So today we're talking about early detection, of disease, and we're talking about that from the perspective of preventative care diagnostics. So this is a joint session between, myself and my lovely colleague Rebecca, who will be covering the second half of this session. As far as our learning objectives for today, we've got a huge amount to try and pack into the next hour, so we'll try and get through this, as, as sort of quickly but as, as, interestingly as possible.
So the first half of the session we'll be looking at, preventative care testing and the benefits and plus the barriers to preventative care testing in practise. And then Rebecca part of the session will focus more on SDMA and preventative care diagnostic protocols, and what mild increases in SDMA may indicate and how to act on these, from a clinical perspective. So to kick things off, let's start talking about preventative care.
What do we mean when we're talking about preventative care, how do we define that? And I think for many of us, when we hear preventative care, what we think about is those preventative care things that us as, veterinary professionals are carrying out. So things like preventative dental treatments, prescribing anti-parasitics, giving vaccinations to animals, those are the things that immediately come to mind.
We might also be thinking about those sort of preventative care blood tests, . So biochemistry, haematology that we're running as wellness testing or pre-anesthetic testing on animals. But I think we very rarely consider things like, an animal's diet.
Is the animal being fed an appropriate diet for its life stage, an appropriate diet, for its breed? Is the animal an adequate weight? Is it overweight?
Is it being fed too much? Is it underweight? Is it not being fed enough?
Things like, exercise and mobility, is the animal receiving adequate exercise? Richmond, does the animal receive enough engagement, from its owner? Does it have toys to play with?
Or is it an animal that's left alone, sort of 12 hours a day where the owner goes out to work? So I think you can agree when we're looking at all of these, things in the preventative care umbrella or under the preventative care umbrella, it's really a partnership between us as the veterinary team, or the veterinary professionals, and the pet owner to ensure that preventative care, is, is done to its full capacity and that the animals are receiving the best, preventative care. So in saying that, if we focus a little bit more on preventative care diagnostics, so although we know it's a partnership with the, with the client to have good preventative care in place, I think offering preventative care diagnostics and wellness testing.
It's often a really, really difficult thing to us for us to do as ve veterinarians, and I think, we have a lot of barriers in our mind, and some of those barriers are, oh, it's expensive for the client, and I think this is a really common one. We've often got clients that have come in for, say, a vaccination. They're paying for their annual vaccination, and on top of that we've recommended wormers, we've recommended flea treatments.
They're already going out with quite an expensive bill as a result of this consult, or they might be signed up to to say some one of these practise health schemes. And, and for us to then recommend wellness testing for what is essentially a healthy animal on top of that, we often feel quite awkward about doing that and feel like we don't want to add any expense to what is already quite. A lot of lot of preventative care and expenses for the client.
And that ties into the next point, which is that we might feel that there's no value in normal results. So we might go to the length of convincing the owner that perhaps they want to do some preventative care diagnostics, or at least offering these. The owner might take us up on that offer and, and run the preventative care diagnostics.
But then we have that question of, well, what if the results are normal? And I think again, as veterinary professionals, Very good at identifying the abnormal results and, and finding out, yes, this is the problem. We've got the solution here.
Look what was abnormal in these results. But we struggle a lot more with receiving normal results and how to justify this to the owner that, oh, I'm due to run these preventative care diagnostics, and actually, everything was normal. And that back to that, problem that we're feeling that it's an expense for the client that could potentially be avoided.
Other barriers we might have is that of course it's time consuming. Of course it's gonna take a little bit of extra time to get that blood from the animal to run those bloods and to go through the results with the owner. And if that we haven't allowed ourselves enough in which to do that, that might be a barrier.
And with everything else going on right now with coronavirus and the way that we're having to manage console. So it's just gonna add another dimension of time to the to the consult that perhaps we think er is more hassle than it's worth. And I'm sure there are lots of other barriers that you, experience in your practise that are specific to your practise situation, or to your client's situations that may be causing you, to avoid suggesting these preventative care diagnostics.
But what I like to do is to kind of . Contradict that with some of the benefits of offering these preventative care diagnostics. So I think a big one which overcomes those first two barriers is a client reassurance.
So by offering these diagnostics to your client, you're going that extra mile. You're not just relying on your history and your physical exam to give you an idea of, of whether this animal is healthy, you're offering an extra level, you're offering. These objective, blood samples to check that the animal is in complete health, and the owner will feel that that's an additional, standard of care that you're offering.
You're offering them the best possible care because you've gone that extra mile and, and offered these blood results. And I think with the fact that, we're always concerned about what do we do with a normal result, how do we justify this to the owner, you need to think about. That owner and what might be going through their head, they might be worried about their, their pet that, you know, despite the fact they've not mentioned to you any anything about the pet being unhealthy, they might feel that the animal's been slowing down recently.
And by getting a set of normal results, that's a really good reassurance for them that actually, yeah, their pet is fine. We've checked all of these organs, and everything seems to be functioning well at the moment. There's also a really good clinical value in doing preventative care diagnostics.
