Hi, and welcome everyone to tonight's webinar. I am Doctor Becky Mullis and I'm a veterinary nutritionist with Hill's Pet Nutrition. And I'm really excited to introduce tonight's webinar with Doctor Jean Hall.
So, the webinar is Nutritional Interventions in Early Feline Chronic Kidney Disease evaluating the Evidence. We have a lot of great material to cover tonight, so, really excited to have so many people already here on the webinar. So, just a few housekeeping things to mention before we get started.
If anyone has questions for the speaker, please use the Q&A box. That way we can collect all of the the questions as we go along, and, I will make sure to ask them at the very end of the session. If there's any other comments or things you'd like to mention, please use the chat box.
Now, I've already mentioned, our speaker tonight is Doctor Jean Hall, but I'll, for those of you who don't know her, I'll do a quick introduction. So, Doctor Jean Hall is a professor in the Department of Biomedical Sciences at Oregon State University. She received her DVM from Washington State University and completed a small animal internship at Angel Memorial Animal Hospital.
Her residency was at Colorado State University, and she is board certified Small Animal internal medicine. At Colorado State, she earned a PhD degree in physiology and then completed a postdoctoral fellowship in clinical nutrition and lipid metabolism at the Oregon Health Sciences University. Her research focuses on health benefits of dietary supplements, specifically their effects on renal biomarkers, metabolomics, and the microbiome.
So, Welcome, Jean Hall, and we're very excited for your topic tonight. I'll hand it over to you now. Yeah, thank you so much, Becky.
I'm really excited to talk about nutritional interventions in early feline CKD. I have a lot of evidence to go through, so, I counted up about 20 studies, so we'll cover some in more depth than others, but I'm excited to share that with you. I wanted to start off and acknowledge Hill's Pet Nutrition, for many of these studies are performed at the Pet Nutrition centre, and I also wanted to say a special thank you to Dennis Jewell.
He's my long-term collaborator. He was senior nutritionist. He's recently retired but still working, as it seems like we all are.
So, nutritional interventions play a crucial role in managing chronic kidney disease in cats. A commercial renal diet is the most prescribed management approach, but as we can see from these five studies here, one of them is actually in dogs, but up to 60% of cats with chronic kidney disease aren't eating renal food, so we have a lot of room for improvement there. Proper nutrition can significantly impact the progression and quality of life in cats with CKD.
The therapeutic goals, in early stages, stage 1 and 2 CKD aim to slow the progression of CKD and preserve, remaining kidney function, so that we can prolong survival. In doing so, we prevent uremia. We need to address nutritional needs.
With a decrease in appetite in many of these cats, it's important to consider whether there's, there's adequate intake of macro and micronutrients. Especially, we need to increase their caloric intake and supply sufficient. Calories to maintain body weight, and to provide the amount of essential amino acids that they need.
And of course, maintaining hydration is important, making sure that water intake is adequate, and strategies to increase water intake should be considered. So my outline for today, we want to look at supporting muscle mass and food intake in part one. And part two, we'll talk about nutritional interventions to modulate the gut microbiome, and then renal foods and calcium homeostasis, and then we'll sum up on key findings and recommendations.
So first, on food intake, we'll talk about a prospective study where we looked at the influence of dietary ingredients on renal health in cats. And kind of the key point here was that cats with iris stage 1 and 2 CKD maintain their body mass and lean muscle mass when they're fed foods having increased caloric density and concentrations of carnitine and essential amino acids. So that kind of gives the key point away.
As a little bit of background, do cats with iris stage one benefit from feeding a renal protective food? Well, we know that they do if they have persistent proteinuria or hyperphosphatemia. And then in a study that we did and published in 2016 with client-owned geriatric cats in early stage, I was stage one CKD that didn't have proteinary or hyperphosphatemia, when they were fed a renal protective food, they were more likely to demonstrate stable renal function compared with cats that were fed the owner's choice food over a six-month period.
We've also shown that ageing in cats is associated with a loss of lean body mass, and that as GFR decreases with age, serum creatinine can also decrease because of the loss in lean body mass, but SDMA increases with a decrease in GFR. We know that cats with CKD have a reduced ability to maintain body weight. And we know that feeding a renal protective food to cats with later stages, so iris stage 2 or greater CKD, is considered the standard of care.
This was shown or based on two studies. The first, in 2006. Where, Ross et al.
Showed that feeding a renal protective food was better than feeding just adult maintenance food for minimising uremic episodes and kidney-related deaths in cats with the more advanced stage 2 or 3 CKD. And then in another study published in 2005, feeding CKD cats any of several seven commercial foods resulted in longer medium survival times. On average, it was 16 months, but some of those commercial foods, they survived 23 months.
Compared with the cats that were fed conventional foods, their means survival was 7 months. So, in this particular study now, to provide prospective clinical trial data, we looked at a commercially available renal protective food and fed it over a six-month period. It had controlled protein and phosphorus levels, increased caloric density, enhanced essential amino acid concentrations.
We added L-carnitine, fish oil, antioxidants, and it had enhanced palatability as well. The control food had similar protein concentration, but a different composition. Again, it was a prospective 6-month feeding trial.
