The Ailing Kidney

The Ailing Kidney

 

May 29, 2014

 

From the desk of Dr. Voorheis

 

 

Two weeks ago, I devoted an entire blog to one of the most fascinating and hard working organs in the animal or human body – the kidney.  We talked about what it does and how it functions when all is well with the world.  Now, even though it may have seemed quite detailed, I assure you that we only just touched on the topic. I say “touched on” because the real detail is enough to make my eyes spin so I can only imagine that complete detail would probably make you all hit the delete button rather quickly.  And I certainly don’t want that, so this week I will attempt to provide an interesting peek into the world of the sick kidney without sending anyone into a comatose state.

To cover all aspects of renal disease in tremendous detail is beyond the scope of this blog and really is too much information to absorb in one sitting. Or several sittings for that matter. Rather, it is a better idea to share some basic terms and knowledge in an effort to educate and inform my clients so that you are all armed with the knowledge needed to keep your eyes open and watch for signs and symptoms and be aware of when it may be time to get Fido or Fluffy into the office for a visit.

 As with most diseases, renal disease is most treatable and manageable when it’s caught early.   Statistically speaking, the number one killer of cats is renal disease. Sad, but true. A quick side note: that information (afore mentioned renal disease statistics), known almost intuitively to any small animal clinician, was published in a huge study in Sweden. The numbers were gleaned from Swedish insurance companies and published in 2009 in the Journal of Veterinary Internal Medicine. Nearly 50,000 cats were looked at to determine common causes of death. What I thought was most interesting was that most dogs and cats in Sweden are insured for veterinary care. Remember my insurance blog?  In older dogs, renal disease is a significant player in cause of death, but it is not the most common. Dog statistics are greatly influenced by breed, size of animal etc. The most common cause of death in older dogs is neoplasia (abnormal growth of cells, which may lead to a neoplasm or tumor).

 So, on to the educational part of our session. I’ll start with some terminology that is basic and necessary to understand what we’ll cover this week. First, some terms and then some brief descriptions of the various stages of renal disease. Later, we will talk about signs and symptoms and what to watch for as well as treatment options.

Ÿ  Renal – pertaining to the kidney

Ÿ  Renal disease – implies the existence of renal lesions; it does not qualify the cause, severity or distribution of the lesions or the degree of renal function

Ÿ  Chronic Kidney Disease – refers to a loss of nephrons associated with a prolonged (usually two months or longer) and progressive disease process.

Ÿ  Renal reserve – think of the percentage of extra nephrons available, i.e. those not necessary to maintain normal renal function. Although it probably varies from animal to animal, it is greater than 50% in most dogs and cats.

Ÿ  Renal insufficiency – begins when the renal reserve is lost. Animals with renal insufficiency outwardly appear normal but have a reduced capacity to compensate for stresses such as infection and dehydration and have a reduced capacity to concentrate urine.

Ÿ  Azotemia – is the increased concentration of urea nitrogen (BUN), creatinine and other nonproteinaceous nitrogenous waste products in the blood. There can be non renal causes for azotemia (pre-renal, e.g. dehydration and shock and post renal – lower urinary tract obstruction).

Ÿ  Renal Azotemia – denotes azotemia caused by renal parenchymal issues, i.e. – nephron nonfunction.

Ÿ  Uremia – is the presence of all urine constituents in the blood. It may occur secondary to renal failure or post renal disorders, including urethral obstruction and bladder rupture.

Ÿ  Uremic Syndrome – is the constellation of signs that occurs secondary to uremia. These include oral cavity ulceration, gastroenteritis, acidosis, pneumonitis, osteodystrophy, and encephalopathy).

Ÿ  Renal failure – is a state of decreased renal function that allows persistent abnormalities (azotemia and inability to concentrate urine) to exist; it refers to a level of organ function rather than specific disease entity. Occurs when approximately 3/4 of the nephrons from both kidneys cease to function. That is nephron disease (remember our new friend the nephron from the last blog?) – anything from the glomerulus to the collecting ducts.

Ÿ  Acute renal failure (ARF) – results from an abrupt decline in renal function and is usually caused by an ischemic, toxic or infectious insult to the kidneys. In some instances this can be reversible if we get to the case in time.

