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February 18, 2020 – Dr. Kelly Diehl talks feline chronic kidney disease with Dr. Jessica Quimby, Associate Professor at The Ohio State University. They discuss the causes of this common disease of older cats and Dr. Quimby talks about her Foundation-funded research on how kidneys age and become damaged.

00:17 Kelly Diehl: Welcome to Fresh Scoop, Episode 17: Chronic Kidney Disease In Cats. What do we know, and where are we going? I'm your host, Dr. Kelly Diehl, Morris Animal Foundation Senior Director of Science and Communication. And today we'll talk to Dr. Jessica Quimby, a Morris Animal Foundation funded researcher and expert on feline chronic kidney disease. Dr. Quimby is an associate professor in Small Animal Internal Medicine at the Ohio State University. And Fresh Scoop is the monthly podcast of Morris Animal Foundation, one of the largest non-profit foundations in the world, dedicated to funding studies to find solutions to serious health threats to animals.

00:55 KD: In each episode, we'll feature one of the researchers we fund or one of our staff members, discussing their work in advancing animal health. Whether you're a practicing veterinarian, technician, or student, or just an animal-loving science geek, Fresh Scoop is the podcast for you. And you can learn more about us at morrisanimalfoundation.org. So okay, on to today's show, and today, we welcome again, Dr. Jessica Quimby. Dr. Quimby is a board-certified in Small Animal Internal Medicine and completed a PhD studying feline chronic kidney disease. She was on faculty at Colorado State University until 2017, and is now an Associate Professor at, as I mentioned before, the Ohio State University.

01:44 KD: Current research areas of interest include renal pathophysiology, novel treatment strategies, and feline clinical pharmacology focusing on improving supportive care and quality of life in cats with chronic kidney disease. Dr. Quimby has received the international Renal Interest Society Award and the AVMF Win Feeling Foundation Research Award for her contributions to nephrology and feline medicine. And Jessica, thanks so much for coming on today. I'm really looking forward to speaking with you because as a former practitioner, this was some problem that I saw all the time.

02:23 Jessica Quimby: Yes.

02:24 KD: And so before we get started though, tell me a little bit about you, personally, and your journey to veterinary medicine.

02:34 JQ: Yes, absolutely, and thank you so much for inviting me to take part in the podcast. It's a pleasure to do so as Morris supported several areas of my research. Well, I think it's been a fairly a long and cat-centered journey for me, honestly. I think at some point in time, people often ask how did I come about studying feline chronic kidney disease. And I think, similar to yourself, I had always wanted to be a feline practitioner. But when I was in practice, I saw this as just a major concern for cats, because the disease is so common and it certainly seems to increase with prevalence. It increases prevalence with age.

03:20 JQ: And so it was just really something that seemed to affect quality of life, affects the outcome for cats. And really, there were a lot of questions that we just didn't know the answers to. And one of the reasons why I came out of feline practice to come back to the university and specialize in internal medicine was really to try to answer some of these questions for cats, and to try to answer some of the things that we didn't know about chronic kidney disease and see if we could provide better therapies or at least improve the therapies that we have for those cats.

03:58 KD: And that's really interesting. And I wondered if you alluded to this in what you were just talking about, about the number of cats that are affected by this disease. And I've seen a variety of statistics, but what do you think are really solid statistics on how many cats get this disease? I've seen it at different ages. What are you seeing?

04:21 JQ: Yeah, it's a great question. And I definitely think that some of them were... Recent studies have given us a little bit better idea. We see numbers anywhere from, like you said, 15% to 30%, 50%, 80%. But it depends entirely upon the age of the cat. And there definitely seems to be evidence that the older they are, once we're in the mid-teens, we have cats living even longer now. As you're approaching 20, you probably have some degree of chronic kidney disease. And so honestly, from my perspective, especially at the university, we're surprised when we see an elderly cat in that age category that doesn't have chronic kidney disease. We say, "Where is it?", "Oh, there it is", or if the cat actually has healthy kidneys, everybody gets really excited. And so, "Look at you."

[chuckle]

05:15 JQ: That's amazing. So, it... At 10, I think that, at 10 years of age, it's a question, "Do we have kidney disease?" But definitely, as aging occurs, and we're being so much more proactive with feline healthcare now, and they're living longer, we are definitely seeing that maybe it's not their main problem but it does exist to some degree. And we have to be careful, we have to monitor those kidneys and make sure that we're protecting them as much as possible. And when it does become a clinical concern for that cat that we're identifying complications of disease and treating them.