There were 28 cats with iris stage 1 and 2 CKD and daily food intake, weekly body weights, serum and urine parameters that were assessed, and DEXA measurements were made at baseline and and 13 and 6 months. And it was hypothesised that the cats consuming the test food would maintain or improve their status of Renal biomarkers and also would consume more calories and maintain body weight and lean body mass compared with cats fed that control food. So here's the baseline demographics.
The cats were 9, 10 years old. Most of them were iris stage 1, 12 and 11, a couple of stage 2 in each of the groups, but otherwise, there was no significant difference between their lean and fat body mass and other parameters. The two foods that were fed, the control food was a royal canine renal support dry food that had a protein level of 6.65.
So here's control food. The test food was Hill's prescription diet KD feline, very similar protein levels. They met the AFCO minimum of both foods did of 6.5 grammes per 100 kitcals.
The energy levels were different in that the test food had more calories provided per kilogramme. The phosphorus levels both were a little bit lower than the AFCO minimum of 0.125, .
The test food was 0.105 and the control food was 0.118.
Now, here are the results. 20 cats completed the study, 9 control cats, and 11 eating test food. The cats consuming the control food, which is the light grey, lost body weight over the six month period.
So if you look at the light grey bars, they actually go down about 13%. That was significant. 0.001, the cats consuming the test food increased their body weight, about 5.8%.
Those are the dark black bars. And if we focus specifically on lean body mass, the cats consuming the control food lost lean body mass, about 11%, whereas there was no change in the cats consuming the test food. If we look at caloric intake, the cats fed the test food, these are the dark black bars, consume 23% more calories.
That wasn't because they were offered more calories. The food was more calorically dense. So compared with the test foods, cats, I'm sorry, compared with the cats fed control food, they ended up consuming more calories.
And if we focus on one of the more limiting amino acids, essential amino acids, 3anine intake for cats over the six-month feeding period, and group them according to the total 3anine intake as low or adequate, and then look at change in lean body mass, we see that the cats that were consuming lower amounts of 3anine actually had a much greater loss of lean body mass than the cats that were consuming adequate amounts of 3anine. If you look at renal biomarkers, we'll just focus on creatinine. Cats consuming the control food.
Had a faster increase starting at about 1.39 over to six months, 1.64 in serum creatinine compared with the cats consuming the the test food.
It went from 1.35 up to 1.53, so that was significant at 0.0004.
So the take-home message from this study was that Iis stage 1 and 2 CKD cats that were fed food with increased caloric density and increased essential amino acid concentrations had an increase in body weight, stable biomarkers of kidney function, and maintained their lean body mass. So a greater intake of essential amino acids in the test food. Again, that was a combination of increased consumption, and also the 3anine levels were about 33% higher in the test food compared to the control food, resulted in the cats consuming the test food having adequate intake of all amino acids, including 3anine.
Again, it was the limiting amino acid in the food. So it's adequate intake of essential amino acids, not dietary protein, that was correlated with maintenance of lean body mass in these CKD cats. And that goes along with the nutritional truth that it's the actual requirement is met by food intake, not by the concentration in the food.
OK, so that's my part on food intake and maintaining muscle mass. The next part is on how the food interacts with the GI tract and the microbiome in cats with CKD. And this overview just shows that cats ingest food that contains the nutrients, they undergo host digestion, and break that food down into the monomeric units that are then available for absorption by the host.
Nutrients that aren't utilised are available for the microbes to digest with the same processes and make the same monomeric units, and those then can be used for microbial absorption. Any nutrients that are left over, particularly the carbohydrates and proteins, are available for microbial fermentation. And then the postbiotics or things that are produced can have an effect on the local gut health, or they can be absorbed by the host into the systemic circulation and have effects at far distant sites.
We know that food plays a significant role in defining the composition and metabolism of the GI microbiome. And from a recent study, we know that dietary protein and carbohydrate levels Affect the gut microbiota and clinical assessment. Now, this is gonna be a study where we look at healthy adult cats, just to show how protein and carbohydrate can affect the gut microbiota and the products that they produced.
So, in this study, 3 foods were fed with different protein to carbohydrate ratios. Again, it's healthy cats, there were 30 healthy cats. The foods had 28% protein dry matter, 35% or 55% corresponding to 7.3, 9.1%, and 13.4 grammes of protein per 100 kilocalories.
And we'll just jump right to the visual that demonstrates the difference between the extremes or the, the P55 food and the P28 food. And what we see is that when the cats consume the Highest level of protein, or 55% protein on a dry matter basis, compared with the lowest level of protein or 28% protein on a dry matter basis. Even though this section here is the small intestine, even though there was higher protein digestibility in the small intestine, so 97.6% versus 94.5%, more, Well, actually, less protein entered the gut in the cats on the higher protein foods, so 0.21 grammes per kilogramme body weight versus 0.25 grammes per kilogramme body weight.
But what's produced, so this is large intestine, what's produced over here in column D, Showed that the cats consuming the highest level of protein, the gut microbiota exhibited a higher mucin glycan foraging and amino acid metabolism, leading to a higher pH, higher amounts of branch chain fatty acids, and higher ammonia levels. This was likely due to Less availability of carbohydrates or fibre sources, so that they actually use the mucin and gut barrier as a source of fermentation without having the carbohydrate availability. Whereas the cats that were on the lower protein food, the availability of carbohydrate sources led to microbial sacrolytic fermentation, lower branch chain amino acid concentrations, lower pH, lower ammonia concentrations, and no impact on mucin degradation or gut barrier function.
