Desidustat: Role in management of anemia of chronic kidney disease (CKD)

Madhan

Clinical Pharmacist, Kauvery Hospital, Tennur, Trichy, Tamil Nadu

Introduction

Desidustat (ZYAN1) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that stimulates erythropoiesis. Stabilizing HIF via PHI is developing as a new therapeutic approach to treat anemia secondary to chronic kidney disease (CKD).

Anemia in CKD

Anemia of chronic kidney disease (CKD), is a form of normocytic, normochromic, hypo proliferative anemia [1]

The erythropoietic system is responsible for maintaining the balance in the supply of red blood cells, thus, ensuring an adequate tissue oxygenation, Hypoxia plays an important role in stimulating erythrocyte production through its interaction with the HIF (hypoxia-inducible factor) system; its degradation occurs in the absence of tissue hypoxia.

Erythropoietin produced mainly in the interstitial cells of the renal cortex, the half-life of erythropoietin is 5 – 12hrs, It binds to receptors of bone marrow cells to produce erythrocytes.

Although the reduction in the production of erythropoietin significantly contributes to anemia in CKD, it is not the only cause, iron deficiency is common, and it is estimated that patients on hemodialysisi have an iron loss of around 1 – 3gram per year, even in patient not receiving dialysis.

Anemia exists when Hb falls below 13 g/dl in males and 12 g/dl in females. Anemia is a common complication associated with chronic kidney disease as renal parenchyma undergoes progressive damage and generation of Erythropoietin fails

Anaemia affects over 50% of advanced chronic kidney disease (CKD) patients, increasing cardiovascular mortality. Traditional erythropoiesis-stimulating agents (ESAs) require injections and carry risks, such as hypertension and thromboembolism. Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs), including desidustat, roxadustat, and molidustat, offer oral alternatives by stabilising HIF-α mimicking hypoxia to enhance erythropoietin production and improve iron metabolism 2

Methodology

It is a prospective observational study

Baseline characteristics of patients:

In this project, all are patients with CKD and have CKD induced anemia. The study examined whether Desidustat increased hemoglobin(Hb) and red blood cell(RBC) levels in patients.

Treatment management protocol

Iron therapy

Non dialysis – If tolerated try oral iron first
On dialysis – IV iron

ESA therapy

Starting dose of epoetin alpha 50-100 IU/kg 3*/week

Non dialysis – Use subcutaneously
On dialysis – IV route

Starting dose of darbepoetin is 0.75mcg/kg every 2weeks subcutaneously.

HIF-PH inhibitors(Desidustat)

Non dialysis – The starting dose id 100mg orally, three times a week, patient switching from ESA the starting dose is 100, 125 or 150mg three times a week depending on prior ESA dose.

On dialysis dependent CKD also start with 100mg three times weekly, ESA experienced dialysis patients may start with 100-150mg three times weekly.

Efficacy outcome

In the project, it was observed that desidustat increased hemoglobin(HB) and red blood cell(RBC) levels in patients, with efficacy comparable to that of injectable erythropoietin. Howevr, patient preferred the oral route due to its greater convenience and ease of administration compared to injectable.

In this project, data from 9 CKD induced anemia patient were analyzed.

Following desidustat treatment

Hemoglobin levels increased by an average of 23.30%
Red blood cell count increased by an average of 21.44%.

Parameter	Pt-1	Pt-2	Pt-3	Pt-4	Pt-5	Pt-6	Pt-7	Pt-8	Pt-9
Pre HB	6.7	9	8.8	8.4	9.1	6.5	5.7	9.9	8.5
Post HB	6.9	10	11.9	9.3	14.3	9.1	7.5	11.5	9.1

Parameter	Pt-1	Pt-2	Pt-3	Pt-4	Pt-5	Pt-6	Pt-7	Pt-8	Pt-9
Pre RBC	2.31	3.16	3.46	3.42	3.17	2.15	2.01	3.09	3.14
Post RBC	2.36	3.58	4.54	3.54	4.48	3.11	2.89	3.46	3.3

Comparative outcomes

Renocrit (Erythropoietin)

2000IU – Rs. 615
4000IU – Rs. 1304
10000IU – Rs.2243

Renocrit therapy cost increased with dosage and may require multiple doses per week depending on the patient need

Desidustat

Oxemia 50mg – Rs.100/Tab
Rystat 50mg – Rs.110/Tab
Rystat 100mg – Rs.241/Tab

While daily oral dosing may lead to a higher cumulative monthly cost, it eliminates cost related to injection administration and monitoring

Conclusion

In this comparative analysis of injectable erythrpoietin and oral HIF for the treatment of anemia in CKD patient.

Desidustat present a clinically effective and patient friendly alternative to Erythropoietin for managing anemia in CKD patient although cost difference exist the oral administration and comparable efficacy makes desidustat viable and often preferred option, particularly in outpatient and home based care settings.

Reference

Kaandeeban Mohanraj, Cheryl Singla, Vidhya Mohanraj, Vishnuvardan Venkatramanan, Redefining anaemia management in CKD: comparative insights on desidustat, roxadustat, and molidustat as oral HIF-PH inhibitors, ClinicalMedicine, Volume25, Issue4, Supplement,2025,100451.
Sharma S, Sood A, Rana A, Sawaraj S. Comparison of safety and efficacy of desidustat with erythropoietin in newly diagnosed patient of anemia in chronic kidney disease: a prospective, open label, randomized controlled trial. Int J Basic Clin Pharmacol 2025; 14:499-507.

Desidustat: Role in management of anemia of chronic kidney disease (CKD)

Desidustat: Role in management of anemia of chronic kidney disease (CKD)

Madhan

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