05:50 KD: So, what are the thoughts behind the development of this disease? Because I think all of us who have practiced... Yeah, it's... You're right, it's a given in a lot of older cats but we don't see it that often in dogs as they age, and we certainly see some pretty elderly dogs, and they have their own problems. But why cats, do you think?

06:15 JQ: Well, it's... I think there's... Cats are no small dogs, we always say. And cat kidney disease certainly is a bit different than dog kidney disease. Dogs tend to more commonly have glomerular disease to start with, and cats tend to have tubulointerstitial disease, which seems again, to be related to their age for the most part. We often get... See cats unfortunately now that are forming stones in the kidney at a younger age, and they do seem to therefore, then be getting kidney disease or vice versa. It's kind of a chicken and egg question. But in general, we don't know the answer.

06:51 JQ: And this is certainly something that we've tried to look at with some of my research, but right now, I think the answer is, of course, to quote a common veterinary phrase, it's multifactorial and poorly understood, but the pieces that we do know that contributed to it certainly are age. The kidney itself ages normally. And we've been recently doing a little bit of research to look at that. But then, likely, throughout that cat's life, there's a number of small injuries of various ideologies that occur to the kidney, and those injuries probably build over time to an accumulation of actual clinical chronic kidney disease.

07:33 JQ: So, that's our current theory is that it's not just one thing, but you definitely have contributing factors. And then you have the age component as well. Our cats are living long enough now that the kidney is a little bit like the rate limiting step. If nothing else has happened to them, then the kidney potentially is going to become compromised over time.

07:56 KD: Okay, I have a question for you, and I don't know that I know this answer, other than I don't see grants in this area, which is, do we know anything about cats? Big cats, so lions, tigers are cats in the wild. Are they different or do they get CKD?

08:13 JQ: So actually, large cats do get chronic kidney disease, and especially with tigers and lions in zoos who live for a very long time, Dr. Rachel Cianciolo and I, and Dr. Shannon McLeland, my fellow researchers, we have... There has been some interest in looking at those large cat kidneys, and it's been reported before that there is a certain amount of chronic kidney disease in those big cats. And so again, that kind of is an interesting piece of information because it implies that it's not necessarily something that we're doing that would predispose our pet cats, right? It may be something inherent in the actual felid kidney along with that age component.

08:54 JQ: We can't really speak to what happens to large cats in the wild, because probably they're not living as long as those cats in captivity do. But I've certainly been approached by caretakers previously who have cats with chronic kidney disease, the big cats, to say... Actually, the question has come up, "What do we do for the appetite of the tiger with chronic kidney disease?" And we've absolutely prescribed mirtazapine for them, and said, "Here try this." So people are looking to also provide supportive care for those large cats, as they're faced with chronic kidney disease as well.

09:32 KD: Right. That was... And you... The point that I was making and you answered was right, is it something inherent in cats and their physiology versus this is something we've imposed on them or, right, if because they're just living longer. And so that's a really, really interesting thing because it would seem like it points to something about cats. Do you have any insights with your research? because I know this is a research interest, in how this problem, it is initially you said many small things, but do we have any sense of how that relentless progression starts, anything specific?

10:15 JQ: Sure. Well, the couple of different factors that we have looked at, we've done some work looking at senescence of the cells within the kidney, so as cells age, they sometimes stop replicating and become what we call senescent. And we've definitely shown that that occurs more in the elderly kidney, and much, much more in the diseased, chronic kidney disease kidney. And so that's something that is occurring as well as just last year at ACM, we had an abstract that we're now writing up, looking at what aging looks like in the kidney that is not affected by kidney disease. And that study was quite interesting because we showed that there are actually changes in the histopathology.

11:06 JQ: There's little bits of scarring and inflammation that are occurring in "normal cat kidneys," and those changes do increase with age. So there's micro damage that's occurring to that kidney even before they actually get to chronic kidney disease. And then if you add another insult on top of that, then that's where we might actually get them pushed over the edge into clinical disease. So that's something that has been seen in people. Those two different factors about how kidneys age. So that's part of our current area of research right now, is studying what the aging kidney looks like, so we can better understand what might predispose it to disease.

