Introduction:
Functional iron deficiency is a common complication in CKD patients. It is mainly due to chronic inflammation causing hepcidin upregulation, which inhibits Gut absorption of iron as well as inhibits release of iron from its stored pool in reticuloendothelial system and macrophages. Current approach for managing functional iron deficiency is to bypass GI absorption by I/V dosing of freely available iron with targeting higher levels of ferritin in comparison to absolute iron deficiency, but this approach does not address iron sequestration.
Ill effects of functional Iron deficiency and iron sequestration increase the oxidative stress, cardiovascular risk, contribute to cognitive decline, malnutrition, impaired wound healing, and increased risk of infection.
Desidustat is a Hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) , which by stabilizing HIF increases endogenous erythropoietin secretion & suppresses hepcidin.
In this study, we have used a novel agent (Desidustat) and compared it with standard of care in correcting iron sequestration and functional iron deficiency.
Methods:
This was a multi-center retrospective cohort study. Data was collected for period of May 2023 to August 2024 . This study included adults, (age > 18 years) who were Diagnosed as CKD-5D with Anemia and was on maintenance dialysis with dialysis vintage of > 3 month and have follow up data for at least 6 months. Patients with other etiology of anemia were excluded (GI bleed etc.). patients with at least 80 % of clinical and lab data were included.
Patients were divided into 2 groups – 1st group was Desidustat group (group size- 59)
2nd group was current standard practice i.e. erythropoietin (EPO) (group size – 154)
Both groups received I/V iron therapy in proactive based fashion till ferritin >700, TSat >40%. Patients were also on Vit B12 & folate supplement and other standard of care.
Dosing of erythropoietin was as per KDIGO. Desidustat was started at a dose of 100 mg thrice per week and titrated as per hemoglobin
Patients were on monthly monitoring of Hemoglobin. Ferritin & T sat were done at baseline and 3 monthly. Other labs as per standard of care.
Groups were compared using Mann-Whitney U test for difference in hemoglobin & iron status (baseline, 6 months, and change from baseline.)
Results:
The baseline characteristics were comparable between the two group. There was no significant difference in the hemoglobin, ferritin and T sat at baseline.
There was no significant difference the rise of hemoglobin between the two groups. (Desidustat – 3 gram over 6 months vs 2.8 gram in EPO group)
There was Significant difference in ferritin levels at 6 months in the both groups. Ferritin (380 µg/L in desidustat group with 58 µg/L decreases from baseline vs 558 µg/L in EPO group, with 110 µg/L rises from baseline)
while T sat level were comparable (T sat 30 % in desidustat group, 6% rise from baseline vs 33% in EPO group, 7 % rise from baseline)
Conclusions:
This retrospective cohort study demonstrate that Desidustat achieves desired hemoglobin levels with significantly less iron sequestration in comparison to EPO group in patients of CKD 5-D with anemia.
Patient receiving desidustat may be switched to I/V iron given in a reactive fashion as it will be more cost effective as well as avoid long term oxidative stress of iron sequestration while also avoiding the ill effects of supraphysiological exogenous erythropoietin.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.