So firstly, we all know that animals, hide disease really, really well, it's part of their survival instinct. And so there of course will be occasions where you will detect subclinical disease in an animal that's not showing any other signs. The other advantages, from the clinical.
Is that if you receive a normal set of results for an animal, this allows you to establish a baseline for that animal. So what might be a normal result for that animal in a period of health. And that's really, really useful when you're interpreting lab results going forward for that, animal.
And we'll explain all of this in more detail as we go through the presentation. So let's talk a little bit about the value of normal. So let's specifically start with looking at the value of the normal for the client.
So normal results are great, it's something to be celebrated with the client. But if you go do the blood results and then come into back into the consult. And just tell the owner, oh, everything was normal.
That really doesn't add a great deal of value for that client. That client doesn't understand what you've tested, even if you show them the results, they don't know what ALT is, they don't know what creatinine is. They have no understanding of what you've tested actually.
A normal result. So I've got a really nice quote here from Louise Dunn, who's a practise consultant, in the US, and she said, offer clients more value, give them a copy of the laboratory results, they'll put them on their fridge. And I that because I think it's absolutely true in that we see patients, many, many patients.
Patients every day, we're running bloods routinely, most days, and to us it's another patient, but to that client, that's their pet, that's their fur baby, that's the beloved member of their family, and it's really important to them that they understand these results and that they know everything, is going well with their pet. So what I'd suggest is that you can use some tools to help to communicate normal results to a client. For those of you that that use VetConnect Plus, you may be familiar with some of those tools.
For those of you that don't, VetConnect Plus is a platform for reporting, results, that's open, free of charge to all IDEX customers, and, we have many tools. On there we have a trending tool which will allow you to to share results more easily with, with clients. We also have an email function so results can be emailed to clients, but we also have this really nice client friendly summary function.
So this report here you see on the right for Lucy, is a client friendly summary. And that's if you get a set of normal bio. Chemistry or haematology results for a patient, you can generate one of these client friendly summaries, and it just goes through what was tested, in the patient.
There's even a, a freehand box at the top, that grade box, where you can fill in, some freehand details about the, the patient, perhaps something like, oh, the teeth have a bit of tartar, considered toothbrushing or a dental, . And it's something you can give to the client that they can take home. And I think clients get very, very sort of flustered, in consults.
There's a lot going through their minds. They have a lot of things that perhaps they've wanted to ask you, and they've been saving up for the past year, waiting for the vaccination appointment to go through these. And a lot of things get lost in translation.
They don't take in everything you're saying at that time. So it's really nice to have some. Something you can give the, give to them to take away, and that they can also share with their, other family members at home who perhaps weren't at the consult, to explain what was done that, done that day and what was tested.
And its real value to them, for running those preventatives. It actually means something, then they've got something to show, for that extra time, and financial investment that they've given. So that's the value of the normal for the client, but there's also a real value of the normal from a clinical perspective, and that's from the establishing a baseline, sort of, Theory, so we'll go a little bit more into this, it'll all become clear, .
So this makes more sense when we're talking about reference intervals. So there are two types of reference intervals. So there's what we call a population-based reference interval, which is exactly as it says, it's a, it's a reference interval that applies to a population of animals.
So these would be the reference intervals that you receive from whatever laboratory you're using or for your in-house analyzers, and they're things like a cat reference interval or a dog reference interval. We also have individual based reference intervals, and again this is pretty self-explanatory. This is a reference interval that's more specific to the individual patient, so looking at what is normal for that specific individual.
So if we look at population based reference intervals, all of these would be the same population based reference interval. If we look at the way population-based reference intervals are calculated, you take a normal distribution, and all the animals underneath this curve are considered to be clinically normal, animals. And to calculate the population-based reference interval, we take the inner 95% of that, curve, and that makes up the, the reference interval, the population-based reference interval.
And you can see by doing that, already we've got 2.5% of the clinically normal population that will fall below that reference. Interval or above that reference interval just in normal circumstances, that's just where they fall normally.
So the problem with population-based reference intervals is that because we're looking at a, a cat compared to a lot of other cats, we might have a cat that falls here with one of its blood results, we might have a cat that falls here with one of its blood results, or we might have a cat that falls here with one of its blood results, but all of those cats are considered normal, despite the fact that there's great variation between those individuals. And this becomes even more apparent when we're looking at the situation with specific analytes. So if we consider these two theoretical analytes, imagine that these box and whisker plots represent dogs.
So we're looking at results for 5 different dogs. On these box and whisker plots. And the grey area, if you're used to seeing sort of IDEX results in that connect plus, the grey area represents the population-based reference interval or the laboratory reference interval for these specific analytes.
You can see light on. There is a great deal of variation in this analyte between individuals, but there is not a great deal of variation within individuals. So we would say that this analyte has a high what we call index of individuality.
Now when we compare this analyte to the analyte on the right, we can see that there isn't a great deal of variation, between individuals for this analyte. So you could almost draw a straight line, across the middle of those box and whisk a plot. So it's not that variable between individuals.
