Hello, everyone. Hope you're well. Welcome to Webinar 8, the final webinar.

I hope you've really enjoyed the previous sessions and had some useful, take-home content that you've been able to use in your, practise. So this final webinar, we're gonna be discussing, acute kidney injury, talking about the diagnosis, and then about the management. So again, we're gonna start with a case example.

This was Jasper, who was a 10 year, 8 month old male neutered Maine Coon cat. And he'd been previously diagnosed with idiopathic inflammatory bowel disease. And that was about 6 months ago, and at that time he'd been started on an immunosuppressive or a relatively high dose of prednisolone, around 2 milligrammes per kilogramme per day, and he'd responded very well to that, and the dose had been gradually reduced.

When he was receiving, about 1 milligramme per kilogramme, which was his current dose, his faeces were completely back to normal. So he was on prednisolone when he presented to us. And he presented with a 3 day history of progressive lethargy, inhabitants, and vomiting.

His referring, practitioner had done a relatively limited biochemistry panel which had, shown moderate to quite marked azotemia. So on physical examination, he was very depressed, he was really reluctant or unable to stand. He had quite marked skin tent, he had dry mucous membranes, he had sunken eyes, so he was estimated about 10% dehydration.

And that, of course, could easily fit with his history of, you know, reduced intake and potentially increased loss. He had halitosis, but actually only relatively mild dental and periodontal disease. He was slightly tachycardic, his peripheral pulses were reduced in quality, his mucous membranes were on the pale pink side, and he had a, a normal CRT.

And then when we palpated his abdomen, he had two enlarged kidneys and he had quite marked sub lumbar pain. So just be conscious, of course, when you're doing abdominal palpation on your, patients that, you know, we do sometimes find. What we think is abdominal pain, but it actually turns out to be lumbar muscle pain or occasionally spinal pain, but the pain in, in Jasper seemed to be focused on those two kidneys which, as I say, were both enlarged.

And then his bladder was, you know, moderately full and non-painful. He had been reported to be urinating at home over the previous 24 hours. And his retro temperature was normal, maybe slightly on the sort of, you know, lower end.

So, as we've sort of been through in some of the other sessions, we think about this problem orientated approach, because there's quite a lot going on in, in Jess, but. So we think about his problems and we try and prioritise those into primary problems or secondary problems as well, and then we actually in those individual lists, or at least the list of primary problems, we try and put them in order of the more likely conditions at the top of the list and the less likely lower down, because then what you're going to do after that, of course, is think about differentials, and then go on to do some testing. So you wanna be doing differentials and testing, of course, for the, you know, more likely conditions.

So, I'm sure you probably came up with these problems in Jasper, acute vomiting, two big kidneys, he was lethargic, he was inappetent, he was dehydrated, and then he had signs that are probably consistent with hypervolemia, so he had an elevated heart rate, delayed capillary refill time, and reduced pulse quality. So he's, you know, in shock, probably hypovolemic shock, probably an additional problem that you could include in there, of course, is the renal, renal pain, but that probably fits with causes of bilateral renomegaly. So yeah, the primary problems are thought to be the acute vomiting and the big kidneys, and then the lethargy and the inhabitence and the dehydration, the signs of shock or secondary to those primary problems.

So we'll think about differentials next, so, you know, consider stopping the webinar and thinking about differentials for the primary problems, so vomiting and bilateral renomegaly. So these are differentials for acute vomiting, and this list is not exhaustive. You will think about other things on there.

You'll probably have these in a, in a different, different order, that, that's fine. So I always split them into primary gastrointestinal diseases, and then other conditions, sort of, you know, extra gastrointestinal diseases, if you like. So the primary GI diseases for acute vomiting, vomiting in dogs and cats, you know, dietary indiscretion should be very high up on their, you know, foreign body interception, of course, you know, your history might help you determine whether that is more or less likely.

Neoplastic disease, you may think, well, that's gonna cause chronic vomiting, and it, it often does, but sometimes we see patients that present with relatively acute onset vomiting. Maybe the tumor's got to a, a degree that's caused obstruction or maybe there's ulceration associated with that tumour. Gastritis, so inflammatory diseases of the stomach and in fact inflammatory diseases of the rest of the gastrointestinal tract, so you'll No, of course, you can see vomiting in patients with, you know, small intestinal inflammatory bowel disease and also those with colitis, large intestinal inflammation.

Gastrointestinal ulceration should be on that list as well. It's a not uncommon cause of acute vomiting, generally drug related, so particularly non-steroidals. And then infectious causes we often have on the list for patients that are vomiting, but they're pretty uncommon, you know, and a cat that's vaccinated and doesn't have access to, say, birds and wildlife, you know, part of feline, part of the virus, and salmonellysis would be very uncommon, and you'd probably expect quite marked diarrhoea, at least with the latter condition.

And then what about other conditions? Well, pancreatic disease is definitely a cause of acute vomiting. Quite tricky, of course, to diagnose, particularly in cats.

Liver disease should be another one, and maybe the acute liver disease, if you remember back to the second webinar, we talked about liver diseases that cats get and. Neutrophilic cholangitis, lymphocytic cholangitis with the sort of big 2. Neutrophilic cholangitis was that acute disease when animals can be unwell, can be pyrexic, not always, can be jaundiced, not always, and they have what's thought to be a ascending biliary tract infection.

