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

Abstract

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

• anemic
• erythropoietin
• hematocrit
• nonregenerative
• PCV
• renal