Apoptosis Inhibitor of Macrophages in Cats: A Potential Link Between an Exon 3 Variant Allele and Progression of Naturally Occurring Chronic Kidney Disease

ABSTRACT Background The protein apoptosis inhibitor of macrophages (AIM) is involved in kidney repair. An AIM (fAIM) genetic variant in cats resulting in a domain duplication might abrogate fAIM's protective effect on kidney function. Objectives To confirm that the domain duplication previously...

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Main Authors: Gabriela C. L. Evangelista, Julianne K. Hwang, Liam E. Broughton‐Neiswanger, Emily C. Carlo Reis, Michael H. Court, Katrina A. Mealey, Nicolas F. Villarino
Format: Article
Language:English
Published: Wiley 2025-07-01
Series:Journal of Veterinary Internal Medicine
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Online Access:https://doi.org/10.1111/jvim.70136
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author Gabriela C. L. Evangelista
Julianne K. Hwang
Liam E. Broughton‐Neiswanger
Emily C. Carlo Reis
Michael H. Court
Katrina A. Mealey
Nicolas F. Villarino
author_facet Gabriela C. L. Evangelista
Julianne K. Hwang
Liam E. Broughton‐Neiswanger
Emily C. Carlo Reis
Michael H. Court
Katrina A. Mealey
Nicolas F. Villarino
author_sort Gabriela C. L. Evangelista
collection DOAJ
description ABSTRACT Background The protein apoptosis inhibitor of macrophages (AIM) is involved in kidney repair. An AIM (fAIM) genetic variant in cats resulting in a domain duplication might abrogate fAIM's protective effect on kidney function. Objectives To confirm that the domain duplication previously described in fAIM results from an exon duplication at the genomic level and to determine if cats with chronic kidney disease (CKD) harboring the variant fAIM allele are at higher risk for a decline in renal function relative to fAIM wild‐type cats. Animals Medical records (n = 172) and genomic DNA samples (n = 100) from cats presented to Washington State University and having a diagnosis of CKD were analyzed. Methods Sequencing and PCR were used to determine fAIM genotype. Based on serum creatinine (SCr) concentrations, cats were phenotyped according to IRIS CKD staging. The phenotype–genotype association was tested using Fisher's exact test. Results The 4‐domain variant of fAIM was confirmed to be a result of exon 3 duplication and is present in 62% of the DNA samples from cats. Medical records of cats (n = 50) with CKD met the inclusion criteria. Cats homozygous for the exon 3 fAIM variant allele are more likely to have worse IRIS stage (p = 0.01) and more likely to have experienced renal function deterioration (increasing SCr concentration) than fAIM wild‐type cats (p = 0.03). Conclusions and Clinical Importance The fAIM homozygous variant genotype is associated with declining kidney function in cats with CKD, presumably from deficient fAIM‐mediated renal tubular repair.
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spelling doaj-art-4ba82641c5b5441ea08ca835cfa676c82025-08-20T03:56:09ZengWileyJournal of Veterinary Internal Medicine0891-66401939-16762025-07-01394n/an/a10.1111/jvim.70136Apoptosis Inhibitor of Macrophages in Cats: A Potential Link Between an Exon 3 Variant Allele and Progression of Naturally Occurring Chronic Kidney DiseaseGabriela C. L. Evangelista0Julianne K. Hwang1Liam E. Broughton‐Neiswanger2Emily C. Carlo Reis3Michael H. Court4Katrina A. Mealey5Nicolas F. Villarino6Veterinary Department Federal University of Viçosa Viçosa BrazilDepartment of Veterinary Clinical Sciences College of Veterinary Medicine Washington State University Pullman Washington USADepartment of Veterinary Microbiology and Pathology, College of Veterinary Medicine Washington State University Pullman Washington USAVeterinary Department Federal University of Viçosa Viçosa BrazilProgram of Individualized Medicine, Department of Veterinary Clinical Sciences College of Veterinary Medicine Washington State University Pullman Washington USAProgram of Individualized Medicine, Department of Veterinary Clinical Sciences College of Veterinary Medicine Washington State University Pullman Washington USAProgram of Individualized Medicine, Department of Veterinary Clinical Sciences College of Veterinary Medicine Washington State University Pullman Washington USAABSTRACT Background The protein apoptosis inhibitor of macrophages (AIM) is involved in kidney repair. An AIM (fAIM) genetic variant in cats resulting in a domain duplication might abrogate fAIM's protective effect on kidney function. Objectives To confirm that the domain duplication previously described in fAIM results from an exon duplication at the genomic level and to determine if cats with chronic kidney disease (CKD) harboring the variant fAIM allele are at higher risk for a decline in renal function relative to fAIM wild‐type cats. Animals Medical records (n = 172) and genomic DNA samples (n = 100) from cats presented to Washington State University and having a diagnosis of CKD were analyzed. Methods Sequencing and PCR were used to determine fAIM genotype. Based on serum creatinine (SCr) concentrations, cats were phenotyped according to IRIS CKD staging. The phenotype–genotype association was tested using Fisher's exact test. Results The 4‐domain variant of fAIM was confirmed to be a result of exon 3 duplication and is present in 62% of the DNA samples from cats. Medical records of cats (n = 50) with CKD met the inclusion criteria. Cats homozygous for the exon 3 fAIM variant allele are more likely to have worse IRIS stage (p = 0.01) and more likely to have experienced renal function deterioration (increasing SCr concentration) than fAIM wild‐type cats (p = 0.03). Conclusions and Clinical Importance The fAIM homozygous variant genotype is associated with declining kidney function in cats with CKD, presumably from deficient fAIM‐mediated renal tubular repair.https://doi.org/10.1111/jvim.70136biomarkercatsfAIMgeneticsrenal disease
spellingShingle Gabriela C. L. Evangelista
Julianne K. Hwang
Liam E. Broughton‐Neiswanger
Emily C. Carlo Reis
Michael H. Court
Katrina A. Mealey
Nicolas F. Villarino
Apoptosis Inhibitor of Macrophages in Cats: A Potential Link Between an Exon 3 Variant Allele and Progression of Naturally Occurring Chronic Kidney Disease
Journal of Veterinary Internal Medicine
biomarker
cats
fAIM
genetics
renal disease
title Apoptosis Inhibitor of Macrophages in Cats: A Potential Link Between an Exon 3 Variant Allele and Progression of Naturally Occurring Chronic Kidney Disease
title_full Apoptosis Inhibitor of Macrophages in Cats: A Potential Link Between an Exon 3 Variant Allele and Progression of Naturally Occurring Chronic Kidney Disease
title_fullStr Apoptosis Inhibitor of Macrophages in Cats: A Potential Link Between an Exon 3 Variant Allele and Progression of Naturally Occurring Chronic Kidney Disease
title_full_unstemmed Apoptosis Inhibitor of Macrophages in Cats: A Potential Link Between an Exon 3 Variant Allele and Progression of Naturally Occurring Chronic Kidney Disease
title_short Apoptosis Inhibitor of Macrophages in Cats: A Potential Link Between an Exon 3 Variant Allele and Progression of Naturally Occurring Chronic Kidney Disease
title_sort apoptosis inhibitor of macrophages in cats a potential link between an exon 3 variant allele and progression of naturally occurring chronic kidney disease
topic biomarker
cats
fAIM
genetics
renal disease
url https://doi.org/10.1111/jvim.70136
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