So, yeah, their signs can include those of changes in appetite, acute vomiting, and others. Acute kidney injury, of course, should be on the list, diabetic ketoacidosis, peritonitis, you know, think about any drugs or toxins that could induce vomiting, and then don't forget about central nervous system disease because the. Vomiting centre and of course the chemoreceptive trigger zone in the central nervous system.

So most patients with Most patients with, you know, vomiting, secondary to CNS signs have other signs of CNS disease, but, you know, occasionally we see patients that come in to us during presentation of acute vomiting that turn out to have a central nervous system disease like an inflammatory or a, a neoplastic condition. What else should be on there? Well, you know, occasionally there's endocrine other endocrine conditions, so hypoadrenal corticism should be a very important one in dogs.

It's very rare in cats, so it tends to be missed, miss off lists, but those are probably some of the, some of the main ones that you'll be thinking about. And what about differentials for renomegaly or particularly bilateral renomegaly? Well, neoplasia is gonna feature quite highly, particularly lymphoma, that's the more common neoplastic condition of the kidneys that cats will get.

Not always, but often causes bilateral disease. We need to think about pyelonephritis, so usually it it due to bacterial infections, so that can lead to, definitely lead to renal pain, but can also lead to a somewhat enlarged, kidney. We need to think about causes of acute kidney injury.

Various causes of acute kidney injury can lead to renomegaly. Hydronephrosis, so, you know, some animals are born occasionally with hydronephrosis, but it's usually a secondary thing often but not always due to obstruction of the ureter, ureters, you know, it would be. A bit unfortunate for this cat to have bilateral obstruction, at least bilateral obstruction acutely, but as you will have seen cats with, ureteric obstruction, they often have, you know, an obstruction of one ureter historically that leads to hydronephrosis and then over time, you know, end stage kidney, but a But of course, because they've still got a functioning other kidney, they don't present to us necessarily symptomatic and are not asotemic, and then the other kidney becomes obstructed and that's when they present to us with very poor renal function.

Polycystic kidney disease should be on the list, breeds maybe a bit less typical, but you can see polycystic kidney disease in many breeds. Feline infectious peritonitis, definitely a cause of bilateral renomegaly due to sort of, you know, granulomatous inflammation, you know, signalments may be a little bit unusual. And, amyloidosis, we see, very uncommonly, but it is, is on the list of causes of bilateral, renomegaly.

So what would you do next? So have a think about what would you do next. So, you know, we're using this problem oriented approach.

We thought about Jasper's problems, we thought about some differentials, and now we're gonna think about tests to rule in and rule out those differentials. And this is where it comes to having prioritised lists because, you know, we're not going to do an ACTH stimulation test as our first test to look for Addison's as a cause of Jasper's vomiting, because it's very uncommon. But you know, we're gonna be doing bloods to look for evidence of renal disease, which we've already got suspicion, of course, that Jasper has from the refes bloods, but you know, other systemic metabolic conditions and also to look for the consequences of Jasper being unwell for a few days and having reduced appetites, so particularly electrolyte abnormalities.

So yeah, see and biochemistry, have a look at haematology, look for red cell numbers, particularly look at white cell numbers as well, and maybe platelets are important if we're thinking about going on to do any sort of sampling. And then urinalysis relatively critical of course in the patient, you're suspicious might have some sort of renal disease as a cause of the renomegaly. Renal pain and the previously reported asotemia.

So let's have a look at these, and again I'd just encourage you to stop the presentation and just work through, work through them yourself. So, what have we got? We have a very mild hyperkalemia, increased potassium, but, you know, we always have to pay good attention to potassium levels because, you know, slight changes out of the reference interval can lead to quite significant adverse effects, so both low and both high.

The total calcium is slightly low. That's worth, worth noting. When you look at calcium, of course, also look at albumin, because if this, this cat's albumin had also been low, that could be an obvious reason for the low total calcium because about 40% of total calcium that we measure is albumin bound.

So if there's less albumin, there's less albumin bound components, and so that will reduce the total calcium. But in Jasper, the album is, you know, mid-reference intervals, so it's unlikely that accounts for a low total calcium, so we might be thinking about measuring ionised potentially. The phosphate is super high, so that often reflects reduced renal excretion, that could be in the acute context, it could be in the chronic context.

And there is a, you know, moderate to marked azotemia. The creatinine is very significantly elevated in Jasper the urea oddly is maybe not as high as we might expect it. And there's a mild increase in creatine kinase, suggesting there might have been some muscle damage, and that could just be due to, you know, injections, blood sampling, even recumbency possibly, but it's generally not, not significant unless it's in the many thousands, which it's not here in Jesper.

So yeah, how do we interpret these results. So high potassium, we always need to think about artifactual causes, so hemolysis due to, you know, poor blood sampling or difficult blood sampling technique, but we also see hyperkalemia that if there is reduced renal excretion. So particularly in animals with AKI.

There's an aotemia, that might be pre-renal due to dehydration. It's pretty marked due to, if it's just due to dehydration. It might be renal or might be post renal.

Post renal was probably a little bit less likely because the cat's bladder, Jasper's bladder, is not, you know, full to bursting. It's, you know, moderate size, and he's been, you know, urinating until relatively recently. But clinical examination, dehydration suggests that there's definitely gonna be a pre-renal component, but maybe, you know, it's not all down to pre-renal disease, maybe there's a renal component.

