results: The 5-year survival rates were 68.8% (Q1), 67.8% (Q2), 66.9% (Q3), and 60.2% (Q4) (p < 0.001). Multivariable analysis showed the same trends as the univariable analysis. Additionally, a spline curve using the multivariable model indicated that the increased ERI was linked to all-cause mortality. However, cardiovascular events were not associated with ERI quartiles in Cox regression analyses. Subgroup analysis revealed that in most subgroups, the all-cause mortality was significantly higher in those with a high ERI than in those with a low ERI. Further analysis using the balanced cohort, which attenuated baseline characteristic differences, confirmed that the high mortality in those with a high ERI was maintained. Conclusions: Our population-based cohort study reveals an association between the ERI and all-cause mortality in HD patients.

Keywords: erythropoiesis resistance; erythropoiesis-stimulating agent; hemodialysis; mortality.

Figure 1

Study flowchart. Abbreviations: HD, hemodialysis, ERI, erythropoietin resistance index ((IU/week)/kg/(g/dL)); ESA, erythropoiesis-stimulating agent; Q1, first quartile; Q2, second quartile; Q3, third quartile; Q4, fourth quartile.

Figure 2

Kaplan–Meier curves by quartiles of the erythropoietin resistance index. (A) Patient survival and (B) cardiovascular event–free rates. p-values for pairwise comparisons with log-rank tests were added to the bottom of the graph. Abbreviations: Q1, first quartile; Q2, second quartile; Q3, third quartile; Q4, fourth quartile.

Figure 3

Spline curves illustrating hazard ratios and 95% confidence intervals for clinical outcomes according to the erythropoietin resistance index. (A) All-cause mortality. (B) Cardiovascular events. The solid line shows the hazard ratio estimated from the multivariable model with a reference point at 9.1 (IU/week)/kg/(g/dL) of the erythropoietin resistance index, the dashed line represents the hazard ratio of 1.0 (reference), and the gray shaded area indicates the 95% confidence interval.