So, in conclusion, when healthy cats consume the highest level of protein, their stool contained higher ammonia and branch chain fatty acid concentrations associated with a higher pH, and that was likely due to the lower availability of fibre and carbohydrates. So, greater proteolytic activity produced metabolites that are potential uremic toxins. And so the amount of protein in the food is important not only for phosphate considerations in cats with CKD which many of us think about limiting phosphate concentrations, but it's also important for microbiome concentrations.
So, too high of a protein concentration in the food may negatively affect the health of CKD cats, even with controlled phosphorus levels by increasing the BUN, the protein, and the concentrations of microbial uremic toxins. That's been shown in a couple of studies there. And too low of protein and phosphorus levels, this was Shown by Schaff et al.
In 2021 may negatively affect the health of CKD cats by causing hypercalcemia, increasing the plasma concentrations of FGF 23 and SDMA, and by increasing the frequency of urolithiasis. And we're gonna talk about some of those things in more detail in the end of the talk. So, what do we choose?
This is a busy slide, but the optimum concentration of protein and phosphorus from our studies appears to be a protein greater than 5.9, which is what they had in the SHL study, but less than 8.1.
We had three studies in this range showing good results. So, 6.95, 6.5, and 6.69 grammes per 100 kcals, which is right around the AFCO minimum protein of 6.5 grammes per 100 kcal.
It needs to be high quality protein with essential amino acids present at at least 150% of the AFCO recommendation for minimum ratio to energy. And it needs to be calorically dense. That's very important to maintain body weight and lean body mass.
The phosphorus needs to be greater than 0.08 grammes per 100 kcal as shown in the shelf study, and probably around the AFCO minimum of 0.125 grammes per 100 kau, with three studies near this range showing good results.
So 0.105, 0.131, and 0.105 grammes per 100k.
OK. I wanted to just mention a couple of, of, of reports where we looked at how fibre modulates the gut microbiome. And in particular, we're looking at the Cas with CKD and how it altered the response of the plasma metabolites and the faecal metabolites, and also the faecal microbiome or the bugs in the GI tract.
In response to dietary fibres. So, the objective was to determine the effects of feeding dietary fibre types to healthy cats and cats with CKD on the plasma metabolism, the faecal microbiome or the bugs, and the faecal metabolism or what they produced. These treatment foods contained 0.5% betane, 0.586% oat beta glucan, and either 0.407% short chain fructo oligosaccharide, or I'll call it POS from now on, or 3.44% apple pomus.
And both foods had betane and oat beta glucan because previous studies had shown that that combination results in the CKD cats having a higher body mass. Looking at the plasma metabolism results, we saw that health status does impact the effects of the dietary fermentable fibres on the plasma metabolism. So, for example, the CKD cats had increased accumulation of the uremic toxins such as the indo sulphates and urea in their plasma.
And the short chain phos fibre sources had significant benefits in reducing many of the mic toxins in these CKD cats compared with apple palma. They also had a benefit of improved oxidative and inflammatory status while on the short chain hoss. Which differs from the healthy cats because they had an improvement in status with apple pumice, which kind of brings up a point that the importance of choosing optimal fibre sources may be different based on the overall health status.
When we looked at the faecal metabolo, there were relatively few metabolites that differed in the faeces between healthy and CKD cats at baseline, and feeding both fibre sources, both foss and apple pomus, caused the faecal metabolites to change from baseline, such that fibre has a much bigger impact than the overall disease status. And interestingly enough, the changes in the faecal metabolite concentrations did not routinely reflect the metabolite concentrations in the plasma. OK.
So now I wanna move on and talk about butane and prebiotics. Betae is an interesting mechchemical or structure. It, it's a low molecular weight compound.
I've got its chemical structure here in the corner, small molecule. It accumulates in the cell cytoplasma in order to protect the structure of proteins and enzymes. And the primary role of betane in the kidney is osmal protection of cells in the medulla.
So betane can bind a considerable amount of water, and that hydration then protects. The cells that are located in the medulla, and it stabilises their proteins, and otherwise cell dehydration would result in protein denaturization and loss of their biological activity. So, higher levels of betane are advantageous because they increase the tolerance of cells to unfavourable conditions.
Now, the most common foods with betane are beets, it sounds like betane, but also spinach and oats. Betane also supports methyl donation reactions to provide protective biochemicals in stressful conditions. So, es adenosyl methionine is a methyl donor in nearly all the methionine or methylation reactions that need methionine in the body.
And so we can say that betae enhances one carbon metabolism. So, it's a methyl donor. It normally comes from choline.
Choline, is transported into the mitochondria. It undergoes a two-step process and first being converted to betane aldehyde by choline dehydrogenase, and then to betane after the aldehyde is oxidised. And then betane is available to donate a methyl group to methionine, so it's important in methionine metabolism.
It actually restores homocysteine levels and maintains that es adenosyl methionine es adenosy homocysteine ratio. Now, if choline dehydroxyase is limiting or not enough betane is being made, then supplemental betane provided through the diet could provide a benefit. Prebiotics, so we are, we're adding betae and prebiotics.
