Hello, I’m Dr. Hocheol Shin, or “Dr. Shin.” I study feline kidney health and aging at Greycoat Research.

I earned my Ph.D. studying cancer and immunology, and I’m now building on that experience to explore how we can help cats stay healthier for longer.

In “Reading Papers with Dr. Shin,” we’ll explore research related to feline health together. We’ll look a little deeper into how things work, what the studies actually found, and what those findings might mean for our cats. I’ll explain any unfamiliar terms as we go.

Ready to open today’s paper with Lulu? 

< Three-Sentence Summary >

1. When researchers examined kidney tissue from cats with chronic kidney disease, tissue damage was generally more severe in cats at later disease stages.

2. But the different kinds of damage did not all follow the same pattern, so damage to the filtering structures, cell injury, inflammation, and scarring needed to be examined separately.

3. At Greycoat Research, our starting point for product design is to understand what happens in a cat’s kidneys and consider which nutritional ingredients may have a role.

< Introduction — What Does “Kidney Damage” Actually Mean? >

So far, we’ve looked at individual nutraceuticals such as resveratrol, quercetin, and CoQ10. With CoQ10, we’ve reached the end of our ingredient-by-ingredient Nutraceutical Deep Dive.

Different compounds, but some familiar themes kept coming up: regulating inflammation, limiting cell damage, and supporting energy production. As we followed those studies, another question began to emerge.

“So what is actually happening inside the kidneys of a cat with kidney disease?”

That is where we’ll begin this time. We’ve been looking at what different compounds might do. Now we’ll follow what goes wrong in a cat’s kidneys, and what researchers are trying to change.

We’ll start with kidney tissue seen under the microscope. Then we’ll look at what blood tests can tell us, how body weight changes, and what happened in studies that changed the diets cats were fed. From there, we’ll move on to energy use and aging in kidney cells, and the relationship between the gut and the kidneys.

Along the way, we’ll ask why researchers chose those questions and what each study added to the work that came before it. Studies in cats will stay at the center. Where useful, we’ll bring in human and mouse research too, looking at what is shared, what is different, and what those findings might help us understand about cats.

One question will run through this series:

“When we talk about protecting a cat’s kidneys, what are we actually trying to protect?”

For this first installment, let’s begin with something more familiar: the numbers on a blood test report.

You may have heard something like this at a veterinary appointment:

“Your cat’s creatinine has gone up.”

“We’re classifying this as stage 2 chronic kidney disease.”

Those statements tell us that something is wrong. But which part of the kidney is damaged, and what does that damage look like?

Before we go further, let’s pause and look at what a blood test is telling us.

Creatinine is a substance produced by the body and cleared mainly through the kidneys. If the kidneys become less able to filter it out, more can remain in the blood. That is why blood creatinine levels are used to help assess kidney function. The test gives us an indirect view of how well the kidneys are clearing substances from the blood.

But knowing how much creatinine remains in the blood is not the same as knowing where the kidney tissue is damaged. That number alone cannot show us whether the filtering structures have changed, whether cells further along are injured, or whether scar tissue has built up between them.

So today, we’ll move from the blood test report to the microscope.

What differences do we see when we examine the kidneys of cats at different disease stages?

< Background — The Kidneys Filter, Then Take Back What Is Needed >

We often describe the kidneys as filters. That is true. But their work does not end with filtering.

Two steps happen in sequence: substances are filtered out of the blood, and the substances the body still needs are taken back.

1. The Glomerulus: Where Filtration Begins

Inside the kidney are small structures made up of tiny blood vessels. Each of these is called a glomerulus; the plural is glomeruli.

As blood passes through, some water and small substances are filtered out of the vessels. These include waste that needs to leave the body, but also things the body needs, such as water and glucose. The glomerulus does not select only the unwanted substances.

What would happen if all that filtered fluid simply left as urine? The body would lose useful substances along with the waste. So another step is needed.

2. The Tubule: Where Useful Substances Are Recovered

Fluid filtered by a glomerulus enters a narrow tube called a tubule. The cells lining that tube take water and useful substances from the fluid and return them to the blood.