11:48 KD: And that was actually the... That's a good lead in to my next question, which was some of the research that you're doing right now and research even in the past, including some of your Morris grants, looking at different... Even if they didn't work out, can you talk about the different avenues you've pursued to look at this?

12:00 JQ: Yeah, sure. There isn't many. We definitely... I still... People say, "How can we cure kidney disease? "Well, they're all the very same, we’ll be very famous if we figure that out, but so far there has not been one thing that we've said, "This can really make a difference," but we've looked at a lot of different supportive care strategies, first of all, so like anti-nausea medications, probably most famously now the appetite stimulant mirtazapine has been very successful and that was some of our work looking at just... We really struggle with phosphate binders. What medications can we provide these cats?

12:53 JQ: We've looked at more novel type therapies as well, so we had also supported by Morris looking at some stem cell therapy. I had a long standing program when I was at Colorado State looking at stem cell therapy, and although we did see small amounts of improvement there in some kidney parameters, it was really hard to say that that was going to be a novel and strikingly successful therapy as in the way that we had administered it using the cell type that we use.

13:27 JQ: So still more work to be done there in the future, but in the time frame that I was studying that and with the cells we were using we weren't able really to see that that was going to cure kidney disease like it seemed to be doing in rodent models in the literature. We weren't really able to see that.

13:45 JQ: So, now we're looking more, eying up more of these pathways of senescence, we looked at telomere shortening as well. There are some therapeutic targets there that are very interesting as well, if we're really looking for a novel therapy. So that's kind of one side of it and of course basic science always takes a long time to come about but in the meantime, we looked more at that supportive care side, and looking for medications that we think will really help those chronic kidney disease cats out as they struggle through the course of their disease.

14:21 KD: And we had talked about this via email before about a little bit talking about medication. So let's start with mirtazapine and the... I can remember a little mantra I had in practice that maybe this was incorrect but we were starting... You get the cats that come in and they're not eating and they're not eating their kidney diet especially, right, and sometimes you just do... There are times I would tell people, "Well, it's more important to eat something," right? And then you're scrambling. So what about appetite and eating and the thoughts on fasting is probably not good when they're not taking in calories, and what are your thoughts about that?

15:07 JQ: Well, it's, of course, it's a subject that's near and dear to my heart [chuckle] in terms of how we manage our chronic kidney disease kitties, but one of the big points that I would make would be that I feel that we should be interceding much earlier in that process. We've done a number of studies looking at kind of what happens with uremic toxins and histopathology in the different stages of chronic kidney disease and most commonly people really see cats in stage three and four, either stage three and four struggling with appetite and their weight and losing muscle mass. But I'm also seeing cats who in stage two who are just not feeling well and they do have uremic toxins that are building up in their blood and they are losing weight and they are potentially already losing muscle mass.

16:01 JQ: So the very first step is identifying that process is already happening earlier in the stages of disease and being more proactive about assessing and monitoring those factors. Every single one of those cats should... The owner should know what it's caloric requirement is, and making sure that we're meeting caloric requirement and making sure that we are trying to save muscle condition, and save body mass before they actually lose it because once they get to the point of that really skinny muscle wasted cat who's eating hardly anything, gosh, sure, my appetite stimulant might help me out, but then I'm thinking I need a feeding tube here for this patient.

16:42 JQ: So we really try to strike in terms of appetite and caloric intake earlier in the game and try to get them eating much better at that time point. And then again, can I then get them to eat the kidney diet that I want? Now, we have all these choices for kidney diets and I've got different protein levels and phosphorous levels and potassium levels, and I potentially could pick one that the cat finds tasty that's formulated the way I want and really, really hone in on a nutrition plan for that patient. So I'm using the medications earlier, and I'm using them in a very targeted way to get the outcome that I would like nutritionally.

17:23 KD: What medication do you find that you add first? I think that's a big question in practice, right? Okay, so you know diet, okay, fine, but it sounds like obviously maybe an appetite stimulant, but is that your first medication typically?

17:40 JQ: Well, it's a great question because historically it's been famotidine, right, so there was a survey some years ago that said that the most common prescribed medication was famotidine, but actually there's been a lot of question recently about whether pathophysiologically that's the right thing to do. It's been a question that we've had for a long time. And so between my work and Dr. Katie Tolbert's work... And we actually currently have a grant together, that's being supported by Morris that is looking at these questions.

