Comparative Evaluation of Desidustat Versus Erythropoietin on Hemoglobin Correction, Iron Utilisation and Cost in Dialysis-Dependent CKD Patients: A 12-Month Randomized Controlled Study

Anemia is a common, debilitating complication of chronic kidney disease (CKD) that substantially worsens morbidity, cardiovascular risk. Although erythropoiesis-stimulating agents (ESAs) remain effective, their drawbacks include adverse effects, high cost, and the need for parenteral dosing. Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs), such as desidustat, provide a novel oral alternative by enhancing endogenous erythropoietin synthesis and improving iron utilisation. This randomised trial assesses the efficacy, safety, and direct medical cost of HIF-PHI (desidustat) versus ESA (erythropoietin) therapy in patients with dialysis-dependent CKD (DD-CKD).

A prospective, randomized, open-label comparative study was conducted in 104 adult DD-CKD patients over 12 months. Adults (18–75 years) with CKD-DD and anemia on maintenance hemodialysis for ≥3 months were enrolled. Exclusion criteria included inability to consent or complete interviews, psychiatric illness, malignancy, active/recent blood loss, pregnancy, breastfeeding, or participation in another drug trial. Patients were randomly assigned (1:1) to receive oral desidustat (n=52) thrice weekly or subcutaneous erythropoietin (EPO; n=52) per standard dosing. All received iron, vitamin B12, and folate supplements as needed. Effectiveness was assessed by changes in hemoglobin and iron indices (iron, TIBC, TSAT, ferritin, hepcidin, sTfR). Safety, treatment-emergent adverse events (TEAEs), and mortality were monitored. Cost analysis covered direct medical costs, including drugs. Statistical analyses used SPSS v28 and JMP 18.2. Within-group changes were analyzed via repeated-measures ANOVA; between-group comparisons used independent t-tests. p < 0.05 was considered statistically significant.

Of the 104 enrolled patients (52 per arm), 84 (80.8 %) completed the 12-month follow-up (per-protocol). Participants had a mean age of 53.9 ± 11.8 years; 67.3 % were male, and 60.6 % fell into the lower socioeconomic category. Baseline haemoglobin (Hb) and iron-profile variables were balanced between the Desidustat and Erythropoietin (EPO) arms. By month 12, both treatment groups had a statistically significant rise in mean Hb versus baseline (p < 0.05). However, no significant difference in Hb levels was observed between Desidustat and EPO recipients at 12 months. Transferrin-saturation (TSAT) rose significantly in the Desidustat arm but remained unchanged with EPO. Ferritin declined markedly in both groups, reflecting mobilised iron stores. Declines in hepcidin and normalisation of soluble transferrin receptor (sTfR) were more marked with Desidustat, indicating improved erythropoietic efficiency. No clinically meaningful hepatic or metabolic abnormalities were observed. The most frequent treatment-emergent adverse events (TEAEs) were mild hypertension (13.5 %) and arthralgia (8.7 %). Mortality was 3.8 % in the Desidustat arm and 5.7 % in the EPO arm. In the health-economic analysis across all dialysis schedules and dialyser types, the annual medication cost was ₹ 76,024 for the Desidustat group versus ₹ 84,840 for the EPO group, yielding an 11.6 % cost reduction though this difference did not reach statistical significance.

Desidustat demonstrated superior hemoglobin correction, better iron utilisation and lower annual treatment cost compared to Erythropoietin, with comparable safety in DD-CKD. The oral HIF-PHD inhibitor thus represents an effective, patient-convenient, and economically favourable alternative to injectable ESA therapy for renal anemia management in real-world Indian settings.