What eventually leaves as urine has passed through this process of recovery and adjustment. For the kidney to do its job, the glomeruli need to filter properly, and the tubules need to recover what the body still needs.

That is why damage to tubular cells matters too. A functioning filter is not enough if the next part of the process is not working properly.

3. The Interstitium: The Supporting Tissue Between the Tubules

The tubules do not float separately inside the kidney. Supporting tissue lies between them. This is called the interstitium.

Today’s paper also looks at inflammation and scarring in this tissue. As we read the results, keep those three areas in mind: the glomeruli that filter, the tubules that recover useful substances, and the tissue that supports them.

< Today’s Paper — What Did the Researchers Compare? >

The paper we’re reading was published by McLeland and colleagues in Veterinary Pathology in 2015. Their question was:

“How closely does the stage of kidney disease, assigned using blood tests and clinical information, match the damage seen in kidney tissue?”

Here, stage means a way of classifying the disease. Feline chronic kidney disease, or CKD, is divided into stages 1 through 4 using criteria from the International Renal Interest Society, known as IRIS. CKD is diagnosed first. The stage is then assessed using repeat test results and other information while the cat’s condition is stable. Staging helps organize our understanding of a patient’s condition and guide care.

The researchers reviewed medical records and kidney tissue collected after death between 2000 and 2013. The study included 46 cats with CKD and 21 comparison cats whose blood tests did not show increased levels of nitrogen-containing waste products. No cats were euthanized for the purposes of the study.

They placed two sets of information side by side: test results from the cats’ lives, and kidney tissue examined after death.

On one side, they used repeated creatinine measurements and clinical information to assign a disease stage. On the other, two veterinary pathologists examined the tissue under a microscope to assess where the damage was and what it looked like. They then compared the tissue findings across stages.

Let’s look closely at two of those findings.

< First Finding — More of the Kidney’s Filters Were Extensively Scarred >

Earlier, we described the glomerulus as a small group of blood vessels that filters the blood.

Its normal structure can be replaced by scar-like material. This is called glomerulosclerosis. The researchers counted how many of the glomeruli they examined had extensive scarring.

Let’s pause here. What do these percentages actually measure?

The researchers were not measuring the damaged area of the whole kidney. They were counting the proportion of examined glomeruli with extensive scarring. The graph gives the mean of that proportion for each disease-stage group. A value of 25.7% in the stage 4 group does not mean that kidney function had fallen by 25.7%. As we saw earlier, the glomeruli are only one part of the kidney’s working structure.

The main point is that the percentage of extensively scarred glomeruli was higher in the later-stage groups. Differences between stages assigned using blood tests were also reflected in the kidney’s structure.

Did the other parts of the kidney show the same pattern?

< Second Finding — Inflammation and Scarring Did Not Show the Same Differences >

Before we look at that result, let’s spend a moment on what “scarring” means here.

Tissue contains more than cells. It also contains materials such as collagen that help support its structure. An excessive buildup of these materials between cells is called fibrosis. When kidney tissue is assessed for scarring, that assessment can include fibrosis as well as changes such as tubules shrinking or being lost.

Inflammation is assessed differently, for example by looking at inflammatory cells gathered in the tissue. Tubular injury concerns changes in the cells lining the tubules. All of these can be found inside the same kidney, but they are not measurements of the same thing.

So what happened when the researchers compared cats at stage 2 with cats at stage 3?

Inflammation in the interstitium and damage to tubular cells were more severe in the stage 3 group. But the scarring scores showed no statistically significant difference between the groups.

That does not mean the amount of scarring was identical at stages 2 and 3. It means that the study detected a difference in some types of damage, but not in others.

This is the part I found interesting. We can summarize disease severity with a stage number, but the different changes inside the kidney do not all vary in the same way from one stage to another.

So after asking “What stage is it?”, we can ask another question:

“What kind of damage stands out in that kidney?”

Staging helps describe the patient’s condition. Examining the tissue shows which structures were damaged in that condition. They are different ways of looking at the same disease.