We'll talk about prebiotics next. They are non-digestible fibres that are fermented by microbes in the large intestine. Microbial fermentation in the large intestine or the hindgut of cats is important for feline health, even though we think of cats as an obligate carnivore.
These fibres are carbohydrates, but they're not digested by enzymes in the small intestines, so consequently they pass to the large intestine where they undergo microbial fermentation. Fibres can be classified according to their physical chemical properties as far as their fermentability, their solubility, or their viscosity. And there are short chain carbohydrates that are resistant to small intestinal digestion, that are soluble and highly fermentable, so short chain, highly fermentable fructo oligosaccharides, and then there are longer chains, carbohydrates that are resistant to small intestinal enzymes that are highly fermentable that include the pectins, inulin, dextrins, glucomonin.
But also some that are partially fermentable, and in that category would be the beta glucans. Most of the studies with dietary fibre and kidney disease have been performed with highly soluble and fermentable car carbohydrates or fibre. So how does fibre work?
It, we say it decreases the level of uremic toxins in the blood, and it does this by promoting the gut microbiota shift towards sacrolytic bacteria. That increases short chain fatty acid production. And these short chain fatty acids contribute to kidney health by reducing the stimuli to systemic inflammation and improving the intestinal barrier.
And both modulate the immune system and the anti-inflammatory response. So, at least in humans, adequate dietary fibre intake is able to correct the CKD associated dysbiosis, reduce gut-derived uremic toxins, inflammation, and oxidative stress, which improves the metabolic profile and slows the progression of chronic kidney disease. Dietary fibre simultaneously reduces the growth of proteolytic gut bacteria, which reduces the gut-derived uremic toxins, inflammation, and oxidative stress.
It also increases stool output by a laxative effect. Which increases excretion of gut-derived urinic toxins in the stool. So in humans, at least, with CKD dietary fibre retards the progression of CKD through mechanisms regarding, or that regulate metabolism, immunology, and inflammatory processes.
OK, what about in cats? Well, in cats with CKD we know that they have decreased richness and diversity of the faecal microbiome compared with healthy cats. That was shown by Summers et al.
In 2019. The microbiome, however, may be more meaningfully described by how it functions rather than just the categories or taxonomic compositional makeup. So we can predict the metabolic capacity based on the metabolites that are produced.
And you can detect these metabolites in circulating blood or plasma samples. Now, the International Scientific Society on the Association of Probiotics and Prebiotics defines a postbiotic as a preparation of inadequate microorganisms and or their components that confers a health benefit on the host. I'm mostly interested in their components.
They're the metabolites that are produced by this microbiome that can affect host function. And in that category, are the uremic toxins. So, the uremic toxins are postbiotics that impact kidney health, and that, those include indoxyl sulphate, Pres cell sulphate, and phenyl acetylglutamine.
And just to kind of show how this works, these gut bacteria metabolise tryptophhane, for example, into indole, or phenylalanine into phenol, or choline into trimethyl amine. And then these uremics solute precursors are absorbed across the gut epithelium into the bloodstream, and they circulate until they reach the liver, and they're removed by conjugating with the sulphate. So, Indo gets conjugated with a sulphate to make indoxyl sulphate.
Pheno becomes phenocrystal sulphate. Or they can be oxidised in the liver, so trimethylamine can be oxidised into trimethylamine and oxide. So, these are the uremic toxins, and they negatively correlate with kidney function.
That's been shown for endoxyl sulphate, precreas cell sulphate, and phenylcetyl glutamine, and overall, they contribute to endothelial damage and oxidative stress. So, using endo oxid, As a, or in doxyl sulphate as a uremic toxin example, we can see that they compromise all components of a healthy kidney. They Cause fibrosis of the tubular interstitium.
They cause senescence of the proximal renal tubular cells, dysfunction of the vascular endothelium. They cause vascular smooth muscle cell senescence, and all of these lead to chronic renal hypoxia and CKD progression. So, next, I wanted to present two research studies that demonstrate the benefits of betane and fibre in cats with CKD.
The first study, feeding cats with CKD, food supplemented with betane and prebiotics, kind of give it away here, increases total body mass and reduces uremic toxins. So it's these uremic toxins, we're looking for ways to reduce those in cats with CKD. And just as a background, we wanted to evaluate the effects of feeding betane and prebiotics on body weight in both CKD and healthy cats.
Again, we know that cats with CKD have a decreased ability to maintain their body weight, and that ageing in cats is associated with loss of muscle mass or sarcopenia, and lean mass decreases with age in otherwise healthy cats. We know that a decline in kidney function may be associated with increased oxidative stress and inflammation, and food is a major source of oxidants, and food can be modified then to affect changes in oxidant burden. So this study design, we had 7 CKD cats.
They were fed pretrial food for 28 days, and then randomly assigned to control food or test food. The control food was the same as the pre-food, and each of these foods was fed for 8 weeks, and then we crossed over, so it's a crossover study designed to the opposite food. So 7 cats, these were the CKD cats.
In the second study, there were healthy cats, and I was 8 in each group. They received controlled food or test food for 8 weeks, so no crossover. They just received controlled food or test food for 8 weeks total.
