image: Figure 4. Organic anionic transporter RNA-seq gene expressions. Medullar (A–D) and cortical (E–H) tissue expressions of OAT4, OAT1, OAPT4C1, and ABCC2, respectively. Illustration of transporters in the proximal tubule cell (I). OAT1 and OATP4C1 are the uptake transporters on the basolateral surface, while ABCC2 is the efflux transporter localized at the apical surface. OAT4 is thought to play a role in both reabsorption and secretion from the apical side. All genes were differentially expressed between control and across CKD groups in both cortex and medullar (FDR<0.1 in all cases). Bars indicate means. Asterisks indicate Dunn’s multiple comparisons tests: *P<0.05, **P<0.01. OAT1/4, organic anion transporter family member 1/4; OATP4C1, organic anion transporting peptide family member 4C1; ABCC2, ATP-binding cassette subfamily C member 2. CKD1/2: CKD stages 1 and 2; CKD3/4: CKD stages 3 and 4; Amyloid: CKD by amyloidosis. Panel I created with BioRender.com.
Credit: Copyright: © 2024 Li et al.
“Cats and humans share 90.9%, 77.8%, and 82.5% identities in OAT1, OATP4C1, and ABCC2 proteins, respectively.”
BUFFALO, NY- January 28, 2025 – A new research paper was published in Volume 16, Issue 22 of Aging (Aging-US) on December 20, 2024, titled, “Impaired renal transporter gene expression and uremic toxin excretion as aging hallmarks in cats with naturally occurring chronic kidney disease.”
This study, led by researchers Qinghong Li, James A. Holzwarth, Bethany Smith, Sonia Karaz, Mathieu Membrez, Vincenzo Sorrentino, Stacie Summers, Julie Spears, and Eugenia Migliavacca from Nestlé Purina Research and Oregon State University, explores how aging affects kidney function in cats with chronic kidney disease (CKD). The researchers found that older cats have lower levels of important kidney transporter genes, which usually help remove harmful waste products from the blood. These findings could help veterinarians better understand CKD in aging cats and offer insights that may be relevant to human kidney health.
“Chronic kidney disease (CKD) is a naturally occurring kidney disease common in both geriatric cats and older people. Despite differing etiology, both species share many pathophysiological similarities, including chronic tubulointerstitial inflammation and fibrosis.”
Older cats with CKD struggle to filter toxins from their bloodstream effectively. In this study, the researchers analyzed kidney samples from two cat cohorts aged 6 to 21 years. The cohort number one included 41 colony cats: 28 control and 13 CKD cats. The cohort number two had 30 privately owned cats with 10 control and 20 CKD cats. They discovered that certain transporter genes, such as OAT1, OAT4, OATP4C1 and ABCC2, were significantly decreased in cats with CKD compared to healthy cats. The research team also found increased levels of harmful toxins in the blood of cats with CKD. Even healthy older cats had higher toxin levels compared to younger cats, showing that aging itself might contribute to declining kidney function.
Monitoring kidney transporters levels and toxin buildup may help detect the disease early and improve treatment options. The researchers highlight the importance of regular veterinary check-ups to catch kidney problems early and keep cats healthier for longer.
Because cats and humans share similar kidney health challenges, studying feline CKD can provide valuable insights into human kidney disease and aging. Continued research is essential to develop treatments that may improve kidney function in aging cats and potentially benefit humans as well.
Read the full paper: DOI: https://doi.org/10.18632/aging.206176
Corresponding authors: Qinghong Li – qinghong.li@rd.nestle.com
Keywords: aging, trimethylamine N-oxide, indoxyl sulfate, OAT1, OATP4C1, ABCC2
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About Aging:
The journal Aging aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)
Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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Journal
Aging-US
Method of Research
News article
Subject of Research
Animals
Article Title
Impaired renal transporter gene expression and uremic toxin excretion as aging hallmarks in cats with naturally occurring chronic kidney disease
Article Publication Date
20-Dec-2024
COI Statement
QL, BS, and JS are current employees of Nestlé Purina PetCare Company. JH, SK, MM, and EM are current employees of Nestlé Research. Vincenzo Sorrentino was an employee of Nestlé Research, which is part of the Société des Produits Nestlé S.A.