# Preservation of eGFRcre for 1 year with HIF-PHI in non-dialysis patients: a retrospective observational cohort study

## TL;DR

This study found that HIF-PHIs may better preserve kidney function than ESAs in non-dialysis patients with chronic kidney disease over one year.

## Contribution

The study provides new evidence on the renal protective effects of HIF-PHIs compared to ESAs in non-dialysis CKD patients.

## Key findings

- HIF-PHIs showed a slower decline in eGFRcre compared to ESAs (-2.11 vs. -3.27 mL/min/1.73 m² per year).
- The benefit of HIF-PHIs was most pronounced in CKD stage 4 patients (-1.89 vs. -3.69 mL/min/1.73 m² per year).

## Abstract

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) effectively increase hemoglobin levels to treat anemia in patients with chronic kidney disease (CKD). However, there is a paucity of studies on the effect of HIF-PHIs on renal outcomes, such as estimated glomerular filtration rate based on serum creatinine (eGFRcre). Therefore, this study aimed to examine the trajectory of eGFRcre decline following initiation of treatment with HIF-PHI and erythropoiesis-stimulating agents (ESAs) in non-dialysis patients.

This single-center, retrospective study enrolled non-dialysis patients who were prescribed HIF-PHIs between January 1, 2020 and December 31, 2022. We used five HIF-PHIs approved in Japan. The eGFRcre slope for a year after HIF-PHIs therapy was initiated was compared with that of ESAs. The eGFRcre slope was calculated using a linear mixed-effects model for repeated measures over a year from the time of enrollment.

This study included 134 patients: 79 and 55 patients treated with HIF-PHIs and ESAs, respectively. The model adjusting for time, drug (HIF-PHI or ESA), their interaction, age, sex, BMI, and CKD stage showed that the effect on eGFRcre differed between HIF-PHIs and ESAs (−2.11 ± 0.57 mL/min/1.73 m2 per year vs. −3.27 ± 0.17 mL/min/1.73 m2 per year, p = 0.046). Subgroup analysis by CKD stage revealed a difference in the eGFRcre slope between HIF-PHI and ESA only in the stage 4 group (−1.89 ± 0.44 mL/min/1.73 m2 per year vs. −3.69 ± 0.44 mL/min/1.73 m2 per year, p < 0.001).

HIF-PHI preserved eGFRcre for a year, suggesting that its effect was superior to that of ESA.

The online version contains supplementary material available at 10.1186/s40780-025-00527-1.