And yet, the increased phosphate is suggesting decreased excretion either in acute kidney injury or CKD. And then we talked about the creatine kinase and again talked about the hypocalcemia, which with the protein being within the reference interval is less likely to reflect reduced protein binding. Let's have a look at the haematology, red cell parameters are in the reference interval, but only just, you'll notice, right at the bottom and you'll also remember that we think Jasper's dehydrated.

So if we were to rehydrate him, he would probably become anaemic. So that might be something to keep an eye on over the next, next few days. And there's a very mild neutrophilia, so that could be due to stress, infection, inflammation, combinations of those things.

So, yeah, neutrophilia stress, inflammation, infection, and then we talked about the red blood cell mass at the lower end and we didn't know that the reticular cys were within the reference interval, so, you know. His anaemia could well be if it turns out to be anaemia or rehydration, which it will be, it's probably sort of non-regenerative. So we think about chronic diseases causing anaemia, including CKD, but also bone marrow disorders, but there's nothing necessarily that points towards a bone marrow disorder if we just flip back and have a look at his platelets and have a look at some neutrophils, his bone marrow is producing platelets and neutrophils.

So if you have a single cytopenia, Such as a reduction in red cells as in Jasper. It's very unlikely to be just due to bone marrow disease, at least the common bone marrow disease is like infiltrated disease or infectious conditions of the bone marrow or toxic conditions of the bone marrow. And this is the urinalysis, so the specific gravity is, is reduced.

It's, you know, not quite in that isotenuric range. It's just above that, so it's in a sort of what we might call suboptimally concentrated range. The pH is, quite low, that's a little bit, a little bit unusual.

. And there's lots and lots of protein in there, and then you can see on the microscopy, there's no red cells, white cells, but there were some cockeye scene, so it's very important of course to understand how that sample is taken. So the reduced urine specific gravity of course suggests a renal course to the azotemia, because if it had been entirely due to a pre-renal cause, that urine would have been maximally or the cat would have been trying to maximally concentrate that urine and it would have been above 1030, 10:35 because they're desperately trying to conserve water. So knowing that you've got a dehydrated animal.

And the urine's specific gravity is so optimally concentrated, so it's less than 10:30, then that points towards a renal cause of azotemia because remember the, the kidneys lose their ability to concentrate urine first, and then when they lose a tiny bit more renal functional mass, the animal becomes esotemic. So, looking at the concentrating ability. By way of urine specific gravity is very useful test to identify renal disease.

And yeah, there's discussion about the protein in your ear, it's either glomerulus, so it's been lost across glomerulus or it's post glomerrula. Post glomerul is basically saying, you know, there's a lower urinary tract infection and so bleeding into the, into the bladder. So yeah, what are your thoughts on Jasper so far?

So he's got a history of IBD he's on steroids, he's got this very acute onset history of vomiting and lethargy and anorexia, and he's got big kidneys on examination and painful kidneys, and that we've just been through the haematology and the biochemistry which the pertinent things I guess are. Suboptimally concentrated urine, quite a marked azotemia, hyperkalemia, and also hyperphosphattemia, and then, you know, a suggestion that he probably is anaemic if we were to rehydrate him. So yeah, they can definitely suggest, you know, AKI acute kidney injury because there's an aotemia.

We know from the, the, then the question is, is it acute or is it chronic, and we know from the history it's acute. And the high potassium fits quite nicely with acute kidney injury, whereas of course in chronic kidney disease, you tend to get a normal or sometimes a reduced potassium because you get excessive potassium loss through the kidneys because these animals have got polyurea and so you get a calciuresis, so loss of calcium. And then the acute kidney injury could also fit with, of course, rhenomegaly because we know, we look back at our differentials of rheum megaly, one of those is AKI so kidneys in dogs and cats, tend to become enlarged in acute kidney injury, and then of course, as you know, over time in CKD tend to get smaller and shrunken and your regular.

So it's definitely looking things are lots of things from the history from the barchem, from the, you know, physical examination findings are suggesting that it's, it's gonna be, it's likely he's got AKI. But we've also said there's likely to be a pre-renal component to his azotemia as well, because he's clinically very dehydrated and important, we also think he's hypovolemic. So yeah, what could you do next to try and work out what's, what's going on?

I guess we need to think about the causes of of AKI don't we, to determine any additional tests and particularly what treatment we could use. So we moved on to images kidneys, you know, that's gonna be a reasonably good thing to try and look for things like hydronephrosis, polycystic kidney disease, see if there's any signs of obstruction to his kidneys, see whether there's any architectural changes that could suggest neoplasia, etc. Etc.

And you know, still ultrasound images are of relative relatively little value to you as compared to you actually doing it or looking at it on your own ultrasound machine. But anyway, take my word that these kidneys, you can just make out a measurement there, sort of 7.5 to 8 centimetres were enlarged and there was also loss of corticomoduary differentiation.

And also there was a report of some increased ecogenicity in the sort of area where the medulla meets the meets the cortex. So yeah, big kidneys increased ecogenicity in the area where the medulla meets the cortex, and both the kidneys look very, very similar on ultrasound and they were painful when the images were pressing on them with the ultrasound probe. And our big differentials at this stage were I guess, lymphoma.

FIP should still be on the list, potentially a amyloidosis, although it's very uncommon. Maybe a sort of a toxic, toxic cause. It doesn't look like polycystic kidney disease.

