Chronic Kidney Disease Research at Basepaws

Chronic Kidney Disease Research at Basepaws

In the spirit of National Pet Wellness month this October, Basepaws announced its commitment to raising awareness about chronic kidney disease (CKD)—a major feline health issue from which one in 30 cats suffer. With our concurrent launch of the inaugural Basepaws “Feline Kidney Disease Awareness” month, we would like to take this opportunity to share details about our game-changing feline oral microbiome and genetics health research for the early detection of CKD.

Challenges Associated with Early Detection of Feline Chronic Kidney Disease

Chronic kidney disease often goes undiagnosed in cats until the illness reaches a more advanced stage because: (1) the early stages of the disease rarely present with easily observable clinical signs, and (2) when cats do develop symptoms, they tend to be non-specific, such as nausea or fatigue, further complicating diagnosis since these symptoms can be associated with a range of other issues.

It is usually in the later years of a cat’s life that confirmatory signs of CKD appear, when diagnosis is associated with a poor prognosis and treatment options are unfortunately more limited due to the considerable damage already inflicted on the kidneys. Currently, CKD diagnosis relies on a blood test and urinalysis, which are not routine during regular wellness vet visits. These procedures are generally invasive for the cat and expensive for the owner. 

A cat’s dental health connects to their overall health, as it can be a useful indicator of the potential for secondary issues to emerge. An elevated risk for periodontal disease, for example, is often associated with a cat’s higher risk for developing CKD. This dental condition originates below the gumline, making it difficult to diagnose in the early stages with routine visual exams alone. As is the case with CKD, once clinical signs are observable, periodontal disease has already reached an advanced stage. 

Early detection of disease, dental or otherwise, can also be difficult because cats are naturally inclined to hide pain and their pain thresholds can increase as a disease progresses. The relationship between feline dental health and general health, along with the challenges that can impede an early and accurate diagnosis, highlight the need for early-stage detection tools that can give pet parents and veterinarians a wider range of prevention and treatment options.

The Role of Dental Health Screening 

As one way to meet this need, Basepaws created the first ever direct-to-consumer cat dental health test as a tool for assessing a cat’s risk of periodontal disease, tooth resorption, and halitosis. The test supports early detection of these three conditions by identifying the range of microbes (e.g., bacteria, viruses, fungi, archaea) that constitute your cat’s oral microbiome. 

Basepaws’ innovative test involves an easy, painless, and non-invasive process. A pet parent simply swabs the inside of their cat’s mouth along the gumline to collect a saliva sample in the convenience of their own home. They then send the sample to the Basepaws lab using the pre-paid return shipping label included in the test kit.

At Basepaws, we analyze cat oral swab samples using the shotgun metagenomic sequencing method—the most comprehensive known to date for screening the full range of microorganisms in a cat’s mouth. Periodontal disease, tooth resorption, and halitosis each have predictive patterns of microbes that we call “microbial profiles”. These profiles are characterized by the different types of microbes present, the numbers within each type, and how the numbers from one type compare to those of another within the oral microbiome. The composition of the microbial profile is associated with your cat’s risk level for each dental condition, which has implications for their level of risk for other systemic diseases. 

We clearly communicate the results of our analysis in a digital report that a pet parent can share with their cat’s veterinarian to address any emerging issues and discuss preventative care and individualized treatment. 

Building a Body of Feline Oral Microbiome Research

Recent studies show that the oral microbiome composition of human patients with CKD differ from healthy control group patients without CKD. Canine-focused studies also correlate oral health with CKD, with particular attention to how periodontal disease influences this relationship

Feline oral microbiome research, however, is almost non-existent save for a modest number of scientific studies with comparatively small sample sizes of fewer than 100 cats. We are counteracting this trend with innovative research on Basepaws’ development of an oral swab based microbiome test for the detection of feline dental disease. This research investigated data from the Basepaws feline oral microbiome reference database—the world’s largest—with over 50,000 samples collected to date. 

We also gathered extensive owner-reported health history data for nearly 40 percent of our database samples. Basepaws is so grateful for our pet parent community of citizen scientists who provide this valuable information, which we analyze to find predictive oral microbiome patterns associated with a variety of other dental and systemic diseases.

Basepaws CKD and Feline Oral Microbiome Research

A current Basepaws research project is focused on finding CKD-specific signals in the feline oral microbiome. Figure 1 displays results from a preliminary analysis of our citizen science data for the project. Using our scoring algorithm based on the log ratio between pairwise microbial species comparisons in each sample, we obtain two distinct score distributions for our healthy controls and our cohort of cats with CKD (Figure 1, part A). We built a bimodal Gaussian mixture model based on these score distributions to obtain a probability score for a sample belonging to each distribution (CKD or healthy). Using this model, we can predict whether a cat has CKD with 78 percent sensitivity (a.k.a., the true positive rate) and 80 percent specificity (a.k.a., the true negative rate). 

