ORAL TREATEMENT FOR ANEMIA IN CHRONIC KIDNEY DISEASE

https://meditropics.com/1366-2/

*Harshita Choudhary,

*Post-graduate Resident, Department Of Medicine, LHMC New Delhi

INTRODUCTION

Treatment of Anemia in chronic kidney disease (CKD) has been mainly dependent on Injectible Iron and Erythropoetin stimulating agents (ESA) like darbopoetin-alfa and erythropoietin alpha, which are parenteral drugs. This has been revolutionized with introduction of novel class of drugs like Daprudostat  (approved in 2023) and Vadadustat (approved in 2024) which are  hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor((PHI),  taken orally.

MECHANISM OF ACTION

Oxygen-dependent inhibition of HIF-prolyl hydroxylase enzymes by these molecules leads to the buildup of HIF-α, which in turn increases the expression of genes responsive to HIF, such as EPO and those related to iron metabolism and utilization. It would increase the endogenous production of erythropoietin, decreases hepcidin levels in circulation, and ultimately promotes higher levels of red blood cell production and increased hemoglobin concentrations in patients with End Stage Renal disease. (1)

INDICATION

Dapadustat is indicated for treatment of anemia due to chronic kidney disease (CKD) in adults on dialysis for ≥4 months (2)

DOSING

Available as Jesduvroq (by GSK)

  1. Dosing in patients not treated with an erythropoietin-stimulating agent (ESA): Starting dose is based on pretreatment hemoglobin level

i)Hb<9 g/dL: Start at 4 mg PO qDay

ii)Hb 9-10 g/dL: Start at 2 mg PO qDay

iii)Hb >10 g/dL: Start at 1 mg PO qDay

  1. Switching from an ESA: Starting dose is based on dosing regimen of ESA at time of substitution

DOSING CONSIDERATIONS

  • Monitoring response to therapy: Following initiation and after each dose adjustment, monitor Hb q2Weeks for first month and then q4Weeks thereafter
  • Anemia or iron status:
    • Correct and exclude other causes of anemia
    • Serum ferritin <100 mcg/mL or serum transferrin saturation <20%: Administer supplemental iron therapy
  • Liver function testing

 

ADVERSE EFFECTS

  • Increased Risk of Death, Myocardial Infarction, Stroke, Venous Thromboembolism, and
  • Thrombosis of Vascular Access
  • Risk of Hospitalization for Heart Failure
  • Hypertension
  • Gastrointestinal Erosion

REFERENCES:

  1. Haider MU, Furqan M, Mehmood Q. Daprodustat: A potential game-changer in renal anemia therapy-A perspective. Front Pharmacol. 2023;14:1249492.
  2. Fadlalmola HA, Al-Sayaghi KM, Al-Hebshi AA, Alhujaily M, Alyamani AO, Alem AA, Syrafi MH, Alem S, Farhat AH, Mohamed FA, Abdalrahman HH. Efficacy of daprodustat for patients on dialysis with anemia: systematic review and network meta-analysis. Pan Afr. med. j.2024;47.