It doesn't look like pyelonephrotis nephritis cause the renal pelvises are not dilated, it's not hydronephrotic. There's no evidence of obstruction. So, you know, infiltrated, infectious causes could be on the list.

So, we don't commonly do FNAs of patients' kidneys, but in the context of AKI it can sometimes be useful, but just be very careful when doing it because, you know, you can cause significant bleeding sometimes. And you don't want to reduce renal function any further. So, you know, GA or heavy stations stop the patient moving when you're putting needles into the kidneys.

And this is one aspirate from the kidneys, so there's always gonna be a lot of background red blood cells. We did check Jasper's coagulation. It's not essential to do, but, You know, it's a very vast, it's a very vascular organ, and we can see significantly bleeding, bleeding occasionally and I guess if we're worried about neoplasia and I'm worried about, you know, concurrent disorders of coagulation like Jasper was in DIC, that could be a reason to check coagulation, but it's, that's probably not essential.

So, yeah, this is cytological image. You can see, you know, red cells, as I say, sort of protinaceous background. There's probably a neutrophil at the, 7 o'clock position, and then there's these big cells which are, you know, irregular in shape and size, got a few granules in them.

Occasionally they're a bit ruptured, difficult to see the outline of them. So they're, you know, single, single cells, . Sat on your sat on their own.

And just just another one here showing that . Cytological image, and sorry, it's slightly out of focus. I don't expect you to interpret these, but if you know you're thinking about single round cells in the kidney, you know, there's very few things, lymphocytes, mast cells, .

Are probably going to be two of the bigger cells that you're gonna be thinking of. And so, you know, they don't really look like mast cells, and we know that cats, you know, a common tumour of the cat's kidneys is lymphoma, so that would probably be, I would imagine be your top, top guess, and they look quite horrible because they're varying different sizes and, you know, maybe these are some that are. You know, sort of a more, a bit more comparable to some of the red cells and things.

So there's a lot of, a lot of variation. Difficult to make out the nuclei, but maybe that one at the sort of 3 o'clock position, you can sort of make out two nuclei, but again, you know, images taken through a microscope are never as optimal as you looking down there yourself. So, yeah, having back to the image interpretation that came back from a selection of images was a heavy background of red cells and then small and intermediate sized lymphocytes, and occasional large lymphocyte was present.

So the smaller lymphocytes are probably that sort of one at the. You know, 66 o'clock or a couple of them at 6 o'clock position. The other ones on this image are probably the intermediate, and then these guys here, these whopping great big things, of course, will be the large, large ones in the game, maybe you can make out the nucleus.

So there's definitely significant anisocytosis there, which is one of the hallmarks of course of . A more malignant disease. So yeah, the, the psychological diagnosis was bilateral renal lymphoma, likely leading to acute kidney injury.

And you'd think, well, tumor's a chronic disease, but of course, lymphoma is not necessarily. You'll see animals that have normal sized lymph nodes one day and then 24 hours later, 48 hours later have huge lymph nodes. So it's exactly the same in kidneys.

There can be a massive expansion of lymphoid tissue which can lead to acute kidney injury. So yeah, what's the prognosis for AKI in general? So not specifically looking at AKI caused by, lymphoma.

Well, it depends on the cause, the extent of damage. So, you know, particularly how aotemic the patient is, whether they've got concurrent diseases, particularly if they've got, you know, multiple organ diseases. The key things, the big take home message about managing patients with AKI is.

You know, you're only going to be able to reduce the urea and cretinine and other uremic toxins by getting lots of urine to flow, so encouraging urine output, so. If you're struggling, or if the animal is not producing urine or not producing sufficient urine, that is a bad prognostic indicator and then so as you'll see in a minute, that's why a lot of what we do is to try and encourage urine production. In, at least in dogs, it's not been brilliant studies in cats, but about 100 cases, of a variety of causes, and I think this was a US study, so it may be very different results to the ones we may see in our UK population.

You know, the mortality is about 60% from death or euthanasia. I would probably say in the patients that we see, and maybe we see a spewed population of quite dramatically affected patients, you know, their, their mortality is sort of relatively, relatively high. The problem is as well that you need to warn owners that if the patient does, the dog or cat does recover, a bunch of them do go on and develop, chronic kidney disease.

But of course they could live for long periods of time with CKD. But of course in Jasper, we need to be cautious about his prognosis, because he's been receiving long-term prednisolone, and we know that in cancer, particularly lymphoma, that reduces the response to other anti-cancer drugs, particularly cyclophosphamide and vincristine. Remember that prednisolone induces that P450.

Drug efflux system and so that is induced to higher levels and then so pumps out some other drugs like cyclophosamyincristine from inside the cells. So, you know, if you have a patient that's currently being treated with prednisolone or other steroids that develops lymphoma, that's probably quite bad news because steroids are usually a great. Anti-cancer drugs, so for a patient to develop cancer on, lymphoma on steroids is a bad thing, and again it reduces the effectiveness of your future treatments.

Yeah how would you manage, yes, but yeah, we've talked about the specific problems. So we're talking a little bit more detail about how we manage, specifically manage API. But again, the important things are fluid therapy and .

Encouraging urine output. How would you treat this cat's lymphoma? Well, you know, a cop protocol would probably be, be sensible.

These cats, though, unfortunately, when they are very significantly aotemic and unwell, are not the best candidates for starting cyclophosphamide at least. So maybe we'd use being Christine, we might use Eisparginase, which are. You know, relatively, milder drugs and cyclophosamide that's likely to make Jasper very very unwell.

