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. 2024 Nov 25;25(1):423.
doi: 10.1186/s12882-024-03877-4.

Erythrocyte indices and response to hypoxia-inducible factor prolyl hydroxylase inhibitors in chronic kidney disease patients with renal anemia: a retrospective study

Kohei Odajima  1 , Shigeyuki Arai  1 , Ryo Kido  2   3 , Hitoshi Anzai  1 , Maika Gojo  1 , Shuntaro Taira  1 , Rena Matsui  1 , Yoshihide Fujigaki  1 , Shigeru Shibata  4   5
Affiliations

Erythrocyte indices and response to hypoxia-inducible factor prolyl hydroxylase inhibitors in chronic kidney disease patients with renal anemia: a retrospective study

Kohei Odajima et al. BMC Nephrol. .

Abstract

Background: Although erythropoiesis-stimulating agents (ESAs) have been the standard treatment for renal anemia, ESA hyporesponsiveness remains a concern. Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of agents indicated for renal anemia. Several lines of evidence indicate that HIF-PHIs affect erythrocyte indices; nonetheless, their clinical significance remains unclear.

Methods: We retrospectively analyzed data from 233 non-dialysis-dependent chronic kidney disease patients who initiated either ESA (darbepoetin) or HIF-PHI for the treatment of anemia. We analyzed the changes in hemoglobin levels three months after the initiation of anti-anemic treatments, examining their association with changes in erythrocyte indices.

Results: Both ESA and HIF-PHIs significantly increased hemoglobin levels after three months of treatment. In the HIF-PHI group, the increase in hemoglobin levels was positively correlated with the increase in mean corpuscular volume (MCV) levels, a finding that was not observed in the ESA group. In a subgroup analysis based on the mean reference range value for MCV (90.9 fL), a significant difference in the proportion of patients with improved anemia was observed between ESA and HIF-PHIs in patients with lower MCV values. Logistic regression and interaction analyses confirmed that there was a significant interaction between baseline MCV values and the effectiveness of anti-anemic drugs, independently of other covariates.

Conclusions: An increase in hemoglobin levels is associated with an increase in MCV in patients treated with HIF-PHIs. The anti-anemic effects of ESA and HIF-PHIs may be influenced by baseline MCV values. However, long-term consequences need further evaluation.

Keywords: Anemia; CKD; ESA; Erythropoiesis; HIF-PHI.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of Teikyo University School of Medicine with a waiver of the requirement for obtaining written informed consent due to its retrospective nature (No. 22-059-2). The study was conducted in accordance with the principles of the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: S.S. received personal fees and/or research funding from Bayer, Kyowa-Kirin, and Torii.

Figures

Fig. 1
Fig. 1
Increase in Hb levels positively associates with changes in mean corpuscular volume (MCV) in patients receiving hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) but not in those receiving erythropoiesis-stimulating agents (ESA). (A) Changes in hemoglobin (Hb) concentrations before and after the treatment in patients receiving ESA (left) and HIF-PHIs (right). (B) Changes in MCV, mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) before and after the treatment in patients receiving ESA (left) and HIF-PHIs (right). (C) Association of changes in Hb levels (ΔHb) with changes in MCV (ΔMCV) before and after the treatment in patients receiving ESA. (D) Association of changes in Hb levels (ΔHb) with changes in MCV (ΔMCV) before and after the treatment in patients receiving HIF-PHIs. Data are expressed as mean ± SD
Fig. 2
Fig. 2
Logistic regression analysis in the study participants based on anti-anemic treatments and baseline MCV values (A and B) Odds ratio for anemia improvement (defined as the increase in Hb levels) in patients receiving ESA and HIF-PHIs based on the mean value (90.9 fL) of MCV reference range. (A) In model 1, age, sex, smoking status, alcohol use, and eGFR were included as the explanatory valuables. (B) In model 2, diabetes and heart diseases were included in addition to the explanatory valuables in model 1
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