18:12 JQ: We just don't think... There's no evidence that cats with kidney disease actually are hyper-acidic. And so, the question of giving famotidine, which has actually been shown to A, not be as effective as omeprazole, and B, they develop tolerance to it quite quickly. So, the idea of chronically giving famotidine, it's a struggle to pill caps. And if I can't tell you that that pill is doing anything, then maybe we shouldn't be doing that. So, Dr. Tolbert and I have a study looking at omeprazole that's going right now, to try to figure out is it not hyperacidity, is there some other clinical benefit to giving omeprazole? Because people swear up and down they give this medication and it makes a difference, but we can't find a pathophysiologic justification for it.

19:08 JQ: My work looked at gastric gastritis, and gastric ulceration, and we found none of that in chronic kidney disease cats, not compared to how it is in humans and dogs, and her work demonstrated that they just weren't hyperacidic. So, if I have to choose a pill, it's not going to be famotidine, especially when faced with the choice of how to get it in to the patient. So, at least with mirtazapine, it does have some anti-nausea benefits to it, as well. And then now, of course, there's also the transdermal form, so you don't even have to pill the cat. And so, we may combine that potentially with other therapies for them, but I do reach for that sooner, definitely, than other things.

19:54 JQ: We sometimes will use maropitant chronically, in these patients as well. We did a study looking at that, especially if there's a vomiting aspect to their uremia. But I'd also say making sure that I control other factors, like underlying GI disease, is really critical as well. If they're having other GI signs because of concurrent disease, we want to get that under control as well.

20:16 KD: And so, that's good... Brings us to... Oh, the thing I really disliked thinking about when I was in practice, which was a phosphate binder. And because those are... I think we all struggle with those, and they’ve got to be timed. Is there really any good research to do that? It sounds like it would be down your list of medications. But where do you do it?

20:42 JQ: Well, so, here's the problem. And literally, every time someone asks me, "What do I need for kidney disease," I say, "Please, please give me a tasty phosphate binder that's a minuscule amount." [chuckle] So, because actually, when we start talking about nutrition and what happens with chronic kidney disease, this concept of metabolic bone disease, or mineral-bone disorder, which is a newer name for renal secondary hyperparathyroidism, incorporating that concept, we are actually really concerned about phosphorus, and keeping phosphorus under control. The idea, though, would be that your diet will do that if they will eat it.

21:26 JQ: So, I tend to first concentrate my efforts on getting them to eat that phosphate restricted diet. I'm less fussy about which one in particular it is, as long as it's lower in phosphorus, and then I'm using my appetite stimulant to say, "Okay, let's get that diet in." Then do we need to add that phosphate binder if I still have not met my phosphorous targets. And then we start speaking in amounts of phosphate binder if we have not met that target at that point in time. So, it is hugely important to control phosphorus. It's just that, I agree with you, phosphate binders are just a... They're a sticky wicket. It's just, the cats hate them.

22:07 JQ: We don't have very many good options, and here we are already fighting with appetite, and then we're trying to mix something with the food that can be given at the same time as other things. And yes, it's a challenge for the owner. So, if I could accomplish that through my diet, initially, that would really be ideal, and then say do I need that phosphate binder. But I still do hope that someone would bring us a better product for cats, that, again, in terms of what we're mixing in the food, that it would be not something that they're going to notice that would affect their ability to eat well.

22:49 KD: Yeah. I think that's challenging. So, just quickly in the last few minutes that we have, there's lots of other stuff, there's calcitriol, and there's how we treat anemia. And so, what... It sounds like definitely an appetite stimulant and anti-nausea medication might be really good things to add in early in addition to diet, which, you're right, we have lots of different options, at least, to give cats now. What else do you find that you use a lot or that you are more skeptical of using?

23:26 JQ: Well, I think one of the things that is an important point to make, is how very important hydration is, and that's probably something that we... is so simplistic that maybe we overlook it. [chuckle] So, there's multiple, multiple ways that dehydration could affect these patients, and like for instance, we often see constipation as a sequelae of chronic kidney disease, and dehydration itself may have negative effects that we don't understand. So, there's the simple things, like making sure potassium is normalized and the blood pressure is under control and like you said, treating anemia. But one very simple thing that we can also do is to really be monitoring and being aware of that patient's hydration status, and then trying to correct that as well, because it definitely can have...