It's more variable within an individual. So this, the analyte on the left, it would be far more. Advantageous to use a subject-based reference interval to interpret this analyte because it's so variable between individuals.
Whereas the analyte on the right, you would be fine to use a population-based reference interval for this one, because it's not so variable between individuals. I don't have enough time to go through all the papers and the evidence for this. As far as clinical research, as, as we're very limited on time, but there is plenty of published material on this.
If you are interested in reading more about which analytes, it's, it's more important to use subject-based reference intervals for, please go away and look at, articles and biological variation or index of individuality, and there is a lot of, open access stuff out there that you can read. So in summary, there's a key takeaway here from one of those papers, by Raquel Walton, 2012, is that for the majority of biochemical analytes and even for many hemostatic variables, population-based reference intervals are less sensitive than subject-based reference intervals for detecting pathological changes in an individual. So basically what we're saying is to get a subject based or an individual reference interval, it's going to pick up disease probably earlier than using a population-based reference interval because we know that some analytes are very variable between individuals, so you need to find out what's normal for your patients.
So kind of a, a more real life example for you to, to help you understand how this might affect the way that you practise or the way that you use preventative care results. I, I've got just a really, really simple example. So again, if we say the grey box here represents the population-based reference interval for this parameter, and let's say this parameter that we're testing creatinine.
So we're going to imagine this is a patient that's come to us, for a, we saw them for a general vaccination, we realised they had some dental disease, we booked them in for a dental, but they're 9 years old, and we just want to check, do some pre-anesthetic bloods because it's an older animal. We just want to check that everything's OK before we go, through the anaesthetic and the dental treatment. So let's imagine this data point that we have is creatinine.
We can see that it's in the normal population based reference interval for creatinine, but it's at the high end of the reference interval. How do we interpret this? Well, I think you can appreciate it's, it's quite difficult to interpret this without having any previous data, for this clinically, healthy patient.
So all we have is the single data point and we know that it's, within the population based reference interval. But what if we had some prior data for this patient? What if we'd had some baseline data from wellness testing in the past for this animal?
That data point now takes on a whole different meaning. We can see that this is an upward trend in that animal's creatinine, and that might prompt us to act a little bit sooner, that might prompt us to look a little bit further to see if there's any other supporting signs of renal disease. Before we anaesthetize this patient, we can now put things, into perspective, which we couldn't do before without having those prior data points.
And this, by the way, is taken from, again, VetC Connect Plus, which allows you to trend your data, it's a really, really useful thing for clinical interpretation, but also a really useful tool to help you communicate to clients, about what's going on with their patients. So I hope that's kind of highlighted to you that normal can be really, really useful in, in the context of preventative care diagnostics. But now I'd like to go a little bit into more the, the abnormal.
So what is the likelihood of us detecting something abnormal, with preventative care diagnostics? How many patients typically have subclinical disease? So I've got a few, papers that I just want to quickly go through with you.
So we're going to focus on these two main papers. So the first one is Willems at A, which was published in 2017 in the Journal of Veterinary Internal Medicine. And that looked at canine, so it's 100, apparently healthy dogs, and these were, just.
Senior and geriatric dogs, and the key takeaways from this study was that physical and laboratory abnormalities were common, in healthy elderly dogs. The second paper we're going to look a little bit further into is Delosa and Yanks, and that was published in 2016. In the Australian Veterinary Journal, and this looked at middle aged, cats and dogs, so cats 6 to 9 years, dogs, 5 to 9 years, and that again concluded that that abnormalities were common, and that, by doing preventative care checks in animals, you, you can often detect subclinical diseases early and allow earlier intervention and better health outcomes.
So looking a little bit further into the Delosa preventative diagnostic study, as I've said, it was cats and dogs in this study, middle aged, and all the animals had a haematology or a CBC, biochemistry, including pancreatic lipase, and a urinalysis. And the majority of both cats and dogs had abnormal results. So for the canines, only 55 had blood work that was all within the normal reference intervals.
And for the felines only 26, had blood work that was all within the normal reference intervals. So the majority of patients. Numbers that were outside the normal reference intervals, not to say that they were indicative of significant disease, but this again I think highlights why it's important to have your subject-based or individual based reference intervals rather than going on the population, population based reference intervals.
When we're looking at significant disease though, or significant laboratory abnormalities, there were also a, a large number of, of animals that had, quite significant subclinical disease. So 6.2% of the canine patients had laboratory abnormalities that were diagnostic of significant disease or needed additional evaluation or additional follow-up.
And 19.1%, which is pretty huge, I think, . Of the cats had laboratory abnormalities that were diagnostic, or significant disease, or needed further follow-up.
And some of the diseases that were detected as a result of this study or the conditions that were detected with things like anaemia, inflammation, hepatic disease, renal disease, and pancreatic, disease with some of the, findings of the disease states that were diagnosed as a result of this, study. Remember again, these are healthy, middle-aged cats and dogs. And then just to touch on the the other study, Willems at this study was looking just at at canine patients again these patients had a haematology, a a CBC and a urinalysis.