< A Point to Keep in Mind — These Were Different Cats, Not One Cat Followed Over Time >

There is one important distinction to make here.

The researchers did not repeatedly examine the same cat’s kidneys at stages 1, 2, and 3. They compared kidney tissue collected after death from different cats, grouped by disease stage.

So finding more inflammation in the stage 3 group does not tell us that every cat moving from stage 2 to stage 3 goes through the same sequence of changes. The study also cannot tell us whether inflammation came first or whether another form of damage preceded it.

Only three cats were in the stage 1 group. More data would be needed to capture the range of changes that can be present in early kidney disease.

Even so, this study let us look at disease stages and tissue damage together in actual cats. It made the phrase “kidney damage” a little more specific.

< Personal Thoughts — One Paper at a Time, Together >

What caught my attention in this paper was the damage to the tubules and the tissue around them.

When we think of the kidney as a filter, it is natural to focus on the glomeruli. But in this study, injury to the cells that recover useful substances, and inflammation in the surrounding tissue, also differed between disease stages. I think understanding what happens in these areas is an important part of studying kidney protection.

Suppose we were studying a new approach to care.

Are we trying to help damaged tubular cells keep doing their job? To change the inflammatory response in the tissue? Or to limit the buildup of scar tissue? Those aims would lead us to look at different outcomes. We need to be specific about what we hope to change before we can judge whether it changed.

We can return to the nutraceutical studies we’ve already read with these questions in mind. When a paper discusses inflammation or cellular energy, we can ask: “Where might this matter in a cat’s kidney?” I hope the glomeruli, tubules, and surrounding tissue we looked at today give us something concrete to picture when that question comes up.

We ask the same questions at Greycoat Research when we review nutritional ingredients and design our products. What might this ingredient do in a cat’s body, and what evidence gives us a reason to consider it for kidney health?

I think we should be able to explain why we chose each ingredient for cats. That means looking at the research on the ingredient, but also understanding the animal that will be taking it. This is one reason papers that examine actual feline kidney tissue, like today’s study, matter to us.

As we read through this series together, I’ll also share which findings we pay attention to and how they inform our thinking about nutritional care and product design.

I’ve selected papers for a longer series that we can work through together. We’ll begin with changes inside the kidney, as we did today, then look at what blood tests can tell us, what happened when cats were fed renal diets, and how kidney disease relates to aging.

I’ll walk through what the papers found and share the parts I found interesting. Please share the questions that come up as you read, or topics you’d like to hear more about. Let’s get to know our cats’ kidneys better, one paper at a time.

As we go, we can put more detail behind the question that runs through this series: “When we talk about protecting a cat’s kidneys, what are we actually trying to protect?”

Next time, we’ll focus on one of the changes we met today: fibrosis. We know that scar tissue can build up in the kidney. But why have researchers paid particular attention to it? We’ll follow that question into a study that examined fibrosis alongside clinical test results in cats.

The findings discussed in this article reflect associations, mechanisms, and early translational evidence rather than confirmed efficacy in cats with kidney disease. Please consult a veterinarian before starting any supplementation protocol.

< References >

1.  McLeland SM, Cianciolo RE, Duncan CG, Quimby JM. A Comparison of Biochemical and Histopathologic Staging in Cats With Chronic Kidney Disease. Veterinary Pathology. 2015;52(3):524–534. doi:10.1177/0300985814561095.

 < About the Author >

Hocheol Shin, Ph.D., Greycoat Research

B.S./M.S./Ph.D. in Biological Sciences, KAIST (Korea Advanced Institute of Science and Technology)

Research background in cancer immunology, tumor microenvironment, and translational oncology. Currently engaged in companion animal health and longevity research.

[Educational Disclaimer]

This article is for educational purposes only and is not a substitute for professional veterinary advice, diagnosis, or treatment. It is not intended to diagnose, treat, cure, or prevent any disease.

Please consult your veterinarian before making changes to your cat’s diet, supplements, or care routine.