So yeah, what about the causes of acute kidney injury? I've sort of touched on these, but it, it's either pre-renal, renal or post renal. And so pre-renal is generally if you have a significantly reduced blood pressure, so that is maybe more commonly seen under anaesthesia.

So we definitely see patients, postoperatively that develop AKI especially if they've been pre-treated with non-steroidals, especially if they've had, you know, blood loss. At their anaesthetic or not had fluid therapy and not had their blood pressure checked. So watch out of it.

Previously very healthy dogs and cats can develop AKI post-anesthetics, so use sensible drugs, monitor blood pressure, support volume if they've got any blood loss, be careful about non-steroidals pre-surgery because of their inhibitory effects on the kidneys being able to auto regulate the blood supply. And then, renal courses, we'll go through some of those in a bit more detail in a minute, but toxins, infections, ischemia, sometimes as part of a systemic disease, so sepsis DIC and then post renal is often obstruction of the . Urethra normally, can be, of course, the ureters as we alluded to, but usually it has to be both of them, of course, occasionally sort of, you know, ruptured, ruptured bladders as well.

So yeah, what about the causes of renal AKI? I would probably say in the patients that we see, renal AKI is probably the most common cause. I suspect that you're probably gonna see, you know, plenty of cats with obstruction to the lower urinary tract, so a post renal cause of AKI.

But you should definitely, of course, you know, be familiar with these causes, as I'm sure you already, already are familiar with many of them. And the nephrotoxins, ethylene glycol and, Easter lily, particularly in cats, grapes, raisins in dogs, probably cats as well. It's just that maybe cats don't tend to eat very many grapes and raisins as compared to dogs.

Non-steroidals, we've already talked about in the context of hypovolemia, but then actually, you know, non-steroidals can, of course, lead to AKI if you're, you know, if you have a patient with osteoarthritis that's receiving them, it's important you tell the owner not to give them if that animal is unwell and not eating and has diarrhoea, vomiting, i.e., could be dehydrated because that's when you're more likely to get AKI.

Yeah, certain anti-cancer drugs, not commonly used, heavy metals not commonly are animals exposed. So ethylene glycol, easter lily, particularly in cats, grapes, raisins, especially in dogs. Yeah, high levels of calcium through whatever cause and some drugs.

Infectious causes the big one in dogs, of course, is leptospirosis, so that should probably be your, you know, sort of number one differential in a patient with AKI especially if they've got signs of current liver disease, stroke damage. You know, your vaccination history and possible exposure will make, leptospirosis more or less likely. FIP, again, can cause AKI.

There's a, you know, relatively sudden and massive inflammatory reaction within the kidneys, and then infectious causes pyelonephritis, which is usually bacterial in origin. And then is ischemic causes, you know, the, as you might expect, so dehydration, shock, talked about anaesthesia, heat strokes are part of a sort of a systemic inflammatory response, and then patients with. Lots of producing lots of pigments, particularly in immune-mediated hemolytic anaemia, especially the intravascular form, can be lots of free haemoglobin and myoglobin, but also bilirubin can do it, it can cause obstructive disease and reduce renal function, and then, yeah, lymphoma we've talked about.

So this is just a study done from a couple of years ago now looking at the causes of, and again, this is freely available. So have a look at this. It's quite a nice article.

I'm going through causes and, clinical findings and prognosis and outcome in dogs with acute kidney injury. You have to sometimes take some of these articles, at least when you're looking at data like this with a. You know, a pinch of salt because it's done in, you know, one population, which is often a referral hospital in one area of the world, so it doesn't necessarily what you reflect what you will see in your primary care practise within the, within the UK, but yeah exchemic causes in their group were, high.

Toxic causes interestingly were relatively, relatively low, but yeah, maybe they don't have very many easter lilies around. Maybe there's not much ethylene glycol in the, in the region where this study was undertaken. A bunch of them again, you still don't understand the cause.

That's probably, that is probably the most common cause that we see idiopathic or or unknown. And then a few infectious, infectious causes, but again, if this was, as this was. Done overseas, you know, maybe infectious diseases that we don't see in the UK.

So, what about the clinical signs, well, of AKI they're, as you saw in Jasper, relatively nonspecific, so anorexia, lethargy, vomiting, diarrhoea, to, to name some of them. And then it's quite variable what the urine output will be in these cases. Some of them have an absent urine production, so that's aura.

Some of them have a reduced urine output, that's probably more common, so that's oligurea, less than 2 millilitres per kilogramme. Per hour, which is the definition of sort of normal urine production. Occasionally dogs and cats with AKA have polyurea, but it's quite unusual.

It's maybe a bit more specific to certain toxins. Some of the, some of the drugs, some of the nephrotoxic drugs, particularly things like aminoglycosides, can cause polyurea. So we tend to see a reduced or an absent urine production, but some animals do have a relatively normal urine output.

There may be other things. They may be pyrexic, they're often dehydrated, their kidneys are normal to enlarged, as we saw in Jasper. And there may be roomy breath, you might have picked up at the start that .

Jasper had some halitosis and so these dogs and cats with of course quite significant uremia develop uremic ulceration in the mouth and secondary bacterial infection. So yeah, look out, look out for that. And this is from the same paper, this is just looking at the clinical signs again in a group of dogs, but again, etiologies are probably different, so clinical signs may well be, may well be different, but again, the non-specific lethargy, anorexia, vomiting, diarrhoea, to start with and.