And I think we've already, highlighted that the conclusion was that abnormalities were common, which I think we're all probably fairly clued in that as animals age, these abnormalities were more like more likely to pick up these abnormalities. But a kind of a take home, I feel that that should be taken out of this study is really from the urinalysis point of view and in the There were quite a few urinary abnormalities detected in this study, so, we had, a lot of crystals in the urine. So 62 of the 96 dogs, that's 65% of the animals had, crystal urea detected.
30% had casts, 30% had microscopic hematuria. And 5% of these, had bacteria found with 4 of them having a positive urinary culture. So it's kind of for me a take home.
I think urinalysis, I know Sarah has touched on this as well, earlier today, but urinalysis is something that I think sometimes, we, we don't always do as frequently as we should. It's something that gets, left on the sideline a lot, but it can be really, really useful. It can give us a lot of information, that our blood results, can't.
So it's really, really worth including urinalysis in your. Preventative care checks. I think for this study in particular, one thing that really resonated with me is in the conclusions, the, the, authors of this study had said that, actually when they probed some of these owners a little bit further, the owners that had, animals that had, urinary infections, they had, they did mention that, yes, so actually she had been weighing more.
But the owners hadn't mentioned this initially because they just felt that, the urinary problems were not important, that it wasn't something, that, that they were really concerned. Worth doing your urinalysis because it might be something that your owners are not even reporting is a problem or they don't perceive it to be a a medical issue. So obviously at IDEX we have access to huge amounts of data with our reference labs and our smart service on our instruments.
So we decided to do a little bit of our own investigations, and use what we call big data, to get an idea of, of the number of preventative care profiles that are finding abnormalities. So what we did, a couple of years back now was looked at, over a quarter of a million wellness consultations, from over 5000 clinics in North America. And we looked at a these animals had had a CEM 17 plus electrolytes, SDMA and a haematology blood sample run.
And we divided these animals into categories based on their age, so we had the adults, the seniors, and the geriatrics. And what we wanted to do from that point is define, well, how many of these animals, had abnormalities that required, further follow-up. So we were defining this as animals that had, 3 or more biochemical parameters outside of the, reference interval mythological parameters, that were indicative of, of underlying disease.
And we found that, for the adults, 1 in 7 of these healthy, animals, that, that were having wellness bloods, had, findings that demanded further follow-up. 1 in 5 seniors and as many as 2 in 5 geriatric patients, had results that demanded, further follow-up. So I think that, .
Also ties in with those previous studies that I've mentioned that subclinical disease is probably more common than we realise and if we're not testing, then we're not picking up these subclinical diseases and, and being able to institute early intervention with these patients. So if we want to start doing preventative care diagnostics, what should we think about including in our preventative care panels, what would be useful to include? So I think haematology is, is obviously a great starting point.
Haematology is probably one of the most sensitive, panels that we have. It will, it will detect disease often before biochemistry does. So, including a haematology or a CBC, allows you to get a really good idea of the general health of that patient.
Is there something we should be looking into, further? And it's also really good at giving. Idea of the health of that of the patient at this time point, because haematology changes so quickly, it allows us to identify what is going on with this patient right now at this moment in time.
Biochemistry obviously is going to give us a nice oversight into what's going on, with the organ system function. And then obviously urinalysis completes the picture, so we can't interpret things like, azotemia if we don't have urinalysis. And also to my point earlier, there are, urinalysis is often something that just doesn't get done as often as it should, and there may be things that get missed, in the biochemistry and the haematology, if we're not doing the urinalysis as well.
So we'd recommend to include, all three of these in your preventative care testing if you want to start a, a, protocol. If you're not doing anything at the moment, I think a good starting point would to do would be to, start to introduce a geriatric clinic or a geriatric testing could be something that, your nurses play a big role in, in running, or, pre-anesthetic testing if you're not doing it. And, and pre-anesthetic really the starting point as well because it starts to introduce your clients to that .
Of life stage testing. So with pre-anesthetic, you could divide it into certain tiers, adding, more tests as an animal gets older. And that just gets owners thinking more about that life stage testing as well.
And that can really, really help when you want to go that extra mile and start a, a wellness testing protocol, if people are used to knowing that they're, they're gonna get more tests added as, as that animal ages. So what about SDMA? I mean, I've been talking for quite some time now, on an, from an IDEX speaker, and we haven't had much of a mention of SDMA up until this point.
So of course, SDMA is an essential element of your chemistry panel. For those of you who don't use SDMA or are not that familiar with it, I know it's been mentioned in some of the other talks today, but just as a reminder for you, so SMI SDMA is a methylated form of the amino acid arginine, and it's. Closely correlated with glomerular filtration, rates, so it's an inverse correlation.
So as the glomerular filtration rate declines, the SDMA will increase. And SDMA has a lot of advantages in that. It's a sensitive indicator, detecting, loss of kidney function with as little as 25% loss.
It can be more reliable than other parameters like creatinine because it's not impacted by lean, muscle mass like cre creatinine is. It's an early indicator of disease. It often, increases before other parameters do.
