Roxadustat Maintains Anemia Control in Non-Dialyzed CKD Patients

Switching to roxadustat from erythropoiesis-stimulating agents (ESA) frequently results in Hb overshoot in patients with anemic, non-dialyzed chronic kidney disease (CKD).

The results from a recent 8-week retrospective pilot study have suggested roxadustat does not compromise anemia control in this group; however, investigators caution clinicians to be aware of the possibility of overshoot and emphasize the importance of early Hb level monitoring.1

Although ESA is considered the standard renal anemia treatment, it has been associated with poor patient prognosis in higher doses. Previous studies have attempted to define this connection, finding an association between both low hemoglobin levels and high-dose ESA therapy and all-cause mortality. These studies also indicated an interaction between ESA dosage and hemoglobin level on all-cause mortality.2

Roxadustat has demonstrated noninferiority to various anemia treatments in previous trials, such as DOLOMITES. However, a general increase in Hb levels was noted during these trials with little mention of the observation. This retrospective study was conducted to determine the frequency of this overshoot.1

“Because maintaining higher Hb levels and a rapid increase in the Hb levels are risk factors for poor outcomes, clinicians should be aware of Hb overshoot caused my roxadustat in the early weeks, but this has not yet been studied extensively,” wrote Masanori Tamaki, department of nephrology, Tokushima University Hospital, and colleagues. “Additionally, real-world data on switching treatment from ESA to roxadustat in non-dialyzed patients with CKD is limited.”1

Tamaki and colleagues collected data on patients with anemia and non-dialyzed CKD who switched from ESA to roxadustat or continued ESA from 2 hospitals in Japan. Inclusion criteria were as follows:

• ≥20 years of age
• Baseline estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2
• Baseline Hb level ≤12.5 g/dL
• Patients who had started on epoetin beta pegol or darbepoetin ≥2 months prior to switch
• Last administration of epoetin beta pegol ≥4 weeks ago or darbepoetin ≥2 weeks ago
• Patients who wished to switch from ESA to roxadustat

Exclusion criteria included proliferative diabetic retinopathy, a history of cancer or thrombosis, severe hypertension, or hyperkalemia at baseline (≥6.0 mEq/L). These inclusion and exclusion criteria were the same for patients continuing ESA and those switching to roxadustat.1

Patients who developed Hb levels >12.5 g/dL after beginning observation were considered patients with Hb overshoot, according to ruxadostat product information. Patients who had Hb overshoot had treatment discontinued and visited the hospital 4 weeks after discontinuation.1

A total of 23 patients switched from ESA to roxadustat, and 63 continued with ESA in this study. Investigators measured mean baseline Hb level at 10.77 g/dL for the roxadustat group and 10.64 g/dL for the ESA group. Median eGFR was 15.7 mL/min/1.73m2 and 15.2 mL/min/1.73 m2, respectively.1

Within the 8-week trial period, 34.8% (n = 8) of patients in the roxadustat group and 3.2% (n = 2) in the ESA group exhibited Hb overshoot. Critical Hb level elevation of >13 g/dL was observed in 2 patients in the roxadustat group and none in ESA. The odds ratio for overshoot between both groups was 20 (95% CI, 3.77-106; P <.01) – after adjusting for age, sex, body mass index, Hb levels, and other variables, the ratio was 20.2 (95% CI, 3.13-130; P <.01).1

Patients who developed Hb overshoot demonstrated higher median reticulocyte counts and relatively lower ferritin and transferrin saturation levels. Later analysis indicated a significant relationship between ΔHb levels and HDL-C. After controlling for several factors, the significance was retained.1

Although these results largely indicate the efficacy and safety of switching to roxadustat, Tamaki and colleagues still caution clinicians to heavily monitor for Hb overshoot, particularly in patients switching from ESAs.1

“Our findings suggest a therapeutic shift from ESA to roxadustat. Caution is warranted, especially in younger patients with higher baseline Hb or Ht levels, as they may not be ideal candidates for this switch,” wrote Tamaki and colleagues. “Further large-scale studies are needed to validate this therapeutic strategy.”1

References

1. Tamaki M, Inagaki T, Minato M, et al. Roxadustat for Treating Anemia in Patients with Advanced Chronic Kidney Disease Not Undergoing Dialysis: A Retrospective Study. Intern Med. 2025;64(9):1303-1314. doi:10.2169/internalmedicine.3773-24

2. Fukuma S, Yamaguchi T, Hashimoto S, et al. Erythropoiesis-stimulating agent responsiveness and mortality in hemodialysis patients: results from a cohort study from the dialysis registry in Japan. Am J Kidney Dis. 2012;59(1):108-116. doi:10.1053/j.ajkd.2011.07.014