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Greater Hemoglobin Variability on ESAs Ups Infection Risk

Higher variability in hemoglobin levels while on erythropoiesis-stimulating agents (ESAs) is associated with increased risks for infection, thrombotic events, and all-cause mortality in patients on hemodialysis, a study finds.

In a study of 3063 patients from the Japanese Dialysis Outcomes and Practice Patterns Study, the risk for all-cause mortality trended higher in the higher quartiles of hemoglobin variability, compared with the lowest quartile. The risk for death was 44% higher for quartile 4 vs 1, although the increased risk was not statistically significant, Hiroshi Nishi, MD, of The University of Tokyo Graduate School of Medicine in Tokyo, Japan, and colleagues reported in Kidney International Reports. Patients without iron supplementation were particularly susceptible. Hospitalization risk increased 18% for patients in quartile 4 vs 1.

Quartile 1 of hemoglobin variability was defined as less than 1.2 g/dL, and quartiles 2, 3 and 4 as 1.2 to 1.7, 1.8 to 2.5, and 2.6 g/dL or higher, respectively.

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Infectious events occurred in 4.5 per 100 person-years, respectively. The investigators found that patients in the second, third, and fourth quartiles of hemoglobin variability had an infection risk more than 1.5-fold higher compared with the lowest quartile. The risk for infectious events was more pronounced among patients with ferritin values less than 100 ng/mL and those receiving iron supplementation.

With respect to infection risk, higher hemoglobin variability may lead to fluctuations in oxygen delivery to the immune organs and cells, the investigators suggested. Higher than usual hemoglobin variability may also reflect a systemic condition that jeopardizes immunity.

Whether treatment of anemia with long-acting ESAs can stabilize hemoglobin levels and decrease hemoglobin variability is uncertain, the investigators noted.

“Further research is required to clarify the underlying mechanism of the deteriorative effect of hemoglobin variability and iron homeostasis on host defenses in patients with end-stage kidney disease,” Dr Nishi’s team wrote. “Whether modification of hemoglobin variability in those high-risk cohorts might improve their clinical outcomes also warrants further investigation.”

Disclosure: This research was supported by Kyowa Kirin Co. Please see the original reference for a full list of disclosures.


Nishi H, Wang J, Onishi Y, Nangaku M. Infectious risk and variability of hemoglobin level in patients undergoing hemodialysis. Kidney Int Rep. Published online June 14, 2023. doi:10.1016/j.ekir.2023.06.004