And it's also because it's closely related to GFR, anything that affects GFR will cause a change in SDMA. So that may be indicative of other concurrent disease. It may point you towards, something going on that's affecting, having a knock-on effect on the kidney on the kidneys and just encourage you to delve a little bit deeper.
So when we go back to looking at this data that's come from our sort of IDEX labs, we, what we did was sort of think about how, SDMA is impacting preventative care profiles and how does it impact preventative care profiles when we do include it and when we don't include it. So we separated the data, into profiles with SDMA and without SDMA and compared them. And what we found is that when you include SDMA in a preventative care panel, you really increase the chances of finding abnormalities that require further.
So if we're looking at those three, age groups that we defined earlier, we found, an increase 20% of adults, 40% of seniors, and 40% of geriatrics that required further action, on their preventative care profiles with the addition, of, SD. May compared to without the addition of SDMA. And I think in preventative care panels, a lot of the, elevations that we will be seeing in SDMA will be those milder, elevations.
So in the 15 to 19 mcg per deciliter range. So I'm gonna pass over to my lovely colleague, Rebecca now, who's going to, go through with you in a little bit more detail, as to how to interpret these mild increases in SDMA, and what they mean. Great.
Thank you, Sylvia. Can you confirm that you can see my screen? Yes, I can see it.
Yeah. OK, great. So I'm so happy to be here today.
And I do wanna speak, directly kind of about these mild increases in STMA, and the reason for that is, you know, as it ties into preventive care. Where, a lot of times we often see mild increases of STMA first, especially in our screening cases. So these are animals that commonly come in that might not have any clinical signs or we're seeing them for a separate issue and when you run your lab work, you find that they have a mild increase in STMA.
And when we speak about mild increases in STMA, you know, we're talking really about 19 mcg per deciliter. And, you know, this makes up typically about 60% of the results that were from the reference lab, and so it's definitely going to come up as you are, discussing preventive care, but also in your kind of sick patients or your pre-anesthetic patients. And so we felt like it was really important for us to try to answer the question.
About what is that mild increase represent in all these kind of different classifications and how often does STMA remain increased, right? What is that, that initial increase in STMA telling me? Where does creatinine fit?
So I think it's always important to utilise all of your biomarkers, especially when you're thinking about mild increases. Really helps to get a full kind of robust picture of, of kidney health and so that's really important. And then what do I do next, right?
What do I do for my patient? What do I suggest for my owner as a practitioner, you know, how do I increase and what steps should I take to, more fully investigate? And so, you know, how can we tie that into this idea of mild increases and how they can help you.
And this ties back to kind of what Sylvia was talking about in terms of preventive care and in terms of baseline. So knowing where you're Animal starts, can be really helpful. And sometimes mild increases don't always mean that you have a red, result, right?
It doesn't always mean that you're outside the interval. Sometimes a mild increase, is just that that is a significant change for that. An animal.
So when I think about mild increases as a practitioner, you know, with SDMA I do think about this kind of 15 to 19 mcg deciator range for specific gravity, you know, often, I'm thinking about, you know, a 1020 to 1035. So sometimes with cats, right, if you've had a cat that was 1060 and then all of a sudden they're 1045, you know, specific gravity, that could be a significant change for that cat. Same thing with creatinine, right?
You know, we have reference intervals for creatinine and They are population based and so a lot of times the individual creatinine value and the animal's baseline, right, to, you know, follow up lab work and trending lab work is actually really important in interpreting creatinine. And then I put UPC on here mainly because proponent of UPC and using that to help kind of gauge the level of kidney disease that you might be dealing with. And so when we look at these mild increases, right, within and outside of the reference interval, you have to think about the individual patient, right?
So CAT versus Dog, what type of disease do they have, right? Is it a primary kidney disease or do you have a kidney disease with another disease like diabetes or hyperthyroidism, right? What is the aetiology of that disease and how might it affect your biomarkers where your increases need to are a little objective, right?
And then reference intervals, which we touched on earlier. Reference intervals are, are a great resource to help you kind of think about, a single point in time, but a lot of times understanding that that patient's individual interval will give you a little bit more information. And then demographics, right, breed, muscle mass, even sometimes geographic location, those things can all be really important in assessing these mild increases.
When we think about SDMA specifically, we thought we would take the opportunity to use our access data to review what are the trends that we see with a mild increase in SDMA. And really what we were thinking about is, can we establish persistence, so meaning how often does SDMA remain increased. Is the behaviour of these increases in STMA alongside some of our historical biomarkers like creatinine.
And so, what we did is create a study designed to kind of investigate that using what we call big data. So that means basically that we took a tremendous number of laboratory results, and so in this case, we screened about 3.6 million dogs and 1.6 million cats from the reference lab.
And this data is based in North America. And we asked that they have some basic inclusion criteria. We wanted to have serial testing sequential, right?
So we needed them to have a certain number of tests, and we also wanted them to start within the reference intervals. So we asked that these animals have creatinines. And SDMAs that were initially within the reference interval.