In fact, you know, in there, they don't necessarily report about, reduced urine production, which is interesting, but as I say, significant numbers of these dogs and cats do get reduced urine production, but they only really focus on PU and PD. So yeah, well I've had the diagnosis, well as we went through in Jasper, it's the acute history. Your clinical examination might help.

Find big kidneys are gonna have increased urea and creatinine. Hyperkalemia is a hallmark of AKI but not every patient with AKI will have hyperkalemia and remember about hemolysis or occasional other causes. Increased phosphate is common, but it doesn't necessarily say that patient has got AKI because of course you see it in CKD.

And they're often unable to excrete hydroine, so they've usually got a quite marked metabolic acidosis. Could be why the acid was a bit urine. And yeah, maybe increased PCV or total protein or the absence of an anaemia and hema concentration.

U in specific gravity is a bit variable if it's just due to a renal cause of AKI then the USG is going to be less than 1030 or 10:35 in a cat. If it's pre-renal, as we said, that animal's going to be desperately trying to, conserve water, so you're gonna have a, you know, an adequately concentrated urine. But some animals have got pre-renal plus plus renal as Jasper seems to have done as well.

It's useful to do a urine sediment examination. It's something that you need to do, unfortunately or fortunately, in practise, rather than send that sample through the post because to an outside lab because these casts and things that you're looking for like in that bottom right, disintegrate very quickly. You might also see calcium oxalate crystals, you sometimes do in ethylene glycol toxicity.

So again, doing a sort of sediment examination is useful. We often do diagnostic imaging and sometimes it helps us with the cause, and sometimes we take FNAs as we did in Jasper, particularly if you're suspicious of lymphoma, so especially with bilateral renomegaly in a cat, maybe with ethylene glycol toxicity, maybe with FIB possibly with or amyloidosis. We don't normally take bigger samples, we don't normally take biopsies of these patients because you can cause significant renal damage, and they've already got, you know, poorly functioning kidneys.

The ultrasound at the top is just showing a a cat that's got ethylene glycol toxicity, so you see this area of quite marked, sometimes, increased ecogenicity between the cortex and the medulla. You do also see that though in in FIP, and then in ethylene glycol, often their kidneys are, have increased ecogenicity and that's just because of course there's lots of, calcium. Oxalate crystals within their kidneys.

There are, so there's an Iris International Renal Interest Society, staging or classification system for acute, acute kidney injury. I've added in this the, values for creatinine that you might be more familiar with in, micromoles per litre, so the standard, standard units. But again, you can sort of, See how these might be categorised in, in different grades.

We don't have good sort of prognostic indicators for all these grades, so it's, they're only somewhat useful. So what, how do we manage these cases? Well, I've sort of stressed a few of these things already, you know, supportive care.

Basically, we're wanting, hopefully, we're allowing time for the kidneys to recover, and we want to prevent additional injury. You know, ideally we want to treat the underlying cause as well, but we want to be very careful about avoiding drugs and general anaesthetics or surgery in patients that got a, acute kidney injury because they've probably lost to a degree, their ability to or regulate the blood pressure. So remember, the kidney's very good at regulating the intrarenal blood pressure despite significant changes in systemic blood pressure, but that ability is, is lost.

Under GA to a degree, particularly when you use non-steroidals, but also in the patient with AKI. So yeah, treat the underlying cause if possible. So maybe lymphoma, leptospirosis would be a good treatable cause and ethylene glycol, you may be able to manage as well, .

When we're treating patients with ethylene glycol, we all we aim to try and do is stop the further production of the toxic metabolites that occur when ethylene glycol is broken down. So it's not ethylene glycol per se that causes the AKI. It's the toxic metabolites like the acids and then the calcium oxalate that forms.

So we tend to use Things that inhibit the breakdown of ethylene glycol, things that inhibit alcohol, dehydrogenase, which is the enzyme that breaks ethylene glycol down, so. You know, there's things like 4 methylparazole, which are relatively selective. You can also use alcohol, so, you know, off the shelf alcohol that you've got purer the better, of course, and there's definitely various protocols for using that, but I would encourage you to speak to the, veterinary poisons Information Service for any cause of toxicity, but, you know, this, this one will be a suitable, suitable one to talk to them about.

So then they also need IV fluids and again it's about getting urine output and treating complications. So these patients can be hospitalised for several days to longer, so you sometimes struggle with veins, so it could be one that you put a central venous catheter in if you've used those before, because it allows you to give lots of fluid, different medications, take blood samples from the catheter and you can usually leave it in for the duration of hospitalisation. So in a patient like Jasper that we think is hypovolemic, we're gonna want to try and stabilise with bolus or bolus of fluid therapy.

We're gonna use saline, lactated ringers, don't add potassium and things in there. If that patient happened to be hypokalemic, obviously, Jasper's mildly hyperkalemic, so we're definitely gonna want to avoid adding potassium. Lactated ringers, Hartman solutions is a little bit of potassium, but that, but that doesn't matter.

And we're gonna use tables like this, which is just taken from a, you know, critical care ECC manual to sort of for us to try and guesstimate how much fluid to give these animals. So you can see it's quite subjective, you know, mild, moderate, mark hyperalemia. So you're looking at the compensate your responses to anaemia, so in a sorry, to hypovolemia.

