Chronic Kidney disease in dogs
Kidneys are bean shaped organs found tucked up high and towards the front of the abdomen in dogs. The right kidney sits a little further forward than the left and can a little challenging to palpate in some dogs. Kidneys have a variety of roles within the body and their function can be a little complex, but in essence they remove waste products from the body, remove drugs from the body, balance the body’s fluids, help regulate the pH of your body and release hormones that regulate both blood pressure and red blood cell production.
If we consider the kidney as a 'waste water processing plant’, this makes it a little easier to understand. Blood from the renal artery (the blood vessel bringing in oxygenated blood to the kidney) can be considered to bring in the ‘waste water’ for the kidney to process. Within the kidney are small kidney units called nephrons, and a small part of the nephron is called the glomerulus. It is here that the ‘waste water' is filtered into the nephron, where it undergoes this ‘processing’. The amount of water that is required to be removed, or alternatively ‘reuptaken’ by the nephrons is determined by the animal’s hydration status. This ‘recycled water’ is returned to the blood stream via the renal vein. This also benefits the body’s blood pressure by maintaining the appropriate hydration status. In addition, the kidneys can impact on circulation via the renin-angiotensin-aldosterone system.
The kidneys also filter out and excrete or retain electrolytes such as sodium and potassium. They also remove and excrete the body’s waste products, including bile, urea. These are removed in the urine after filtration by the kidneys. Another role of the kidneys is hormonal, producing a hormone called erythropoietin that works on the bone marrow to facilitate the production and release of red blood cells. This is why often dogs with chronic kidney disease can have a low grade anaemia.
Finally, kidneys are involved in calcium control through they production of an active form of vitamin D.
Types of Kidney disease
There are two main types of kidney disease. This article’s aim is predominantly to discuss chronic kidney disease, but it is worth mentioning the other type of kidney disease, acute kidney failure, as well.
Acute kidney failure is the acute suppression of kidney function. The insult that causes this acute renal failure equally and suddenly disrupts the function of all the kidney nephrons, without time for the compensatory mechanisms which are involved in chronic kidney disease to kick in. Acute renal failure is potentially reversible, whereas chronic kidney disease is progressive and irreversible. Causes of acute kidney failure can be what we can ‘pre-renal’ (ie a problem with the blood - mainly a lack of it - supplying the kidney), ‘renal’ (ie something damaging the kidney such as infections, drugs, cancer, or acute severe inflammation such as glomerulonephritis), and ‘post renal’ (ie an obstruction to the outflow of urine made by the kidney - for example a stone or cancer blocking the ureter which is the tube leading from kidney to bladder, or a rupture of the bladder, ureter or urethra).
Chronic kidney disease involves the gradual death of nephrons with the remaining nephrons working as normal. The body has amazing ability to compensate for organs not working at 100% of their function because there is ‘reserve capacity’ built into it (hence the reason why many people survive extremely well with just one kidney). However, once a threshold of nephron loss is reached, the ability to completely ‘compensate’ for the reduction in functioning capability of the kidneys is lost, and we start to see changes on blood tests and patients can develop clinical signs. This is what this article is mainly looking at. There is a small window between the percentage of nephrons lost that demonstrate chronic kidney disease is present but compatible with life, and the percentage of nephrons lost that is not compatible with life. Treatment is aimed at preserving these remaining nephrons and supporting those present to work at an optimal level.
Symptoms of chronic kidney disease include increased drinking as the body tries to compensate for the damaged kidney by pushing more bloods (and water) through them. Increased urine is produced because the kidneys cannot ‘reuptake’ what they need to because they aren’t functioning adequately, and the dogs become more thirsty to counter this excessive loss of water. The rise in waste products not being filtered out by the kidneys means that there can be nausea and vomiting with the dogs, a loss of appetite and sometime even mouth of stomach ulcers as the disease progresses. Dehydration occurs in the later stages when dogs cannot keep up with the ongoing loss of water through the urine.
Testing to determine CRD staging
Kidney disease can be diagnosed initially by looking at blood sample results for kidney markers and then looking at these in relation to a urine sample, particularly the concentration of the urine and the protein levels in the urine, as well as to look for any infection which can be common in kidney disease (dilute urine which is found in dogs with chronic kidney disease is a much nicer place to be as a bacteria than strong concentrated urine) . Blood pressure is also checked. Ideally if kidney disease is found, imaging of the kidney and urinary tract would also be performed.