And that was really our goal was to really look at animals with either first-time increases or very subtle disease, right? That you might be capturing on a preventive care profile or even a sick patient profile. And, and not to already had established kidney disease or also trying to avoid looking at animals with acute injury.
And we did that and we'll talk about this a little later by certain time restrictions. And by the time they entered all of inclusion criteria, we ended up with about 16,000 dogs and about 16,000 cats that we could evaluate a little bit more closely. And so, you know, when we talk about persistence, so the idea of looking at how often does a biomarker stay in.
Trans versus the upper reference limit, right? And so the diagram, I think is really helpful. You have a time 0, right, which is when the animal had a normal STA and creatinine.
And then we, a qualifier was that at a next time point, and there was no time restriction between time 0 and time 1, that the STMA was above the reference interval. And then our question was what happens at time two? Does it say increased or does it return to within the reference interval?
And we ask that time 1 and time to be at least 14 days apart, but no more than 12 months apart. And our goal there was to try to eliminate some of our acute kidney injuries. Undoubtedly, we'll capture some acute recovery still.
Right, with big data, unfortunately, you don't have the luxury of being able to exclude based on diagnosis and all of these things and so we'll talk about that a little later. But this allowed us to basically weed out a lot of those acuteities that we capture in this particular study. In the population where we established persistence.
So when we looked at these animals, they continued to have an increased STMA at time 1 and type 2. We were interested to know what happens with creatinine because by establishing persistence, we're much more confident that these animals had a continued impairment in GFR and we really wanted to know where does creatinine. Fall with those animals.
When does it increase? Is it at time 1, type 2, time 3? What are the patterns that we could see that might help us understand what a mild persistent increase in STMA is?
So all of this data, it ties around an animal that had initial increases in SDMA between 15 and 19. So time one was between 15 and 19. So that's really important and it does represent the majority of the population that we looked at anyway.
And so, just remember that as we kind of go through this data. And so this helps me so understand kind of how the population builds, right? So we had animals that qualified, animals that we could establish a persistently.
And then we looked at creatinine in those animals where we knew their STMA remained persistent. Excuse me. And so, what we found is that persistent increases in SDMA, meaning they had two consecutive increases.
48% of them remained persistent at time too, with 52% having GFR restored. Now, at first, when you see this, you know, you think, OK, 48% doesn't seem exceptional, but you have to think about it in context with the normal population. So that would be a population.
Or you've never had an increase in STMA before, what would the likelihood be that your next STMA would be increased, right? So that an animal that never showed evidence of impairment at GFR, and then you did lab work, what would the likelihood be that you would see it? And so what we found is that When we looked at those populations, there was a drastic difference between animals that had already had a single DMA, so meaning that their time one was increased and those that had never had an increased SDMA.
And so, this kind of boils down to the fact that the probability persistence, is Represents a five-fold increase in risk for continued impairment of GFR. So meaning that once you've had an increase in STMA, you're far more likely to continue to have an increase in that biomarker. And that's cause we know persistence or persistent increase in a biomarker is much more important than just a sole increase.
Though, as we look at it a little bit further, we'll see that those soul increases can be important as well. And so what you can see here is even between a 14 and a 15, this kind of 14, less than 14 represents the general population, there's a difference, right? And as you go up to 19, You continue to see.
That difference represented. And then as you would expect, if you have an initial increase in ST even higher, you then you see greater persistence. And so I think this is a really important concept.
We did do this study in creatinine as well and We found very similar patterns. And so this is really normal for a kidney biomarker looking at function in terms of a population. And so, I think it's really important to recognise that SDMA once you have that initial increase in SDMA, you should have a greater expectation of continued persistence.
No, we didn't want to leave out this 52%, right? We wanted to think about them a little bit why we could see that restoration of GFR. And so there are a couple of different reasons.
When we think about big data. We're not really able to go in at this point and show what treatments that each of these animals have, you know, what, what is the diagnosis that the veterinarian gave, right? And so when we hypothesise, we can know that some of these animals would definitely have had treatment, right?
Whether that's fluids or antibiotics or anti-hypertensives, those are all things that could cause restoration of GFR along with compensation, right? So compensation, we don't always think about it, but it's really common for us to see. Compensation occur, in the form of hyper, so basically the, kidneys kind of buff up a little bit.
And then also in terms of osmality, kind of a complex topic about sodium, and then modification of renal vasculature. So that has to do with like the efferent and afferent arterials and how those can modify themselves to help with blood flow. And then we have repair for minor injuries.
So I think we've all seen plenty of cases where animals come in with a minor, like, we do some lab work, we find a mild increase in our renal biomarkers and we don't really know why, right? Sometimes that could be dehydration. A lot of times I use the example here of if you go on vacation for the weekend and you've Your young healthy cat in the basement or in a single room without access to food and water, you know, they can conserve for a while, but they'll certainly be dehydrated.
And if you check their biomarkers at that point, you'd certainly see a change, certain injuries from medications, toxins. So, I think we often see repair for minor injury, especially in our younger population. And then early stable chronic kidney disease.