Blood and urine and faecal samples were collected at the end of each feeding period for the CKD cats and monthly for the healthy cats. We monitored body weight and composition using DEXA at baseline and then after each feeding period. So, just to look at the composition of the pretrial food, which again was also the same as the control food, and the test food that was supplemented with betane and prebiotics.
The protein levels are, are the same. It's about 6.86 grammes per 100.
K cow, the phosphorus levels were the same, right on the AFCO recommended minimum of 0.125 to 0.127 grammes per 100 ca cows.
Otherwise, the foods are pretty much identical except the test food has betane and prebiotics. So here are the outcomes. The test food with betane and prebiotics increased total body mass.
It was significant at 0.004, without a significant change in food intake. There was a decrease in indole compounds in the urine and an increase in faeces, and the plasma concentrations of the indole compounds were negatively correlated with kidney function in the CKD cats, indicating a potential benefit of consuming the test food.
In the healthy cats, there was no change in body mass for the healthy cats. They did have a decrease in plasma precreasol sulphate, and that was quite significant, and they had increased levels of DHA and EPA even though both the control and the test foods had similar concentrations of these long chain fatty acids. So that was an Puzzling thought at first, but looking back to some prior studies, where dietary betane was fed and shown to interact with very long chain PUFAs, this was a previous study, so it was an interaction study.
There were 6 foods that were used to evaluate the interaction of betane and N 3 PUFA. So control food, control food plus flax, and then a control food plus fish oil compared to a control food plus betane, a control food plus betane and flax, and then a control food plus betane and fish oil. And in this study, it showed that betane interacted with the fish oil to dampen a diet induced increase in arachidonic acid, while potentiating the increase in DHA that occurred with increased DHA intake.
So, thinking about this study, it made sense in the healthy cats in our prospective study that they had an increase in DHA even though there was no difference between the test food and the control food. That was the betae interacting with the The N minus 3 fatty acids in the food. Also in this study, the combination of betane and fish oil reduced renal toxin 3 and doxyl sulphate levels, again, supporting what was seen with the healthy cats in the betane and prebiotic study.
So that suggests a positive effect on the gut microbiota. So the addition of betane and prebiotics to the control food formula increased total body mass in CKD cats, and it's thought that's occurring because betane supports methyl donation reactions to provide protective biochemicals and is useful in energy metabolism. It's also an osmotectant of cells, and We can see that with plasma concentrations of indole compounds being negatively correlated with kidney function, indicating a benefit of consuming the test food.
Now, a second study was done looking at betane and soluble fibre. This study had a different base food, more cats, a longer feeding period, and the results are kind of given away here in the title too. It improved body composition and plasma metabolites in cats with CKD.
This study design, there were 6 groups of cats. It's a Willems Latin square design, which just means the food order is rotated, so there isn't a carryover effect. Each food, I fed for, 10 weeks, either a control food or a test food one that contained betane, but half as much o beta glucan and short chain phos as in the previous study, or test food two, which contained the same amounts of betane plus the same amounts of Obeta glucan and and short chain phos.
And monitoring after each test period. The control food was a complete and balanced dry food designed to aid in the management of renal disease, but it had no added betane or fibre from short chain phos or o beta glucan. The test foods were of similar formulation to the control food, except they were supplemented with 0.5% betane and fibre from either short chain phos or obeta glucan.
All the foods contained fibre from brown rice, whole wheat, and barley, with the amount of whole wheat adjusted to accommodate the added betae and short chain foss and op beta glucan. Now, the amounts of crude fibre and total dietary fibre were similar among all foods, but test food one had the highest amount of soluble fibre. The results, oh, well, actually the cats first, their, their mean age was 11.9 or right around 12 years of age.
22 of 24 cats completed the study. These are iris stage 1 CKD cats. Five of them were non-nazotemic but had kidney stones, and one of them had an abnormally small kidney.
The results showed that the intake of fibre did not affect the average daily food intake, and there was no treatment effect following the consumption of each food. No treatment effect on creatinine or BUN following consumption of each food. The total body mass and lean body mass, as we saw before, increased when the cats were fed test food one.
Total body mass tended to be higher, didn't quite make the 0.05 level when the cats were fed test food too, but certainly the trend was there in the right direction. We looked at metabolomics in this study, and plasma metabolomics showed an increase in one carbon metabolism with significant increases in sarcosine and numerical increases in methionine.
Sarcosine is a downstream metabolite of betae. There were lower plasma levels of trans hydroxyprolene and N-methylprolene. These are collagen breakdown products, so perhaps a reduced fibrosis.
Several Aylcarnitines and branch chain fatty acids associated with CKD were reduced when they ate the test food. And there are higher plasma plasma levels of sphingomyelins, and that may reflect a less severe CKD cause some of those have signalling functions. So the conclusion here was consumption of foods with betane and fibres with CKD led to improvements in body composition.
There were a number of changes in the metabolism that corresponded to better kidney health. Betane and the fermentable fibres increased the ability of cats with CKD to utilise food. And the observation that there was improved body composition after consumption of test food one does warrant further research because it had half as much of the fibre levels as the test food too.