Ÿ  Chronic renal failure (CRF) – In contrast, the nephron damage associated with chronic kidney disease (CKD) is usually irreversible, regardless of whether the underlying disease primarily affects the glomeruli, the tubules, the interstitium or the renal vasculature. Irreversible damage to any portion of the nephron renders that nephron nonfunctional. Irreversibly damaged nephrons are replaced by fibrous connective tissue. It is difficult to determine the specific cause once end stage kidney damage is present. CKD occurs over a period of weeks, months, or years and, as stated above is a leading cause of death in both dogs and cats. Once advanced stage CKD has occurred, improving renal function is not possible, but many times it is possible to alleviate the signs. The goal of CKD treatment is 3-fold:

  1.  If possible, identify and correct the primary disease process
  2.  Monitor and slow disease progression
  3.  Alleviate patient clinical signs

So, as you can see there are various stages of renal disease. As I mentioned, catching it early gives your critter the best chance at survival. So, how do we know that renal disease is developing in our dog or cat?  We will go over signs and symptoms in a moment, but first we should talk about the disease itself in a bit more detail.

 Sick kidney 1

The Glomerulopathies

I had thought to basically divide this blog into a discussion on Acute Renal Failure and Chronic Renal Failure. Glomerular disease was going to be included in those topics. I’ve since decided to devote a bit more time to glomerular disease as its own separate topic. Although it is primarily seen as a chronic kidney disease, it deserves mention by itself.  Glomerulonephritis (GN), or inflammation of the glomeruli and tubules, is the most common type of glomerulonephropathy and it is caused by immune complexes within the glomerular capillary walls. It is one of the major causes of chronic kidney disease in dogs. There are other causes of glomerular disease such as amyloidosis (a type of protein – think SharPei dogs, Abyssinian cats) and hereditary glomerular diseases (seen in male Cockers, Samoyeds).

 The disease is characterized by the appearance of proteins in the urine, principally a protein called albumin. The amount of protein in the urine is a direct indicator of the severity of the disease and can be used as a marker of progression as well. Immune complexes present in the glomerular capillary wall are usually responsible for initiating the glomerular damage and subsequent protein loss. Immune what? Immune complexes are circulating antigen (think foreign protein) + antibody (immune response) molecules that may be deposited or trapped in the glomeruli. They can also occur when circulating antibodies react with glomerular antigens (proteins) within the wall of the glomeruli. Finally, sometimes foreign proteins (such as antigens associated with heartworm disease) become trapped in glomeruli capillary wall and attract antibody. Once these guys are trapped in the capillary wall, they attract other inflammatory components and a cascade of events takes place. The result of this dance is a damaged or destroyed glomerulus.  There are a host of conditions associated with glomerulonephritis in dogs and cats and far too many to list here. Some you may be familiar with are Dirofilariasis (heartworm), Pyometra (from my spay/neuter blog), Pancreatitis, Cushing’s disease, and Diabetes in dogs and Feline leukemia virus, Neoplasia, Diabetes and Pancreatitis in cats.

  Sick kidney 2                                         

Signs and Symptoms

There are often no signs associated with low level proteinuria (protein loss through the kidneys). If signs are present, they are often non-specific and mild such as lethargy and weight loss. If protein loss is severe and serum albumin drops to <1.5, we may see edema or ascites (fluid buildup in the abdomen). If the glomerular disease causes more than ¾ loss of the nephrons, then we will see the signs that we typically see with advanced stage CKD (chronic kidney disease). Those signs will be increased thirst, increased urination, poor to no appetite, nausea, vomiting and weight loss. Occasionally, the clinical signs will be associated with one of the underlying infectious, inflammatory, endocrine or neoplastic conditions mentioned above and we will discover the glomerular disease as a faucet of one of those diseases.