To demonstrate the strength of the Basepaws analysis, we can compare its sensitivity and specificity values to other clinical diagnostic tools that exist. For example, though this at-home COVID-19 antigen test has a 100 percent specificity (true negative rate) for both symptomatic and asymptomatic persons, it has a much lower sensitivity (true positive rate) of only 64.2% for specimens from symptomatic persons and 35.8% for specimens from asymptomatic persons. 

Our preliminary analysis also identified 69 distinct microbes whose presence and relative abundance pattern in the oral microbiome is a strong predictor of CKD (Figure 1, part B). While there is some overlap between microbes that are predictive of periodontal disease and microbes that are predictive of CKD, there are also striking differences. Our CKD-specific research is providing us with new opportunities to investigate these differences and contribute to a strong body of scientific knowledge that can be applied to real-world scenarios for more effective preventative care and treatment.

Preliminary Results from Basepaws’ Analysis of the Feline Oral Microbiome as a Predictor for Chronic Kidney Disease (CKD)

Figure 1: Preliminary Results from Basepaws’ Analysis of the Feline Oral Microbiome as a Predictor for Chronic Kidney Disease (CKD).

Developing CKD Screening Tools to Improve Feline Health Outcomes

Basepaws’ at-home cat health screening products, world-class feline oral microbiome database, and cutting-edge research programs are advancing feline health by promoting pet parents’ awareness about the importance of preventative dental health care—and we’re just getting started.

The challenges associated with CKD diagnosis and management make clear the urgent need to provide accessible and affordable testing options that screen for CKD in cats and can help early diagnosis of the disease. With the preliminary data we gathered on CKD-specific signals in the feline oral microbiome, Basepaws is well-positioned to offer additional CKD screening products that identify CKD risk levels earlier, enhance at-home feline health care with CKD-specific recommendations, and provide avenues for cat parents and veterinarians to effectively plan preventative care, streamline diagnostic procedures, and prepare an individualized treatment plan.

The wealth of citizen science data that has contributed to the Basepaws’ feline oral microbiome database is invaluable to our research. Since these types of data are based on reports by cat owners and not veterinarians, however, there are limitations to the conclusions that we can make in our own studies. For current and future studies, Basepaws is working with veterinary clinics and universities to recruit controlled cohorts of cats that have a veterinarian-confirmed CKD diagnosis, as well as cats with a veterinarian-confirmed clean bill of health. Our veterinary CKD research partners include Ellen Carozza, LVT from Nova Cat Clinic in Virginia, California-based Dr. Steve Manyak, DVM of Pine Animal Hospital, and Dr. Nicole Martell-Moran, DVM, MPH, ABVP of the Feline Medical Center in Texas.

veterinarian kitten

This collaborative process ensures that the samples we obtain for our CKD and control cohorts precisely match the inclusion and exclusion criteria needed for the study (e.g., a confirmed CKD diagnosis and exclusion of additional, potentially confounding, comorbidities). In addition to augmenting our overall research program, this comparative approach will allow us to further evaluate the validity of our past research findings by analyzing the CKD-specific microbial profiles from our citizen science-based studies against those of the clinically recruited cohort.

As indicated in studies on CKD in humans, it is likely that there exist genetic factors that may increase a cat’s risk for developing CKD. In the near future, Basepaws will also conduct genome-wide association studies (GWAS) to identify potential genetic markers associated with increased risk of developing CKD. The GWAS will involve scanning the genomes from different cats (from our database and from clinically recruited control cohorts) and looking for genetic markers that can be used to predict the risk of developing CKD.

Basepaws is breaking new feline health research ground through its analyses of both host genetics and the oral microbiome. The identification of CKD-specific genetic markers will further our understanding of how genes contribute to the disease, but our efforts to uncover relationships between genes and the microbiome will potentially yield new combinations of results with diverse implications. For example, we can think of the oral microbiome as an indication of a developing/active disease process, and in identifying signs of this process we can more immediately plan and implement effective treatment strategies to slow the progression of a disease (or reverse it, if possible). If a cat has genetic markers associated with CKD but an oral microbial profile that is not currently indicative of CKD, planning and implementation of treatment may look quite different and occur over a longer period of time. 

With this unique, multidimensional approach to investigating CKD with genetic health and feline oral microbiome data, Basepaws and its partners are producing a rigorous body of feline health research to support the development of affordable, non-invasive early detection tools that can improve the quality of cats’ lives and help them live longer and healthier. 

If you are a cat parent based in the U.S. who would like to contribute to this important effort, we welcome you to participate in Basepaws CKD research. Cats diagnosed before the age of five are of particular interest to us. If you qualify for this study, you may be eligible for a free Basepaws DNA + dental health test*.

*U.S. participants only. Basepaws does not cover international shipping costs.

If you are a veterinary professional who would like to help us with clinical recruitment, contact us directly at: science@basepaws.com

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