Use of molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, in chronic kidney disease-associated anemia in cats

J Vet Intern Med. 2024 Jan-Feb;38(1):197-204. doi: 10.1111/jvim.16807. Epub 2023 Sep 22.

Abstract

Background: Erythropoietic effects of molidustat, a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, were previously demonstrated in healthy cats.

Objective: To evaluate the safety and erythropoietic effects of daily PO administration of molidustat in anemic cats with chronic kidney disease (CKD).

Animals: Twenty-one client-owned CKD cats (4-17 years old) with anemia.

Methods: Multicenter field study; randomized, masked, and placebo-controlled. Cats were treated PO once daily for 28 days with suspensions of control product (CP; n = 6) or 5 mg/kg of molidustat (n = 15). Hematocrit (HCT) was evaluated at weekly intervals. Individual cat treatment success was defined as a ≥4% point increase in HCT compared to baseline.

Results: Control group mean HCT remained low throughout the study (20.1%-23.4%). Mean HCT of molidustat-treated cats increased weekly, and a significant increase compared to baseline (23.6%) was first observed on Day 21 (27.3%; P < .001; 95% confidence interval [CI], 1.69-5.67). Compared to CP group, mean HCT was significantly higher on Day 21 (27.3% vs 20.1%; P < .001; 95% CI, 2.91-10.75) but not significantly higher on Day 28 (27.8% vs 23.4%; P = .06; 95% CI, -0.23 to 9.88). The number of individual treatment successes on Day 28 was higher among remaining molidustat-treated cats (7/14) compared to remaining control cats (1/5), but there was no significant difference between groups.

Conclusions and clinical importance: Daily PO molidustat administration may stimulate a clinically relevant erythropoietic response in anemic cats with CKD. This HIF-PH inhibitor may be an alternative for managing anemia in cats compared to recombinant EPO treatment.

Keywords: PCV; anemic; erythropoietin; hematocrit; nonregenerative; renal.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial, Veterinary

MeSH terms

  • Anemia* / drug therapy
  • Anemia* / etiology
  • Anemia* / veterinary
  • Animals
  • Cat Diseases* / drug therapy
  • Cats
  • Hypoxia / veterinary
  • Hypoxia-Inducible Factor-Proline Dioxygenases / antagonists & inhibitors
  • Hypoxia-Inducible Factor-Proline Dioxygenases / therapeutic use
  • Prolyl Hydroxylases
  • Prolyl-Hydroxylase Inhibitors* / therapeutic use
  • Pyrazoles*
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / drug therapy
  • Renal Insufficiency, Chronic* / veterinary
  • Triazoles*

Substances

  • Hypoxia-Inducible Factor-Proline Dioxygenases
  • molidustat
  • Prolyl Hydroxylases
  • Prolyl-Hydroxylase Inhibitors
  • Pyrazoles
  • Triazoles

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