We are now able to stage chronic kidney disease into one of four stages using the IRIS Staging Scheme (IRIS stands for International Renal Interest Society). Initially staging is done by looking at SDMA and/or creatinine levels in the blood. SDMA is a relatively new marker that we look at, and is a measure of the glomerular filtration rate, or GFR. This blood analysis gives the main stage of kidney disease. Stage one is the mildest disease, and stage 4 is the highest.
Substaging takes this further and involves looking at a urine protein:creatinine ratio (which gives us an indication of protein levels in the urine), and also measuring blood pressure. As an example, a dog could be stage 2 kidney disease with borderline proteinuria and hypertensive (high blood pressure). Treatment is then directed at all three areas, tackling any protein loss (which may suggest inflammatory kidney disease), restoring normal blood pressure, and then supporting the kidneys themselves. Staging is dynamic, it gives us a snapshot in time of the stage of disease that the dog is in at the time of testing. This stage will change, usually upwards to a higher stage, and occasionally it can improve and come down.
Staging is a really useful thing to do for a couple of reasons. Firstly it allows us to really make sure that when we start on treatment options we can see if there is rapid progression or if we are ‘holding' the disease. It also allows us to determine certain treatment options that we can use. For example, we often look at phosphate levels when diagnosing and treating kidney disease, and for different stages we want the phosphate level to be in a slightly different range. By monitoring this with knowledge of the IRIS stage of kidney disease, we can decide of phosphate binders are a necessary treatment option or if we have the figure within the range we want purely from diet modification.
A side note on NSAIDs and kidneys
Everyone worries about kidney disease and non-steroidal anti-inflammatory medications (NSAIDs), and that using these drugs can cause kidney disease. Whilst these drugs are not generally licensed for use in dogs with kidney disease, the drugs themselves do not directly damage the kidneys. These NSAID drugs have an effect on prostaglandins, which are a category of compounds found in our bodies that have hormone like effects. One of the roles of prostaglandins is to maintain the blood supply and appropriate blood pressure to the kidneys when there is a drop in systemic blood pressure. This protects the kidneys and their nephrons from oxygen starvation (which would potentially lead to the death of nephrons if it happened). If a dog is taking NSAIDs, this protective mechanism that is orchestrated by the prostaglandins is blocked and so potentially a drop in blood pressure can lead to the kidneys being starved of oxygen and as a result cause the death of nephrons. The question we always have to ask is, what are the chances of a dog having a drop in blood pressure? It is for this reason that the recommendation is to stop any NSAIDs if your dog has vomiting or diarrhoea for example, which may lead to dehydration and a consequent drop in blood pressure.
Treating CRD
Diet - this is the mainstay of treating most kidney disease, and involves feeding a good quality but restricted protein diet, and a low level of phosphorus and sodium/salt. Ideally it increases antioxidants and B vitamins (which are water soluble and often lost through the excessive urination taking place) and increased omega three levels is of significant benefit too. There is some, ongoing discussion about whether the need to heavily restrict protein is as vital in the earlier stages of kidney disease, and if there are not high levels of blood urea (a byproduct of protein breakdown which is removed by the kidneys) then restriction may not need to be as pronounced. However, in the later stages of kidney disease significant protein restriction is definitely necessary, as urea levels rise. In these IRIS stage 3 and 4 cases, protein levels want to be between 14-20% of the dry matter of the food. The difficulty is that often patients in the latter stages of kidney disease have a poor appetite and nausea. If a dog is not eating enough food then muscle wastage can take place, and muscle breakdown and removal by the body is the equivalent of a high protein meal because muscle is protein. Sometimes to increase the palatability and calorie density of a food to avoid this muscle breakdown, increased fat levels of the food can be tried. This may help in getting enough calories into a dog with a poor appetite in order to prevent muscle wastage. However, care must be taken to avoid any gastrointestinal upset from a higher fat diets as a dog who is struggling to manage their hydration due to kidney disease will find it hard to bounce back quickly and well from a bout of gastroenteritis. Picking and balancing a kidney diet to support the dog optimally can be a real challenge and juggling act. If you have a dog with kidney disease then talk to your vets to determine which of food would be best to feed your dog. It is harder to meet the protein restriction requirements, particularly in the latter stages of kidney disease with a raw food diet, and it may be that a bespoke home cooked or raw diet that is clinically formulated specifically for the patient and their needs is required.
