A clinical impact of apoptosis inhibitor of macrophage on feline chronic kidney disease

Cats are highly susceptible to chronic kidney disease (CKD), for which effective treatments remain unavailable. We previously reported a genetic deficiency in activating apoptosis inhibitor of macrophages (AIM) in cats. Based on a hypothesis that the deficiency in AIM activation may contribute to the high susceptibility of cats to CKD, we investigated clinical impacts of recombinant AIM (rAIM) treatment in cats with advanced CKD, as an exploratory, non-pivotal study. 216 CKD cats were screened and those harboring serum creatinine concentrations between 2.9 and 5.0 mg/dL, including 26 with ≥ 5 µg/mL serum indoxyl sulfate (IS) concentrations and 9 with < 5 μg/mL IS, were enrolled into the study. Of the 26 cats, 6 received mouse rAIM administrations, 5 received feline rAIM, and 15 served as non-treated controls. Their survival was monitored for 360 days, and kidney biomarkers, metabolomic profiles, as well as sphingolipids in serum were assessed. The median survival time of non-treated controls was 167 days (95% confidence interval [CI]: 116–217), whereas rAIM treatment significantly extended survival, with a cumulative survival rate of 0.83 (95% CI: 0.53–1.0) at 360 days by mouse rAIM and 0.8 (95% CI: 0.44–1.0) by feline rAIM compared to 0.20 (95% CI: 0.0–0.40) in controls. Additionally, rAIM prevented the worsening of kidney biomarkers and uremic toxins, restoring serum sphingomyelins that reduce inflammation and fibrosis. The 9 cats with lower IS concentrations showed 100% survival at 360 days without rAIM treatment. These findings support the use of AIM-based therapies against advanced CKD in cats. • Intravenous administrations of recombinant AIM significantly extend survival of cats with advanced CKD • rAIM treatment prevents progression to end-stage CKD and halted the worsening of kidney biomarkers in cats • rAIM treatment prevents augmentation of serum toxic metabolites in cats with advanced CKD • rAIM treatment restores anti-inflammatory and anti-fibrotic sphingomyelins in serum • Serum indoxyl sulfate concentration is a valuable biomarker for diagnosing CKD in cats at high risk of approaching IRIS stage 4