 Persistent proteinuria can lead to something called “nephrotic syndrome” which is a constellation of signs. The combination includes proteinuria (excess protein in urine), hypoalbuminemia (low blood albumin), ascites or edema (fluid in abdomen or in tissues), and hypercholesterolemia (high blood cholesterol). In addition, systemic hypertension (high blood pressure) and hypercoagulability are frequent complications in dogs with nephrotic syndrome. Systemic hypertension is common in dogs with GN. Some of these dogs will become blind as hypertension can cause retinal detachment. Most of the time we think the high blood pressure is secondary to kidney disease rather than a primary cause. A word about blood pressure measurement in dogs and cats; it is not as easy and simple as we might think it should be. A consistent and accurate measurement of blood pressure in our small animal patients is frustrating to say the least. Doppler ultrasound can give a systolic measurement but not a mean arterial pressure or diastolic measurement. Breed size of dog or cat and temperament of animal all influence the accuracy of measurement. Oscillometric (indirect) uses an automated system for processing pressure cuff oscillation signals.

 The diagnosis of glomerular disease is made with persistent, severe proteinuria within an otherwise normal urine sediment. The urine protein:creatinine ratio is used to measure the magnitude of protein loss.

 Treatment

Since immune complexes usually cause GN, the primary treatment objectives would include finding and eliminating the cause of the immune complex and reduce the glomerular response to those immune complexes. Elimination of the source of antigenic stimulation is the treatment of choice. An example of this is the proteinuria associated with heartworm disease. Treat the heartworm and the glomerular disease goes away.

Unfortunately, elimination of the antigen source or underlying disease is not always possible, either because we cannot identify the antigen source or we cannot eliminate the antigen source. Immunosuppressive agents, such as cytoxan, imuran or prednisone are not generally recommended in the dog for treatment of GN. Aspirin therapy, ACE inhibitors (benazepril, enalapril), dietary sodium restriction, high quality-low quantity protein diets. Each case is individual and treatment is tailored to that individual. Remember, we do not practice cookie cutter medicine at WBAH. Now, on to the world of ARF.

Acute Renal Failure

As we now know from above, renal failure occurs when approximately 3/4’s of the nephrons of both kidneys cease to function. Acute renal failure results from an abrupt decline in renal function and is usually the result of an ischemic (lack of blood, i.e oxygen supply to tissues) or toxic insult to the kidneys. It is important to remember that the kidneys are highly susceptible to the effects of ischemia and toxicants because of their unique anatomic and physiologic features. The kidneys receive 20% of cardiac output directly which makes them sensitive to blood borne toxicants. Ischemic or toxicant induced injury results in damage to the epithelial cells of the proximal tubules and thick ascending loop of Henle. Huh? Nephrotoxicants interfere with essential tubular function and cause cellular injury, swelling and death. Renal ischemia causes cellular hypoxia, swelling and death. Sometimes tubular lesions from toxic insults and ischemia are reversible if addressed in a timely fashion. Many factors may predispose the kidney to ischemia and toxicant induced injury. Those factors would be the following: 
  • The kidneys receive 20% of cardiac output. The kidney cortex receives 90% of that flow.
  • Glomerular capillaries have a large surface area
  • Proximal tubule and thick ascending loop of Henle cells have high metabolic rate and are susceptible to hypoxia and nutrient deficiency
  • Tubular secretion and resorption may concentrate toxicants within cells
  • Countercurrent multiplier system may concentrate toxicants with the medulla area of kidney
  • Xenobiotic (substance foreign to body) metabolism may generate toxic metabolites. For example, the metabolites of ethylene glycol (radiator fluid) are more toxic than the ethylene glycol is.

 

Acute renal failure

In some cases, ARF inadvertently develops in the hospital setting in conjunction with the performance of diagnostic or therapeutic procedures. Fortunately, these are not common. An example might be the ARF case caused by hypotension (low blood pressure) and decreased renal perfusion associated with anesthesia and surgery. Another example is the use of vasodilators or non-steroidal anti-inflammatory drugs (NSAIDS). Prolonged anesthesia with inadequate fluid therapy in older dogs and cats with preexisting, subclinical renal insufficiency is a cause of renal ischemia and ARF in the hospital setting. The setting where I see the most potential for this kind of injury is during a teeth cleaning. This is where we have the potential for poor communication when discussing cleaning Fluffy’s teeth. It is normal and reasonable for a client to think of their older dog needing his/her teeth cleaned in terms of how that procedure works when they themselves go to the dentist and lay in a chair for an hour while their hygienist cleans their teeth. They get their teeth cleaned; they get up, and walk out and go about their day. This client may also have the feeling that, wow, cleaning my dog or cat’s teeth is expensive; and then the vet wants to do blood work and put the animal on IV fluids? Is this really necessary? The short answer is absolutely! The longer answer is if an animal is placed under an anesthetic, the potential exists for alteration of blood pressure (hypotension – which contributes to poor renal blood flow), for hypothermia (which contributes to poor renal blood flow), and for vasodilation (which contributes to poor renal blood flow). That does not mean you shouldn’t have your dog or cat’s teeth cleaned even at an advanced age. By having the teeth cleaned, you are removing or preventing painful teeth and eliminating one of the sources of immune complex disease that can cause GN.