Phosphate binders - for some dogs, a change in diet after diagnosis of kidney disease to a restricted protein diet can bring the blood phosphate level back into the range appropriate for the stage of kidney disease present. However, for others, the blood phosphate level will still be too high. In these cases, a vet will often prescribe an oral phosphate binder, and there are several available. Most are calcium based, but sometimes aluminium based binders are used alongside, or instead of the calcium based ones, depending on the dog’s calcium levels and phosphate levels. One phosphate binder available for dogs also has the herb astragalus in it which can be a nice herb for kidney disease - unsurprisingly this one is probably my preferred choice!
Fluid therapy - as discussed beforehand, dogs with chronic kidney disease are prone to becoming dehydrated because their ability to maintain their fluid balance is poor. This further exacerbates the insult to the remaining kidney nephrons, as they potentially suffer more episodes of oxygen starvation. Good hydration is really important. For this reason, intravenous fluids are often used as a form of ‘fluid diuresis’, to rehydrate and help flush out toxic byproducts in the body that would normally be removed by fully functioning kidneys. This can often make dogs feel a lot better, but does requires a (usually short) stay in the vet hospital. Sometimes fluids are given under the skin. The challenge with this is that, particularly for larger dogs - the volumes required to resolve the dehydration when put under the skin are just too much and too uncomfy. Subcutaneous fluids can be used with cats to reasonable effect, and some owners with cats with chronic kidney disease are able to do this daily at home, but it is a treatment option used far less regularly or reliably in dogs.
Drugs - drugs are not used a lot in the treatment of chronic kidney disease, particularly the early stages. Occasionally, for a dog that has a high protein:creatinine ratio in its urine, suggestive of an inflammatory kidney condition such as glomerulonephritis, a type of drug called an ace inhibitor may be used. For dogs with significant anaemia as a consequence of their kidney disease, they may be given injections of the hormone erythropoietin, or EPO. In the latter stages of kidney disease, drugs may be used more to tackle concurrent clinical symptoms such as nausea or stomach ulcerations. In these cases anti sickness medications may be used, or medications that help reduce acid secretions in the stomach and aid the healing of these ulcers.
Herbs - unsurprisingly I love using herbs in cases of chronic kidney disease, as part of an integrative approach to they management. Herbs are great at ‘plugging the holes’ that western medicine can’t. In many of the treatment options above, treatment is aimed at diluting the ‘waste water’ coming into the kidneys (to use the analogy of the kidneys as a waste water processing plant discussed at the start of this article). Fluid therapy, phosphate binders and low protein binders are all helping here. Herbs can be lovely for helping to target the kidney itself, to nourish and support the kidney and assist in its functions. There are loads of herbs that can be useful, but several stand out. Rehmannia, or Chinese foxglove, is particularly impressive. This herb can improve kidney perfusion without causing high blood pressure in the kidneys (whilst low kidney blood pressure is bad, similarly excessively high blood pressure can damage the kidneys in the longterm) by enhancing kidney blood flow whilst opening up the vasculature within the kidney itself. It also works on two stem cell lines in the bone marrow - CFU-S and CFU-E - to promote the release of further red bloods cells, which aids the oxygen carrying capacity of the blood as well as helping to improve any anaemia. Cordyceps, the caterpillar mushroom, has been shown to protect against kidney ischaemia (lack of oxygenation) and reperfusion injuries in rats as well as attenuating kidney tubular damage and fibrosis. Astragalus, or milkvetch, has nice research to back it’s use in the treatment of kidney disease (hence it’s inclusion in one of the phosphate binders available!) - oral doses were shown to improve kidney function in rats with experimental inflammation of the nephrons and it was shown in another experiment to reduce glomerular sclerosis. There are many other herbs that can be beneficial, but as always when it comes to herbs, a full examination by a herbal vet and determination of which herbs are most appropriate for that patient is vital. These vets will also use products that are therapeutic grade and made under good manufacturing practices; this is always important but even more so in patients with kidney disease who will struggle more than most to deal with any adulterants that might be present in products bought from less scrupulous sources.
In conclusion, chronic kidney disease is a relatively common disease process, often occurring in out geriatric patients. The aim of treatment is to support the kidneys and maintain the functioning of the remaining kidney units, the nephrons. This is done mainly through diet, but with additional treatment options. An integrative approach can be really helpful for these patients.