Adherence to monitoring iron indices at the initiation of erythropoiesis-stimulating agents or hypoxia-inducible factor prolyl hydroxylase inhibitors

TL;DR

This study examines how well healthcare facilities in Japan follow guidelines for monitoring iron levels when starting anemia treatments for kidney disease patients.

Contribution

The study provides real-world evidence on adherence to iron monitoring guidelines for HIF-PH inhibitors and ESAs in Japan.

Findings

Testing rates for iron indices were below 60% across all measured parameters.

University and DPC-affiliated hospitals showed significantly higher adherence to testing guidelines.

Adherence varied significantly by facility type, with clinics showing the lowest adherence.

Abstract

Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors have been used for the treatment of anemia in patients with chronic kidney disease not receiving dialysis since 2020. In September 2020, the Japanese Society of Nephrology published recommendations for the appropriate use of HIF-PH inhibitors, which emphasized monitoring iron indices. However, real-world adherence to these recommendations remains unclear.

We retrieved the data of new users of erythropoietin-stimulating agents (ESAs) or HIF-PH inhibitors from a large Japanese claims database (DeSC, Tokyo, Japan) between 2018 and 2022. Adherence to iron testing before and after the treatments was analyzed using modified Poisson regression and Cox models. Facility-level variations were assessed via mixed-effects models.

We identified 105,346 patients who had a new prescription of ESAs (n = 86,263) or HIF-PH inhibitors (n = 19,083) and did not have kidney failure with replacement therapy. The proportion of HIF-PH inhibitor use increased from 3.6% in 2020 to 42.7% in 2022. During the study period, testing frequency for serum iron, serum TIBC or UIBC, and ferritin ranged from 57.2–59.8%, 39.2–42.8%, and 50.6–52.6%, respectively. Multivariate analysis showed that adherence to testing was significantly higher in university hospitals, Diagnosis Procedure Combination-affiliated DPC hospitals, and non-DPC hospitals compared with clinics. A similar tendency was observed in testing after the index date.

The type of facility was the primary determinant of adherence to the recommendation for iron indices testing before the initiation of ESAs or HIF-PH inhibitors. Targeted educational interventions in low-adherence settings may help improve adherence rates and optimize patient care.

The online version contains supplementary material available at 10.1007/s10157-025-02761-1.