 In our hospital setting it is recommended that animals undergoing surgery and dental procedures are wrapped in a warm water circulating blanket, assessed for pre-existing renal disease, and receive IV fluid support before, during and after the procedure. This is recommended because of the need to support those nephrons. Most of our clients understand that when these recommendations are made for elective procedures they are made with the pet’s safety in mind. Sometimes, a client will decline IV fluid support without the knowledge of why it was recommended or knowing the added risk that this adds to their pet. This blog attempts to address just one of the reasons for IV fluid support. In addition, even though this is the renal blog, it may be a timely reminder to revisit the insurance blog and the dental blog. If we take a good look at our young dog’s and cat’s mouths (those critters in the 1 to 3 year old age brackets), that’s a good time to not only clean teeth at home, but have those animals brought in for the sedation and hand scale dental prophy. Not only is it way cheaper, it is a way to keep their mouths healthy for life. This young animal dental prophy is only available for those dogs and cats that have grade 1 dental disease.

 As I write this blog, I am grateful to my colleagues, associates and clients at WBAH. We really see very few cases of acute renal failure; much of that is due to the preventative steps my colleagues take when presented with the dog who has a rising red count and diarrhea. I have gratitude to the client who allows us to take the aggressive steps to treat something before it gets so bad that we have to deal with two problems, the initial disease and the secondary acute renal failure.

 The biggest risk factors for acute renal failure in our hospital setting are something I would call “acute on chronic”. Animals with renal insufficiency have a reduced renal concentrating ability. When any hypovolemic event happens, most commonly dehydration caused by vomiting or diarrhea or perhaps a dietary indiscretion, then “bingo” – a critter who was able to handle their renal insufficiency can no longer do so because they are volume depleted.

 There are at home toxins that can lead to acute renal failure and death as well. I covered most of these in the blog entitled “Dangers Lurking in Your Home”. The most common one we see is ethylene glycol toxicity commonly known as anti-freeze toxicity. Just a tiny amount can be fatal to an animal. We see this every year. There is an antidote, but it must be administered quickly or we won’t be successful in preventing fatal renal failure.  Another cause of acute renal failure worth mentioning is the ingestion of pet food containing contaminated wheat and corn gluten and rice protein concentrates. The investigation has focused on melamine and cyanuric acid as the major contaminants; however melamine related substances may also be involved in the toxicity. It is thought that a chemical reaction between melamine and cyanuric acid produces insoluble crystals that form in the distal tubules of affected animals, compromising renal function. There is a pet food recall resource at http://www.petpoisonhelpline.com/category/product-recalls/feed/ . Fortunately, this problem is on the marked decline. There are medications that will cause renal issues as well. Generally speaking, certain antibiotics are avoided in known dehydrated animals. For the arthritic dog who develops vomiting and diarrhea we will avoid giving his non steroidal anti-inflammatory medications until he is properly hydrated again.

 Treatment

In general the treatment of ARF is to establish renal perfusion and correct dehydration. In the ARF animal, hydration needs are corrected quickly (rehydrate within 6 hours) as opposed to rehydrating over 24 hours. Treatment priorities are fluids, phosphate binders, anti-emetics, acid blockers and sometimes judicious use of diuretics and ACE inhibitors. Electrolyte monitoring is also key. In some cases animals are referred for peritoneal dialysis or hemodialaysis.