OK, that concludes the part on How nutrition affects the GI metabolism. And then the third part, I want to look at phosphorus or the mineral concentration, phosphorus and calcium balance, because we know that phosphorus restriction is at the heart of mineral nutrition to aid in the management of renal disease. And I show that just by looking at two diets here, a renal diet and a maintenance diet.
And the renal diet Has a lower level of protein, primarily to affect the phosphorus percentages. So, 0.5 corresponds to 0.116 grammes per 100 kcals, and 0.9 over here in the maintenance diet responds to 0.180 or corresponds to 10.180 phosphorus.
So, the renal diet is reduced in phosphorus. And the reason that is important and why we talk about phosphate restriction, is because in chronic kidney disease, there's reduced phosphate restriction. So with a decrease in GFR we have a reduced phosphate excretion that leads to chronic phosphate retention or an increase in phosphate.
That has an effect on bone to increase the amount of phosphatonin FGF 23 that's released. And then there's a lot of effects associated with FGF 23. One of them is, that it tries to stimulate phosphate excretion and lower phosphate.
It seems to get limited though, because, in order to do that, it requires the presence of klotho expression, to have its effect at the renal tubular levels, and there's a decrease in alpha klotho with the progression of kidney disease, partly because FGF 23 reduces alpha klotho expression by the parathyroid gland. But some of the other things that FGF 23 does is it inhibits 1 alpha hydroxylase, so we have a reduced amount of the active form of vitamin D, so, a decrease in calcitriol. With the decrease in calcitriol, and the decrease in calcium, and the increase in phosphorus that's going on, those tend to stimulate PTH or parathyroid hormone.
So, we have an increase in parathyroid hormone or renal secondary hyperparathyroidism. If we look at, this is a time scale, and this is in humans, but normal all the way up to stage 5 CKD. This is the normal range, and these are the various parameters.
Phosphate is actually one of the last things to go up out of the normal range. One of the earlier changes is in the uremic toxins. They increase first out of the normal range.
FGF 23 goes up shortly thereafter, and PTH or the parathyroid, hormone, is also kind of delayed like phosphorus. We see a decrease in Clotho levels and a decrease in calcitriol levels. We know that chronic kidney disease is a risk factor for hypercalcemia.
It was shown that about 30% of cats in one study with chronic kidney disease developed hypercalcemia. So, we recently published the effects of two therapeutic renal diets on hormonal and regulatory pathways affecting calcium homeostasis in cats with early-stage chronic kidney disease. There were 20 colony house cats with stage 1 or To CKD in this study, they're 11.5 years old on average.
They were fed one of two diets formulated for renal disease for 140 days. So this is grammes per 100 k cow. Their calcium and phosphorus levels, with a ratio in the moderately phosphate restricted, Food of a 1.2 to 1 in the highly phosphate restrictive food of 2.0 to 1.
There were 18 cats that completed this study. And what we showed overall was that feeding a highly phosphate-restricted food, that's the highly phosphate-restricted food to cats with early stages of CKD is likely to cause an increase in ionised calcium and total calcium. These were significantly different.
An increase in FGF 23. And result in a higher fractional excretion of calcium into the urine. So, here's fractional excretion of calcium into the urine.
This is by day 140. Only one cat had a quantifiable PTH concentration, so it was quite low, probably being reduced by the FGF 23. Only one or two cats had a quantifiable FGF 23 level in the moderately phosphate restricted foods, so we didn't get such a stimulus there to increase the FGF 23 levels.
So, the cats fed the moderately phosphate restricted food, maintained normal ionised calcium and total calcium, with no evidence of hyperphosphatemia, although renal secondary hyperphosphate hyperparathyroidism did persist in in some of the cats. If we looked at the urine, there were increased urine calcium concentrations, remember, in the cats on the high phosphate restricted foods, such that, it resulted in higher calcium oxalate risk index, 30 compared to 563, which predisposes to urine stone formation as calculated by this COI test for calcium oxalate stone risk. We can also see that in the calcium oxalate relative supersaturation being much higher in the cats on the high phosphate restricted diets.
The cats fed the moderately phosphate restricted food had a reduced, at least relatively reduced risk of calcium oxalate stone development. This has also been reported or similar results, with a highly phosphate restricted food, resulting in increased ionised calcium, which are resolved by a lower phosphate restricted food with a lower calcium and phosphorus ratio. This is by Geddis in in 2021.
And in their food, they looked at client-owned cats that had ionised hypercalcemia, greater than 1.4. At diagnosis of CKD they called those a baseline hypercalcemics, or after CKD diagnosis while they were eating a phosphate-restricted diet that had a calcium phosphorus ratio of 1.9.
So you can see that the low protein phosphate restricted diet that they were on was 0.8, calcium phosphate ratio 1.9, and they put them on a moderate phosphate and protein, or moderate protein and phosphate-restricted food of 1.5, bringing that ratio down to 1.3 for calcium to phosphorus.
And what they saw was that after 6 months, the cats that had renal diet-induced hypercalcemia, that's the dotted line, returned to a normal ionised calcium level. The baseline hypercalcemics, however, did not change. So in conclusion with their study, cats that appeared to have ionised hypercalcemia induced by feeding this highly phosphate restricted food with a high calcium phosphorus ratio experienced resolution of their hypercalcemia after transitioning onto a less phosphate restricted diet with a lower calcium to phosphorus ratio.