So in a patient that's hypovolemic, of course, you'll get activation of the systemic. Nervous system, you'll get increased heart rate, you'll get, vasoconstriction to the periphery. So you'll see things like paler mucous membranes, and, you know, reduced peripheral pulse quality.

So, you sort of look at some of those. Things, but the most important thing is that you identify based on these sort of parameters whether that patient could be hypovolemic and then you know to give it some fluid bolus and we would often start with 10, maybe 20 millilitres per kilogramme over about 30 minutes. And importantly, you know, when you're giving fluid at higher rates and you're probably used to just, you know, make sure they don't have any cardiac disease, that will be a time not to use it, .

These higher rates, but, also, yeah, monitor the respiration and listen to the thorax for any signs of pulmonary edoema. And then basically, we may need to give more fluid bolus because what we're wanting to do is to try and normalise these parameters, you know, get the heart rate reduced, pulse quality should come back, CRT should improve, mucous membrane colour, etc. But of course the caveat is that there's other reasons maybe for a tachycardia like in Jasper.

He's a cat, so he's gonna have higher heart rate, but also, you know, he's, he's in pain. So once you think, so, you know, big take home, look for patients that you think have got a fluid deficit and decide whether they've also got a circulating fluid deficit, whether they are, hypovolemic as well, and then give boluss to try and restore those parameters. And then once we've done that, we think about, you know, the fluid therapy going forward.

So we think about the maintenance requirements and then we think about the hydration loss and any ongoing losses as well. So hence why your fluid therapy plan isn't static, it's probably gonna have to change over, over time. The animal's hospitalised.

So just to give you an example on a, I don't know, let's use a, let's use a Jasper, say Jasper's 5 kilogrammes, and we said he is 10% dehydrated. So actually he's deficient in 500 millilitres of fluid. That's what he's lost over the previous days and also, you know.

Deficiency from reduced intake. So if you just, you know, get them in and hang a bag of fluid and give it a rate maintenance for a bit over, you're never even going to replace the amount that's lost. And then you need to decide how quickly and so, you know, the quicker the better in a way, but the quicker you give it, the more likely you are to get, you know, over hydration, pulmonary edoema.

So, you know, in a patient like Jasper, we might decide to give it over 8, 12 hours in a patient that's, You know, quite stable, and we need to just replace their deficiency. We may be giving it over 24 hours. So really critical that you try and guesstimate the dehydration based on the parameters that Jasper had, which were abnormal like the skin tint and, you know, the mucous membrane.

Tackiness and the position of the eye is very subjective, but you know, just try and guesstimate something. If you guesstimate at 7% and it actually turns out to be 5%, that doesn't matter or vice versa. Weigh these patients, at least twice daily to make sure your fluid therapy is sufficient and also monitor for fluid retention and overload, which is particularly important in a patient like Jasper that we're worried about his, urine, ability to produce urine.

The other thing is to try and monitor urine output. You know, the crudest way is to just palpate the bladder or try and collect the urine, but that's very challenging. So the best thing to do is put an indwelling catheter in so you can monitor the rate, which should really be, you know, more than 2 mL per kilogramme per hour.

Because if you're not getting that rate, you need to do something about it, and you might not be able to very accurately at all assess urine output just by palpating bladder or trying to, you know, measure urine from a dog in a bowl outside or collect it from the, from the bedding. So when you're collecting the urine from these patients, or any patient you've got a urinary catheter in, ideally have a closed drainage system because it will reduce the chances of them developing an iatrogenic urinary tract infection by you having to, you know, attach syringes onto that urinary catheter periodically to to empty it. So yeah, closed urine collection systems are good.

So, you know, if you're given lots of fluid therapy and that patient with AKI is still not producing more than 2 millilitres per kilogramme per hour, you need to do something about it, because again, the key is getting these patients to produce urine so they can excrete those renal toxins. And so we reach sometimes, often used to, maybe less so nowadays, but we still do reach for diuretics and the common one that we reach for because it's on the shelf and we know how it works and what the doses are is furozamide. We maybe give Ebolus and then we might keep it going afterwards with a continuous rate of fusion.

If there's no response to a sort of a standard bolus like 2 milligrammes per kilogramme per . 2 milligrammes per kilogramme, you know, we might go and, might go and double, double that. And, but the problem is that, there's been some more recent sort of, studies in, in humans, that have looked at.

Roamide administration in patients with AKI and yeah, these are human patients that may be different causes and things, and suggested that unless you give it very quickly, it doesn't make that much of a difference. We must say still give it because we don't have lots of other options. The other option you could consider is a osmotic diuretic, which is basically a You know, a big molecule, you're giving glucose or dextrose or Manitol, they cause they get filtered across the glomerulus and they drag water with them, so smotic diuretic.

So occasionally those can be useful as well. Again, you're just trying to get urine to be produced. Dopamine is often mentioned in in textbooks, but we wouldn't generally nowadays use, use dopamine.

It's at sort of lower doses, it increases renal blood flow and can change GFR but at higher doses it's bad because it, it reduces renal blood flow. But there's sort of meta-analysis from studies to suggest that it doesn't improve survival in human patients. You probably won't have it on your shelf.

You have to give it as a continuous rate of fusion, so it's quite challenging to do, so we don't use it anymore. So again, just making sure you've gone back and made sure you're giving enough fluid to that patient is probably the the most common thing where people go wrong. You know, so don't start using diuretics and things before you make sure you give them enough fluid.

