Comparing the Efficacy of Desidustat Versus Erythropoietin in the Management of Anemia in Patients With Dialysis-Naïve Chronic Kidney Disease: A Randomized Open-Label Trial.

BACKGROUND

Anemia is a serious complication of chronic kidney disease (CKD). The current standard of care for anemia of CKD is erythropoiesis-stimulating agents (ESAs). However, ESAs have several limitations, such as compliance issues, high cost, cardiovascular risks, and potential immunogenicity. Desidustat is a novel oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that enhances endogenous erythropoietin synthesis and iron utilization.

METHODS

This open-label, randomized, prospective, non-inferiority trial included 60 dialysis-naïve CKD patients with baseline hemoglobin of ≤9 g/dL and adequate iron stores who were randomized (1:1) to receive either desidustat orally or erythropoietin subcutaneous injection for six months, once every two weeks.

RESULTS

Desidustat showed non-inferiority to erythropoietin in increasing and maintaining hemoglobin levels within the target range over six months. The mean hemoglobin increased in the desidustat arm from baseline 7.99±0.73 to the estimated marginal mean (EMM) of 10.01±0.21 (95% CI: 9.59-10.4), while the mean hemoglobin in the erythropoietin arm increased from baseline 7.68±0.84 to the EMM of 9.89±0.21 g/dL (95% CI: 9.46-10.3). The percentage of hemoglobin responders was higher with desidustat (15 (57.69%)) compared to erythropoietin (12 (48%)). Both treatments showed comparable improvements in hematological parameters and iron profiles. Desidustat had a greater improvement in quality of life score (Chronic Kidney Disease-Anemia Questionnaire (CKD-AQ) compared to erythropoietin at each time interval, reflecting lower symptom burden. From baseline to six months, an increased level of growth differentiation factor-15 (GDF-15) and a decreased level of interleukin 6 (IL-6) were noted in both arms. No correlation was found between hemoglobin difference, biochemical parameters, and biomarkers.

CONCLUSION

Desidustat was non-inferior to erythropoietin in treating anemia of dialysis-naïve CKD patients. Desidustat offers a safe and effective alternative to ESAs with better compliance.