Anemia Treatment Delays Not Linked to Renal Event Risk in CKD

Delays in anemia treatment with erythropoiesis-stimulating agents (ESAs) were not linked to worse renal outcomes in patients with nondialysis-dependent chronic kidney disease (NDD-CKD), according to the results of a retrospective cohort study.¹

These data, instead, pointed to an elevated risk of cardiovascular events and all-cause mortality for those who received delayed ESA therapy, suggesting the importance of early intervention before hemoglobin levels hit below 9.0 g/dL.

“Our study provides new insights into clinical practice regarding hemoglobin levels at the start of long-acting ESA treatment and outcomes in patients with anemia in NDD-CKD, for which there has been little evidence to date,” wrote the investigative team, led by Kouji Kawai, Mitsubishi Tanabe Pharma Corporation.

Approximately 850 million people globally are impacted by CKD – anemia is common in CKD, with an increasing prevalence matching its severity, and is linked to a reduced quality of life and higher risk of cardiovascular events.²

The standard treatment for anemia in CKD is ESA therapy alongside iron supplementation.³ However, there are limited reports on the association between hemoglobin level at therapy initiation and renal and cardiovascular outcomes in patients with anemia in NDD-CKD.

In this retrospective study, Kawai and colleagues explored 2 Japanese databases to investigate these outcomes in Japanese patients with anemia in NDD-CKD.¹ Key inclusion criteria included a first prescription of darbepoetin alfa or continuous erythropoietin receptor activator between January 2011 and December 2018 and a diagnosis of renal anemia at the same point as the index date.

Those matching inclusion criteria were divided into 2 groups according to hemoglobin levels 30 days before the index date: early treatment (hemoglobin ≥9.0 g/dL) and delayed treatment (<9.0 g/dL). The study’s primary outcome was a renal composite of renal replacement therapy, a reduction of ≥50% in estimated glomerular filtration rate (eGFR) and an eGFR <6.0 ml/min per 1.73 m2 at 2 consecutive measurements, and all-cause mortality.

After propensity score matching was performed, the study evaluated 1472 and 1264 patients from the MDV and RWD databases, respectively. Upon analysis, Kaplan-Meier cumulative incidence curves of the renal composite outcomes demonstrated no notable difference between the early and delayed treatment groups.

Specifically, delayed treatment was not associated with a risk of the renal composite outcome across the MDV (hazard ratio [HR], 1.15; 95% CI, 0.99–1.33) and RWD (HR, 1.08; 95% CI, 0.92–1.28) databases.

On the other hand, the risks for all-cause mortality were significantly increased in those with delays in treatment, compared with the early treatment group, in both the MDV (HR, 1.83; 95% CI, 1.32–2.54) and the RWD (HR, 1.64; 95% CI, 1.21–2.22) databases.

Cardiovascular outcomes also revealed significant differences between the early and delayed treatment group curves across the MDV (P = .001) and RWD data sets (P = .006). The risk for the cardiovascular composite outcome was significantly increased in the delayed treatment group in the MDV (HR, 1.47; 95% CI, 1.16–1.84) and RWD (HR, 1.34; 95% CI, 1.09–1.63) databases.

Moreover, risks for heart failure were significantly higher in the delayed treatment group in both the MDV data set (HR,1.50; 95% CI, 1.13–2.00) and the RWD data set (HR, 1.53; 95% CI, 1.20–1.96).

“Combined with the findings of the present study, earlier intervention than current practice for anemia in NDD-CKD may be desirable to avoid cardiovascular events and mortality in these patients,” Kawai and colleagues wrote.

References

1. _{Kawai K, Ishii M, Kokado Y, Horikawa T, Hoshino J. Outcomes of Early Versus Delayed Anemia Treatment in Nondialysis-Dependent CKD. Kidney Int Rep. 2024;9(7):2056-2066. Published 2024 Apr 15. doi:10.1016/j.ekir.2024.04.030}
2. _{Jager KJ, Kovesdy C, Langham R, Rosenberg M, Jha V, Zoccali C. A single number for advocacy and communication-worldwide more than 850 million individuals have kidney diseases. Kidney Int. 2019;96(5):1048-1050. doi:10.1016/j.kint.2019.07.012}
3. _{Lamerato L, James G, van Haalen H, et al. Epidemiology and outcomes in patients with anemia of CKD not on dialysis from a large US healthcare system database: a retrospective observational study. BMC Nephrol. 2022;23(1):166. Published 2022 Apr 30. doi:10.1186/s12882-022-02778-8}