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

Tetsushi Tezuka; Hiroyuki Arakawa; Kai Kudo; Hideyuki Takehara; Masanobu Morioka; Kazutaka Ikeda; Takashi Ikeda; Keisuke Yasuda; Yuko Fujima; Motoo Kobayashi; Yuki Okada; Toshiro Arai; Satoko Arai; Toru Miyazaki

doi:10.1016/j.tvjl.2026.106545

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

Vet J. 2026 Jan 3:315:106545. doi: 10.1016/j.tvjl.2026.106545. Online ahead of print.

Authors

Tetsushi Tezuka¹, Hiroyuki Arakawa², Kai Kudo³, Hideyuki Takehara⁴, Masanobu Morioka⁴, Kazutaka Ikeda⁵, Takashi Ikeda⁶, Keisuke Yasuda³, Yuko Fujima⁷, Motoo Kobayashi⁸, Yuki Okada⁹, Toshiro Arai¹⁰, Satoko Arai¹¹, Toru Miyazaki¹²

Affiliations

¹ The Institute for AIM Medicine (IAM), Tokyo 162-8666, Japan; Takashimadaira Tezuka Animal Hospital, Tokyo 175-0082, Japan; Elmer Animal Clinic, Tokyo 177-0032, Japan.
² Elms-united Innovation Institute, Tokyo 108-0074, Japan.
³ The Institute for AIM Medicine (IAM), Tokyo 162-8666, Japan.
⁴ Takehara Veterinary Hospital, Kawasaki 210-0012, Japan.
⁵ Department of Applied Genomics, Laboratory of Biomolecule Analysis, Kazusa DNA Research Institute, Chiba 292-0818, Japan.
⁶ The Institute for AIM Medicine (IAM), Tokyo 162-8666, Japan; Department of Urology, Tokyo Women's Medical University, Tokyo 162-8666, Japan.
⁷ Elms-united Animal Hospital Group, Tokyo 108-0074, Japan.
⁸ Seijo Kobayashi Veterinary Clinic, Tokyo 157-0066, Japan.
⁹ Seven Hills Veterinary Hospital. San Francisco, CA 94131, USA.
¹⁰ Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.
¹¹ The Institute for AIM Medicine (IAM), Tokyo 162-8666, Japan. Electronic address: arai.satoko@iamaim.jp.
¹² The Institute for AIM Medicine (IAM), Tokyo 162-8666, Japan; LEAP, Japan Agency for Medical Research and Development, Tokyo 113-0033, Japan; Laboratoire d'ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, Institut National de la Santé et de la Recherche Médicale UMR_S 1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg, Laboratory of Excellence TRANSPLANTEX, Université de Strasbourg, Strasbourg, France. Electronic address: tm@iamaim.jp.

PMID: 41485732
DOI: 10.1016/j.tvjl.2026.106545

Abstract

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.

Keywords: indoxyl sulfate; mass spectrometry; prognosis; sphingolipid; uremia.