I think this is a really important category. You know, I think if we reach back to physiology. And recognise that GFR glomerular filtration rate is really, really variable.
That can be reflected in your surrogate markers like STMA and creatinine. Remember, you know, we have these reference limits, but those are just for a population, not an individual and so it's not uncommon for animals to fluctuate around the upper reference limit, both for STMA and. If they call this population wafflers.
I think that it really represents what they're doing, right? They have disease, they have impaired GFR, but sometimes they're compensating, sometimes they're not. Different days produce different GFRs, and that's reflected in our in our surrogate biomarkers, and so we see them waffle around the upper reference limit.
And so these are all really good reasons that you might see. A, animal that had an increase in SDMA, then also dropped back down, into the reference interval on your next test. But we were interested to find out what happens to this population over time, right?
Do we see additional evidence of impaired GFR? And so what we found is that yes, we do. So in this population where we had restoration, we followed them for an additional year beyond their T1 value.
And so what we found is that in about half of those patients, so a 25% of the total population, we actually saw STMA increase again. And so, meaning that it came back up above the reference limit. And so that really starts to, to speak to the idea, that a single or sole increase in STMA, can be an indication that you have an animal in a totally different risk category, which speaks back to that earlier conversation we had about the percentage that remained persistent.
And so for me, what this says is that alongside that persistent population that if you establish persistence, there is this other population that probably has some impaired GFR that our functional markers may not be consistently telling us about, but it's really important to recognise before you do things like anaesthesia or certain medication choices. Now, there's a whole, there is a section of the population that within this year time period did not go back up again. So whether that is animals that are getting consistent treatment or animals that had repair for minor injury, right, or are continuing to compensate, I think that this is pretty normal for what we would see and also very normal for what we see with creatinine in a similar population.
And so, you know, say as a statement is that within 12 months of a single mild increase in STMA, so 15 to 19 as your initial increase, 72% of patients in this study risk further impairment of kidney function. And this study is pretty representative of our population of expectation, right? Most of these animals are on the far side of, you know, 5 years old, so adult or older, and certainly, you know, so I think seeing what we see is pretty representative that some of them are gonna have persistent increase and then I think this really interesting population where we see an additional increase even if we're seeing SDMA move in and out of the reference interval.
So I think that that's really important to recognise. You know, I, I also think it's always important to think about creatinine. I think STMA is a great marker and It opens up a lot of windows for diagnosing certain types of early disease or, you know, really being contributing to early persistent diagnosis.
But I think always, you know, my recommendation is use every tool in your toolbox, right? And so I always recommend that STMA and creatinine be used together. That gives you the best picture of kidney health, right?
And sometimes markers. You know, work better for other patients. And so it's always important to recognise just as we're talking about like individual, reference intervals, dual animals, are gonna be reflected differently in analytes.
And so you may figure out that 11 analyte works better for you with a certain animal. And so I would just say, you know, as we think about why we look at creatinine, it's because creatinine remains important. But it's also important to kind of that we were able to This particular study.
And so what we found is that in animals with that initial mild increase in STMA who were persistent, often SDMA was the first biochemical indicator. So if you look at this graph, you have months since their T1 STMA. So that's months since their first increased STMA along the x-axis, and then patients with an increased creatinine.
So this is the percentage of patients at this time point that then had a of the reference interval. So basically, both biomarkers were abnormal. And so what we found is that 81% of patients with mild increases in STMA, That was the only biochemical marker at the time of, of entrance into the study.
And so that's really interesting and kind of helps reinforce the SDMA earlier in a portion of the population, right? And so how helpful it can be, if you're using it consistently, for screening and also, you know, in, in clinic cases where you have clinical suspicions. The second really interesting fact is that we didn't see in these mild persistent cases, only about 50% of cats and dogs then had an increased creatinine by 1 year.
And so what this tells me is that when we see an early mild persistent increase in STMA, you can think about GFR probably on average somewhere around 40% loss, right? And in the course of a year, when you see creatinine come up to join STMA, you think more along the lines of an animal that has GFR loss of about 65 to 75%, right? And so what this is telling you is if you can establish some persistence with SDMA early in the course of your investigation, that can tell you much, much sooner that you might have an animal that has the potential for progression, right?
And so that's incredibly important because we still struggle with understanding what animals will progress more quickly, where they fall into categories, right, both cats and dogs. And so knowing that you have a persistent increase in STMA can help give you kind of a concept of what your timeline is. And, and I think for me at least, that's really important when I'm having a conversation with a practitioner.
About what's the next step or and, and then from there, the practitioner to the client, you know, how do we deal with this? What is our rate of testing, when do we test, right? And so I think that those things are really important and this data kinda helps, you know, show, that while both biomarkers are important, it also reinforces that You know, especially in mild increases of STMA there is really good value in those findings, both the ones that are persistent and single, right?
