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

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.