Other drugs that have been suggested in the literature, tebutyle, diltiazem, don't have very much experience with them. There was a study done a few years ago now looking at AI, secondary to leptospirosis, and, using, using diltiazem, and it seemed to, seemed to help these patients. Other things you might need to do if they're significantly hypokalemic, and particularly if that hyperkalemia is, causing cardiovascular disturbances.

So if it's causing a bradycardia, or if it's causing significant ECG abnormalities, arrhythmias, or if it's causing evidence of reduced cardiac output, which it can be, without actually showing any, you know, rhythm abnormalities. That's the time to try and manage, manage that. This was an ECG from a patient with potassium of 8.5 and.

You know, there's a bit of a sinus arrhythmia, but maybe you could sort of struggle to see a P wave on there, . And then does funny things, T waves as well, so they tend to get reduced P wave amplitude and then atrial stands still. They also get bradycardia and then things, as I say, happen to the QRS and T waves.

But there's a bit of an individual response to hyperkalemia, so you don't necessarily treat a laboratory value, again you treat the patient that has adverse consequences to the hyperkalemia. Calcium gluconate is good because it's a cardio protective drug. You could give things like insulin, or sorry, you could give things like glucose, plus or minus insulin, I would only ever give glucose and then rely on the body producing insulin, occasionally buy carbonate, but for me, fluid therapy is the main thing.

Calcium gluconate is a cardio protective drug and then possibly glucose. These dogs and cats with AKI can have really significant metabolic acidosis. We extremely rarely address that directly.

We normally, you know, sort out perfusion. You know, get kidney function to return again, and that sorts out the metabolic acidosis. But if you, did want to do something, you could work out their bicarbonate requirements and give them some bicarbonates can make a difference to them, but you may well not have bicarbonate on the shelf or be used to using it like we, we are very uncommonly use it.

The other thing you could do is peritoneal dialysis, it basically buys time. For the kidneys to return to normal, normal function. So if your fluid therapy isn't effective, your diuretics are not effective, you know, the azotemia persists, you're not able to get urine to be produced sufficient volumes, you're getting rid of those ureemic toxins, then this is probably the only thing that remains.

And again, it just buys you time until the kidneys can recover, which they do in patients. We just, unfortunately, because This has got quite poor availability, you know, we, we don't have that option in many patients, but, you know, it's either hemodialysis or peritoneal dialysis. Hemodialysis, of course, very limited availability in the, in the UK really, only one centre, undertaking it and it comes at considerable cost.

Occasionally we do peritoneal dialysis, so that's basically using the peritoneum as the dialysis. Membrane, whereas in hemodialysis you're having a dialysis membrane in the machine for uremic substances to cross and be removed by the machine. In peritone dialysis we're working on the assumption that diazebia that compounds that can pass across the peritoneum, we can then remove them in the fluid we've put in the animal's abdomen.

So it's indicated in patients that have got You know, acute kidney injury and they're not producing urine or not sufficient urine, with things that again we think that we can just buy a bit of, buy a bit of time until the kidneys, kidneys recover. So, you know, use dialysis in patients with leptospirosis with ethylene glycol toxicity until we can get on board on top of their disease, or again, until we can get, urine to be produced. These are not patients, of course, with CKD that you should be doing dialysis in.

But it's quite, it's quite time consuming, it's quite costly, it's challenging to do. You basically put either a, you know, an indwelling or an intermittent catheter, occasionally needle, but catheter's far better into the dog or cat's abdomen, and you instil fluid in there, the dialysis fluid, which you can make yourself from. Lactated ringers and adding some dextrose to it, and you leave it in for, you know, a period of time, half an hour, 1 hour, and then you remove it.

But you probably have to do this, you know, more than once, 2 or 3 more times a day. And, so it's quite time consuming. Animals get stressed, you have to heavily state them.

You know, ideally you're gonna put a peritoneal catheter in that you can just, you can just leave in. But have a look in the textbook about how to do it. The, BSAV procedures guide that I co-authored has got a section on peritoneal dialysis going through the technique and equipment and things that you need, but it can save lives because it just buys that bit of time for the kidneys to return to normal function.

Well, about the prognosis, well, as we alluded to before, it depends on the, you know, extent of damage and concurrent conditions and things, and again, as I've hopefully stressed you, the absence of urine or the reduced urine production is a, you know, a significant negative prognostic indicator. That's why all we're doing is really trying to get urine production, critical things again I just. To ensure you have, you're giving them adequate fluid, so not only the circulating volume, but particularly for that, you know, deficit, the amount they're dehydrated, get on top of fluids is the biggest mistake that that people do or not getting on top of fluids, and then occasionally using the, the diuretics afterwards and possibly if you, you know, owners can afford and you've got the skills and expertise and time doing peritoneal dialysis.

And then we said before, you know, mortality is relatively high, so you need to warn owners and a bunch of these animals that do survive, go on to develop chronic kidney disease. Unfortunately for Jasper, because we felt the prognosis was relatively poor, particularly because of the pre-treatment with steroids and in developing lymphoma on a, you know, anti, good anti lymphoma drug. Yeah, unfortunately, he was, euthanized.

So yeah, thanks for listening to this webinar and thanks for listening to all the other webinars. And yeah, again, I hope you've found lots of information useful that you can take back to your practises. So yeah, bye.