Mortality Risk Unchanged by Iron Dose in Hemodialysis Patients with Cancer

A new study at the 61st European Renal Association (ERA) Congress evaluated the impact of iron and erythropoiesis-stimulating agent (ESA) dose on mortality rates of patients on hemodialysis with cancer.¹

In the management of patients on hemodialysis with cancer, administration of iron was not associated with an increased mortality risk, supporting the continuation of intravenous use without any additional risk. However, the study could not confirm the safety of increasing ESA doses in these patients, potentially due to the small sample size.

“These results need to be confirmed in a larger population to define guidelines for iron and ESA use in hemodialysis patients with cancer,” said presenting investigator Arthur Michon-Colin, Hôpital Bicêtre, Assistance Publique—Hôpitaux de Paris, Le Kremlin-Bicêtre.

ESAs and iron administration are often necessary for hemodialysis treatment, but evidence has shown a higher risk of cancer after ESA in patients on hemodialysis. Other studies have reported the potential for iron administration to promote metastasis.

In this study, Michon-Colin and colleagues sought to evaluate the association between iron and ESA administration with an increased risk of mortality among patients on hemodialysis with cancer. The retrospective, multi-center study included individuals >18 years old undergoing hemodialysis with cancer diagnosed during treatment in 10 facilities.

Data were collected each trimester, from 1 year before cancer diagnosis to the year after diagnosis, between September 2009 and March 2021. The collected data types included key biological data, cumulative doses of iron and ESA, and fatal outcomes.

Michon-Colin and colleagues performed univariate analyses to evaluate the impact of iron or ESA on the mortality risk after modeling exposure pre- and post-cancer diagnosis. An adjusted multivariate analysis was conducted using baseline variables considered independently associated with mortality risk. Sensitivity analyses assessed the robustness of the primary results.

At baseline, 79 patients were identified, with a median follow-up of 2.2 years. Patients had an average age of 72 years and 30.4% were women. Biological analysis revealed baseline hemoglobin levels were on target, at 10.4 g/dL, and ferritin levels were considered high, at 412 ng/mL.

Moreover, the median total iron dose in one trimester was 600 mg and the median total ESA dose was 71 UI/kg/week. Primary comorbidities for the patient population were cardiovascular, including diabetes (31.6%), smoking (35.1%), and atrial fibrillation (29.1%). The duration of hemodialysis, before the diagnosis of cancer, was 3 years, with a small population (11.5%) of patients with a history of renal transplantation.

At one year of follow-up, 37 (47.4%) patients died, with a single patient lost to follow-up. The median cumulative dose of iron remained stable between 400 and 600 mg by trimester, while the median cumulative dose of ESA increased, particularly at 6 months. Median hemoglobin levels remained between 10 and 12 g/dL and ferritin levels rose moderately at 6 months and returned to dose equivalent before cancer diagnosis.

Across multivariate analysis, an association was found between all-cause mortality and the cumulative dose of ESA in the year before cancer diagnosis (hazard ratio [HR], 1.37 [95% CI, 1.03 - 1.83); P = .031). However, the team found no association between mortality and the cumulative dose of iron administered before the diagnosis of cancer.

In the year following cancer diagnosis, multivariate analysis demonstrated a potential association, without statistical significance, between all-cause mortality and cumulative dose of ESA (HR, 1.37 [95% CI, 0.95 to 1.98]; P = .092). Again, there was no association between mortality and the cumulative iron dose administered in the year after cancer diagnosis.

“To conclude, we present here the management of iron and ESA in hemodialysis patients diagnosed with cancer, the amount of iron administered was not associated with an increased risk of mortality,” Michon-Colin said. “This observation supports the continuation of intravenous iron use in these patients without any additional risk.”

References

1. _{Michon-Colin A, Lombardi Y, Seret G, Lavainne F, Testa A, Ayari H, Rostoker G, Urena Torres PA, Touzot M. Impact of iron and erythropoiesis-stimulating agent (ESA) dose mortality of hemodialysis (HD) patients with cancer. Presented at the 61st European Renal Association Congress. Stockholm, Sweden. May 23-26, 2024.}
2. _{Butler AM, Kshirsagar AV, Olshan AF, Nielsen ME, Wheeler SB, Brookhart MA. Trends in Anemia Management in Hemodialysis Patients with Cancer. Am J Nephrol. 2015;42(3):206-215. doi:10.1159/000440771}