 Chronic Kidney Disease

 The cause of CKD is usually difficult to determine because by the time an animal has CKD the endpoint of irreversible glomerular and tubular damage is the same. Nevertheless, recent studies have shown that primary glomerular disorders are a major cause of CKD in the dog. Because glomerular filtration is uniformly reduced, CKD may be considered a single pathologic entity, although diverse pathways can lead to this end point.  Below is a tablet that highlights potential causes of chronic kidney disease in dogs and cats.

  • Potential Causes of Chronic Kidney Disease in Dogs and Cats
  • Immunologic Disorders – Systemic Lupus Erythematosus, Glomerulonephritis, Vasculitis (e.g. Feline Infectious Peritonitis)
  • Amyloidosis
  • Neoplasia
  • Nephrotoxicants
  • Renal Ischemia
  • Inflammatory or Infectious Causes – Pyelonephritis, Leptospirosis, Renal Calculi
 

  • Hereditary and Congenital Disorders – Renal hypoplasia or dysplasia, polycystic kidneys, Familial Nephropathies (Lhasa Apsos, Shih Tzus, Norwegian Elkhounds, Rottweilers, Bernese Mountain Dogs, Chow Chows, Newfoundlands, Bull Terriers, Pembroke Welsh Corgis, Chinese Shar-Peis, Doberman Pinschers, Samoyeds, Golden Retrievers, Standard Poodles, Soft Coated Wheaten Terriers, Cocker Spaniels, Beagles, keeshonds, Bedlington Terriers, Cairn Terriers, Basenjis, Abyssinian cats
  • Urinary Outflow Obstruction
  • Idiopathic

 At the level of the kidney, the fundamental pathologic change that occurs is a loss of nephrons and a decreased GFR. Reduce the GFR and that results in an increase in plasma concentrations of substances normally eliminated by the kidney. Uremic syndrome is the constellation of signs thought to occur as a result of these substances accumulating.  These signs affect sodium and water balance, red blood cell count (anemia), carbohydrate intolerance, neurologic disturbances, gastrointestinal tract disturbances, osteodystrophy, immunologic incompetence and acid base disturbances. As I have mentioned before, the kidneys also function as endocrine organs. When they fail, hormonal disturbances will occur.

 Kidney Vs Kidney                                     

Signs and symptoms

CKD develops over a period of months to years and the signs are often mild at first. These signs include a history of weight loss, polydipsia-polyuria, poor body condition, non-regenerative anemia and small and irregularly shaped kidneys. The diagnosis is made based on compatible history, physical examination and laboratory findings. Radiographs and ultrasound can be performed to identify or rule out potentially treatable causes of CKD, such as pyelonephritis and renal urolithiasis (stones). The International Renal Interest Society has come up with a staging system to help better diagnose, understand and treat feline and canine kidney disease.

 Serum creatinine concentrations must always be interpreted in light of the patient’s urine specific gravity and physical examination findings to rule out prerenal and postrenal causes of azotemia. The CKD stages are further classified by the presence of absence of proteinuria and systemic hypertension.

Treatment

 In general, characterization of the renal disease and its stability is most important in early stages of CKD when appropriate treatment has the greatest potential to improve or stabilize renal function. In the later stages of CKD, most therapeutic efforts are directed at treating the problems such as inappetence, vomiting, acidosis, potassium depletion, hypertension, anemia and other signs that come up.

 For example, many of these cats and dogs may have dietary changes to reduce their serum phosphorus, and ACE inhibitors to normalize systemic and intraglomerular pressures. Very often, especially with cats, we will have owners administer fluids subcutaneously several times a week. Potassium supplementation is often used and both dogs and cats with CKD are often potassium depleted. Bacterial UTI’s are tested for and treated. Phosphate binding agents are fed to try to reduce serum phosphorus and control secondary renal hyperparathyroidism. Non-regenerative anemias can be managed by use of injectable erythropoietin (EPO). We are fairly conservative with the use of EPO in dogs and cats as the only available EPO is a human variety and over time dogs and cats build up antibodies to it.

 So, that is the ailing kidney in a nutshell. I really did try to simplify it as much as possible. I realize it was a bit heavy this week so I think it’s terrific that you read this all the way to the end. Thank you! As always, keep a watchful eye on your critters and bring them in if you notice anything abnormal. Early detection is key to helping our furry friends.  

 Until next time,

 Dr. Voorheis

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