And in our last study, the effect of dietary calcium phosphorus ratio, this is our most recent study, we're looking at the effects of the ratio on ionised calcium and calcium homeostasis in cats with early-stage CKD. The objective of this study is to evaluate the impact of feeding foods with varying calcium phosphorus ratio on ionised calcium and regulation of calcium homeostasis. We had a moderately, moderate calcium phosphorus ratio and a high calcium phosphorus ratio.
Otherwise, these two foods look pretty much the same. But the thing that's unique about this is that we kept the phosphate levels the same. So, we changed the ratio by increasing the amount of calcium in the, in the food.
So, one ratio, had more calcium, it was a 1.8 to 1 calcium to phosphorus, the one that had less calcium was 1.4 to 1.
These are two foods formulated otherwise for renal disease, fed in a randomised 56 days, so it's a short-term study, crossover study. 11 cats started out either on the moderate or the high calcium phosphorus ratio. They had a washout between, and then went to the opposite food, so it's a crossover study, but only 9 cats completed this study, so it's a relatively small number of cats on this particular study.
Body weight and food intake were consistent across both test foods, so, food intake, however, does go down on a daytime. If you look at day 0 over here to day 56, they're consuming less food, but there's no dietary difference in P values. The azoteial biomarkers increased over time but were similar, so no diet effects, but they are going up.
The creatinine is going up, their SDMAs, so these are progressive CKD cats. If we look at ionised calcium, neither of the diets cause calcium, either ionised or total calcium, to go outside of the normal range after feeding for 56 days. So, 1.36, 1.28.
There is no, effective diet, but it's trend, a small number of cats. I like to consider trends because if there had been larger numbers of animals, maybe we would have seen a difference there. The parathyroid hormone concentration is being suppressed and the cats on the higher ratio of food that goes along with the higher FGF 23 concentration.
It's close to significance, and then phosphate fractional excretion is being reduced. Remember, with progressive kidney disease, that can go down, and that was significant at 0.05.
Calcium concentrations in the urine are tending to go up in the cats on the higher diet at 0.07. The pH is significantly higher in the cats on the higher calcium diphosphorus food.
Total urine protein is also higher on the higher. Ratio of food as the urine protein creatinine ratio is tending to be higher at 0.06, calcium oxalate.
A relative supersaturation, it's not significantly different between diets because both foods have increased across time, but those values are higher than they started out. So, in conclusion, cats consuming this higher calcium phosphorus food versus the moderate calcium to phosphorus ratio of food in early stated progressive CKD, again, it's a small crossover study, 56 days' duration. They both maintained ionised calcium and total calcium within the reference interval, both ratios, 1.4 to 1 and 1.8 to 1.
But cats consuming the higher ratio, 1.8 to 1, had a lower PTH concentration. We know that dietary phosphate restriction is less likely to cause, because they both had the same phosphate level, than increasing ionised calcium concentrations.
That's also been shown by Van den Brock and client-owned cats with azotemic CKD tended to have lower PTH concentrations. There was reduced phosphorus. Reduced vaginal excretion of phosphorus.
Again, the decrease in clothy levels likely explain that with progressive CKD. Higher urine total protein concentrations may reflect a deterioration of glomerular health, and a statistical trend for higher ionised calcium and FGF 23 concentrations. We do need more studies with a broader range of calcium phosphorus ratios to make a definitive conclusion, and also, we need to consider the source of phosphorus, as well.
So, overall key findings and implications, greater proteo activity in the colon produces metabolites that are potential uremic toxins that may affect the progression of renal disease. Food ingredients can be modified to favour sacrolysis in contrast to proteolysis that is associated with a healthier state. Consumption of food with betane and fibres led to improvements in body composition.
We think that's enhanced energy use and changes in the metabolism that correspond to better health. And these changes may aid in offsetting sarcopenia and the chronic inflammation associated with ageing. As far as the mineral, what's recommended, we're gonna suggest the calcium in the range of 0.18 to 0.23, phosphorus 0.1 to 0.16 with a controlled ratio between 1.0 and less than 1.5.
Overall, we showed that protein right around the AFL recommended minimum. It probably is, should be right up there or just a little bit above. The amino, essential amino acids, probably at 150% of the AFCO recommended.
We've shown that long chains PUFA, there's benefits there as well as some antioxidants, betae, and fibre. So I know I'm a little bit long, but I'm happy to answer any questions. Thank you so much, Doctor Hall.
It was a great lecture and I think everyone has learned a little bit more about some of the advances that have, that have happened to kidney disease foods over the years. It's not the same as it was 20 years ago. So much we have learned over time.
So, I have a few messages, a few things just to share prior to the Q&A, but we will get to your questions, in just a second. So please, if there's any more questions, add them into the Q&A box now. But I just wanna thank you, thank everyone for joining us this evening.
We've had great attendance and thank you, Doctor Hall for the lecture. So many of you, may know Hill's portfolio for kidney disease food, but I wanted to share what we have offered because some of these things that Doctor Hall has mentioned during this lecture, things like fish oil, amino acids, betae, are some of the things we have in our food. So I, I really encourage you to give these foods a try in your pets or the patients with chronic kidney disease.