24:16 JQ: I worry about this sequelae that has, even down to the level of appropriate perfusion of the kidney, and providing... Making sure that that kidney is perfused and it's not getting hypoxic for a variety of reasons. So, I don't want to forget that one, but yes, those are the big things. And we do frequently find that, of course these cats, like I mentioned, has hypertension, hypokalemia, and we have to make sure that we assess and address those aspects of their disease as well.

24:51 KD: Right. And I think sometimes just rehydrating these guys, even with sub-q fluids, I think can make a big difference in how they feel. So, I'm glad you brought that up because I think it's worth the trouble teaching people to do it.

25:07 JQ: Yes, yes.

25:07 KD: I have yet, knock on wood, I don't think I had anyone who gave it a valiant effort, who didn't know how to do it and even I taught my parents how to do it and, and you know what I mean, there are a lot of people I think who can master it in cats. So just to wrap up, and I know we covered a lot of ground and there's a lot more we could talk about Jessica but, summarize again what your take-home message for general practitioners who are out there who deal with this all the time, what they should really focus on that could make a difference for their patients.

25:44 JQ: Right. So I think, in short, we really need to think about how we assess all these very subtle aspects of disease. So their appetite, their weight, their muscle mass, all these metabolic complications that occur and making sure that owners understand it's important to check the blood pressure regularly or look at the urine or look at those electrolytes. And then in terms of the management, I'm just unfortunately, what I'm doing right now is just picking up the pieces. Right? So the disease causes this, and the disease causes that, well, I can try to fix the appetite, I can try to fix the high blood pressure and making sure that I have balanced everything that I possibly can to make them feel as good as they can.

26:30 JQ: And so that's part of my kind of messaging to owners is look, I don't have a cure for this disease, but here, unfortunately, are the 15 ways that things can go wrong. We need to look for each one of these complications and address them as they come along in order to get the best outcome for that patient.

26:48 KD: And it sounds like also interceding when they're at stage two. And for everyone listening, you really should go to the IRIS website and I think it's really important. I think I, in practice we started using it and really trying to incorporate it in our records as a way also of telling our practitioners who refer to us, "You really should be doing this and really looking at it," and it's a great website and it's really easy to navigate. And I think, as you said, really getting at stage two, and thinking about it because I think you're right, I think a lot of those cats are doing okay, right? And it's easy to just, "Oh gosh. Do I want to start initiating changes?" But what I hear you say is that you really should be into... You need to be thinking about being pro-active at that point.

27:39 JQ: Yup, yup. Yeah, we're definitely... I don't think we give them enough credit for potentially how... Cats are really good at hiding how they feel and hiding when they feel sick. And based on what we see in terms of studies that have looked at weight loss and muscle mass, there's already... And there's already disease happening in those cats and they're just hiding it from us. So taking a little closer look at them and being proactive, I think would really be helpful.

28:05 KD: Great, so Jessica, thanks so much for joining us. I think this is just such a huge problem and I've faced it in all my years of practice and I know people appreciate you talking with us, and good luck on trying to sort this out. I think it is a huge problem. And we'll be looking forward to seeing more grants from you at Morris, I know, and more of your work on this topic in the future.

28:32 JQ: Thank you. Thank you for having me, I appreciate it, Kelly.

28:34 KD: Alright, take care Jessica.

28:36 JQ: Yeah, you too. Bye.

28:37 KD: Bye bye. That does it for this episode of Fresh Scoop and once again, thanks to Dr. Jessica Quimby for joining us. We'll be back with another episode next month that we hope you'll find just as informative, and the science of animal health as we know and Jessica talked about is ever changing, and veterinarians, you... We really need to stay on and know the cutting-edge research information for us to give our patients the very best possible care, and that's why we're here. You can find us on iTunesSpotifyGoogle Play Music, and Stitcher, and if you liked today's episode, we'd sure appreciate it if you could take a moment to rate us so it's not just my mom and my kids and a few people inside Morris because that will help others really find our podcast.

29:22 KD: And to learn more about Morris Animal Foundation’s work, again, go to morrisanimalfoundation.org, there you'll see just how we bridge science and resources to advance the health of animals and you can also follow us on FacebookTwitter, and Instagram. I'm Dr. Kelly Diehl, and we'll talk soon.