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Anemia Treatment Delays Not Linked to Renal Event Risk in CKD

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Delayed anemia treatment with ESAs was not correlated with worse renal events but elevated the risk of cardiovascular events and all-cause mortality.

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

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