Over the years, we've added a lot of forms and flavours to make sure we can appeal to the patients you are treating. Cats can be, have strong preferences for different forms or types of food. So we wanted to make sure that you have a wide variety of options for your patients.
But while the food is good, one of the biggest things on managing these chronic kidney disease patients is getting a successful transition, getting the start on these foods. And I think that was what Doctor Jean Hall mentioned in the very beginning, was that some of these patients are not on The renal foods that we know support them in their chronic kidney disease. So, here's a, just a few quick tips, making sure you're educating these pet owners.
We know as veterinarians, a lot more about the benefit these, benefits these foods provide. So take the time to educate them. It could be you, a vet nurse in your practise, but make sure they understand the importance.
It's tempting to feed some of these over the counter foods, but if they know how important it is, you're more likely to have compliance. Always start these foods at home when the patient is feeling well. So, we never wanna start it in the hospital, maybe when they're having uremic crisis.
That's how we're gonna develop a quick food aversion. So think about when and how you're gonna offer them. And then All transitions can happen quickly.
Some cats love the new foods, love the stew or the other varieties. I always recommend to owners 3 to 4 weeks or more if needed. Let the cat take its time.
Don't make this a stressful thing. And if you tell owners it could take a while, you're more likely to have success. And if they transition quickly, you are the One who recommended amazing, great tasting food.
So, there's just a few tips to take all of that knowledge Doctor Hall shared and kind of make sure you're getting that nutrition into those patients. Also, Pill's offers a 100% satisfaction guarantee. So, really, you can make it easy for your clients to try these foods.
Now, we had a great CE event tonight. And if you are interested in more CE events, we have a great one coming up offered by Hills. We have our global symposium, which is a two-day event that will be streaming virtually on June 24th and 25th.
It is completely free. We have a QR code to register and I think we're going to have a link in the chat where you can learn more. It's gonna be mostly focused around skin disease, but there's a lot of different topics, both cats and dogs, depending on your preference.
And then, finally, our last message here today because this webinar was put on in collaboration with International Cat Care. So Hill's Pet Nutrition is a proud supporter of the International Cat Care and shares their commitment to improving the lives of cats worldwide. It is a global feline welfare charity focused on advancing cat-friendly care.
It works closely with veterinary professionals, caregivers, and organisations to promote practical, evidence-based approaches to feline medicine, behaviour, and welfare. A key focus is advancing cat-friendly care, helping to raise standards across a wide variety of settings, including clinics, homes, and community environments. Through its educational resources, research initiatives, and international programmes, ICAT Care supports veterinary teams in delivering high quality cat-centered care.
Ultimately, its mission is to ensure that cats experience cat-friendly care in every interaction they have with people in environments where cat. Your care is provided. So, if you want to learn more about this organisation, we have a QR code here.
So just scan that QR code and you can become a member, find clinical resources, guidelines, access to feline-specific CPD courses and materials, and find out more about the cat-friendly clinic accreditation scheme. And their annual World Feline Congress, which is in Wales in 2026. So, tickets are available now to register.
You can also follow them on social media. They have Facebook, Instagram, and LinkedIn. So, thank you very much.
And let me go to our chat or our Q&A to look at which questions we have for Doctor Hall tonight. So We have a question here. In a commercial diet, how can you differentiate a good quality protein from one that is not?
Wow, probably looking at the percent protein is not gonna give you adequate information. I, I, I don't know, but Becky, you can help me out here as well, but short of contacting the company and finding out the percentages of the essential amino acids, I, I think you have to rely on companies that provide those feeding studies, and do the research behind their products to make the claims, just, the number protein. We found there's a lot of things that, can be different.
Yes, I, I completely agree. What's on the bag is just part of the whole picture. There's a lot more that's not, we can't put on bags.
So, definitely talk to the representatives from the company, Call the company to find out more about that product and what it's gonna provide to the patient. OK. Let's go to the next one.
Do you have any thoughts on choice of phosphate blockers? So phosphate binders with kidney disease. I, no, there's a bottom line.
I, I don't have any research to support, choices there. So, you know, short of what you're, you're normally recommending, I, I, I can't add to, to that part. OK.
Let's see, . OK. We have a question about a cat with acute kidney disease.
And then they found out the cat only has one functioning kidney. So I think the question is really about like when you have one functioning kidney, one that's not. After stabilisation, further blood tests show values are OK.
Should we be keeping them on renal diets, when we have one functioning kidney, or do we say, you know, we can go back on a maintenance food because renal values are currently fine? Yeah, as you saw in one of our studies, we did consider a cat with only one kidney to be compromised. Cats have a lot of, reserve kidney function, so even though the biomarkers, the creatinine, BUN, SDMA are all within the normal limits, that cat would still fit within Iris, at least stage one CKD because they do have, a defective kidney.
So, just by Having 2 kidneys, they're down to 50% normal renal function. So we included a cat with only 1 kidney as an iris stage 1 cat in one of our studies. OK.
Thank you so much. And unfortunately, due to time, that will be our last question for tonight. I just want to thank everyone for attending and Doctor Jean Hall for putting this great presentation together and sharing all of your amazing knowledge with the group.
Thank you. I appreciate it.