And so it would encourage, you know, follow up, you know, within 2 to 4 weeks of an increased STMA and then even in animals where you see them, you know, go back into the reference interval or have restoration. Think about, OK, if I'm going to challenge this animal, whether it's anaesthesia or medication or the animal has some sort of other sickness, right? Remembering that this might be an animal that gave you a red flag about their kidney function.
And in really committed owners, I would simply recommend following up in 6 months with an additional, look at your kidney biomarkers to try to determine what might be that animal's particular pattern. And, and so I think we always have these conversations about STMA, you know, versus creatinine, and I think that that's the wrong decision to take. I think that both of them have incredibly important roles in kidney disease.
We know that there are some inherent, weaknesses, around biomarkers, and that has to do with the individual patient, right? And so I do feel that often STA is slightly better as a single time. Point indication of decline in GFR, and that these mild early increases are really important.
But I also feel like it's important to have creatinine and to try creatinine and to use them together. You know, I always recommend to people, think about how many animals you need to benefit before you run a pretty non-invasive test, right? And STMA is a pretty non-invasive test.
For me, you know, that, that doesn't have to be that. 1 in 50, right? That's still maybe a day and a half of work, right?
But in this case, STMA helps you with a lot more than that, especially in our, in particular populations. And so I think that's encouraging for using it both in your preventive care, as we kind of talked about earlier and how it can help you identify more cases that need follow-up, but also just in general, right, as a as a renal biomarker, just kind of part of your normal toolbox. I think that creatinine is still a really good tool.
You just have to size, pre comorbidities diet, right? These are all really important things for creatinine. I think the bottom line is that both preventive care and individual patient baselines are essential for really understanding and recognising early changes in kidney disease.
So, and a lot can be said for being able to know for dealing with that, especially if you, as you have animals entering their kind of senior and geriatric phases of life. I wanted just to wrap up with some key takeaways. So, I mean, I, you know, personally feel that preventive care is really appropriate for life stages.
You know, I have my own animals that have had preventive care and it actually has been helpful in several cases when thinking about medicating, I have a border collie who needed NSAIDs, right? And by trending him, I could tell, right, that he is renal Function wasn't as good as it should be. And so it was good for me to be able to recognise that for follow-up, that there's value in the normal.
And that's something we have to work really hard with educating our clients, but having a baseline, knowing that your animal is normal can be really helpful if you have some sort of acute event, but also in the course of that animal's lifetime, right? It can be really important. Remembering the minimum database.
So I think that, you know, having haematology and chemistry and urinalysis, those three things really give you a lot of information and are really important. And then really tying your whole staff in with that client education aspect and making it easier for the client to come along that journey with you. And then, you know, from the perspective of the renal franchise, and, you know, the renal perspective, I think that SDMA plays a really important role in that preventive care and that baseline understanding.
And so trying to think about incorporating it into your thought process when you think about looking at kidneys kind of holistically, right? Continuing to run the biomarkers that you know, are gonna give you certain types of information and recognising that there are other biomarkers out there that can Really broaden, give you a broader bandwidth for understanding kidney health, which is essential, right, for long-term survival both in our cats and, canine patients. And so, starting with preventive care all the way through, you know, all of the care that you provide over the lifetime of an animal, you know, these things are really important, I think, to increasing quality and quantity of life for both our feline and our canine population.
So, with that, we are done, and I just wanted to take the time to thank everybody for hanging on with us and, and being a part of this. I did notice that we had a couple of questions. Hi, yeah, we do.
Thanks for that. Are you happy to read through them or do you want me to, yeah, I'm happy to read through. So the first question is, during this SDMA persistence study, was urine specific gravity evaluated?
That's a great question. So the answer is yes, but we don't share that data for two reasons. One is, unfortunately, a lot of times urine is a reflex test.
So once you know Coming in full presentation, then you get a urinalysis. And unfortunately, what that means is that a lot of times that skews the sample to being abnormal. So it's a little bit hard for us to look at it comparatively.
But what we did find was that as values increased, so as STMA increased over time, USG followed that same positive correlation, well, I guess in a way a negative correlation, so got lower and lower as values got higher and higher, and a good portion of these animals at the time that persistence was established also had a decrease in urine specific gravity. So I, I think urine is incredibly important and I think a lot of times, and we won't get into this today, but based on the aetiology or the type of disease that you have, urine specific gravity can be an earlier indicator, or can be can can help you, a concurrent indicator or it can be later, right? And that really depends on tubular versus glomerular disease and that's a whole lecture in and of itself.
And then the second question we had are, are increases in SDMA proportional to GFR decreases? Is there correspondence curve just like creatinine. So, we didn't specifically look at GFR in this study, right?
So, but separate from this study, there are some great resources out there that show SDMA, with GFR in terms of the proportion of loss to SDMA, increases and so those are gonna be some foundational studies. There's a, a study by at all in 2014. And then there's a study from Hallet all that's also, I believe, 2014.
Those are all gonna show you those curves, and so, and then there are certainly some more recent works, right, where you'll see that STMA has the same correspondence to GFR decrease that creatinine does, in the literature. OK, that's great. Thank you.
Thanks for your time.
