Tuesday, August 30, 2016

SDMA: A New Test Designed to Detect Chronic Kidney Disease Earlier than Before


Chronic kidney disease (CKD) is a common cause of illness in cats, especially older cats.  Previous studies estimated that 1 in 3 cats were likely to develop kidney disease in their lifetime.  A recent study in cats, however, has shown the prevalence of CKD is even higher than formerly believed, with 50% of cats of all ages, and up to 81% of cats aged 15 years and older, having CKD.  The reason for the revision in these numbers is the development of a new test that can detect kidney impairment much earlier than ever before. 

Diagnosing CKD in cats has been relatively straightforward once the disease is in its later stages.  Typically, cats begin showing clinical signs of CKD, for example, increased thirst, increased urination, decreased appetite, weight loss,  and increased nausea or vomiting, as they become elderly.  Upon examination, your veterinarian will likely perform a few standard blood and urine tests, the most informative being a serum biochemistry profile and a urinalysis.  The biochemistry profile may show “azotemia”, an increased level of waste products (primarily creatinine, a breakdown product of muscle) in the bloodstream.  The urinalysis usually reveals a loss of urine concentrating ability.  In other words, the urine is more watery than normal.  This combination of azotemia and poorly concentrated urine confirms that the cat has CKD.

Cats are very good at producing concentrated urine.  As they lose the ability to manufacture concentrated urine, cats will begin to drink more and urinate more.  However, cats, being the unique creatures that they are, seem to maintain their urine concentrating ability pretty far into the disease process, so by the time cats start showing signs of weakening kidneys (excessive thirst and urination, and subsequent watery urine), about 66% of kidney function is compromised.  In many cases, this occurs gradually, and cat owners often fail to notice these initial signs.  If the serum biochemistry panel reveals azotemia, this means that not only does that cat have CKD, but now at least 75% of the kidney’s filtering ability is compromised.  This bears repeating:  by the time we can detect an impairment of the kidney’s filtering ability on our blood tests, there is already a 75% reduction in kidney function.





Unless the underlying cause of the initial kidney injury can be discovered and treated, CKD invariably progresses. In most cases, an underlying cause for the initial renal insult cannot be found.

Sadly, CKD is incurable.  Once the diagnosis is made, the focus is to delay the progression of renal failure, improve the cat’s quality of life, and extend a cat’s survival time through a variety of diet and drug interventions.  If would be ideal if we could recognize cats with early kidney disease before they developed azotemia.  Well, now we can.

The gold standard for measuring kidney function has always been to measure the “glomerular filtration rate” (GFR).  This is an indicator of how effectively the kidneys are filtering the toxins from the blood.  It is cumbersome and impractical to measure GFR routinely in a veterinary practice.  Instead, veterinarians have always used the level of creatinine in the bloodstream to approximate the GFR. However, as mentioned above, creatinine does not increase until 75% of the filtration ability is lost.



 
Symmetric dimethylarginine (SDMA) is a methylated form of the amino acid arginine. It is a breakdown product of protein that is excreted by the kidneys.  The SDMA levels in the bloodstream correlate closely with GFR.  Therefore, as the kidneys start to lose the ability to filter, the SDMA level will rise.  However, the key advantage of the test is that the SDMA levels rise earlier than creatinine.  In fact, a study of 21 cats revealed that SDMA increases, on average, when there is a 40% reduction in filtration ability.  In some cases, SDMA rose with as little as a 25% reduction in filtration.  This translates to being able to detect a decline in kidney function approximately 17 months earlier than a rise in creatinine, allowing for a significantly earlier diagnosis of CKD.   The test is included as part of every chemistry panel run by the Idexx company.  Veterinarians who do not use Idexx as their primary diagnostic laboratory can run the test “a la carte” from Idexx for a small fee. 

What are the implications of being able to diagnose CKD so much earlier than before?   As with all medical conditions, early detection is key to increasing the chances of successful treatment.  As noted above, if an underlying cause for the kidney disease can be discovered, it may be possible to slow or halt the progression of the disorder.  Cats with an elevated SDMA should have a urine culture promptly performed if there is any suspicion at all that a urinary tract infection may be present.  Bacteria in the bladder may ascend up the ureters, resulting in pyelonephritis, an infection of the kidneys.  Discovering this early and addressing the infection may reverse some of the damage to the kidneys and help prevent progression of the CKD. Ultrasound and/or x-rays should be considered, as these tests might reveal the presence of stones in the ureters or the kidneys.  Again, early detection may allow for surgical or medical intervention, improving the prognosis.  Cats with elevated CKD levels should have their blood pressure evaluated, because up to 20% of cats with CKD have high blood pressure. If untreated, high blood pressure can lead to accelerated progression of CKD.  Urine protein levels should also be monitored in cats with elevated SDMA levels.  Cats with significant proteinuria (protein in the urine) tend to fare worse than cats with low or undetectable levels of protein in the urine.  Early recognition and treatment can improve the prognosis for cats with CKD. 

In addition to identifying and treating any underlying causes of CKD, there are other management strategies for cats with CKD that have proven beneficial in slowing the progression of the disorder and improving quality of life.  Dietary therapy is the cornerstone of long-term management of feline CKD.  The benefits of feeding a prescription diet  - one that is restricted in protein, phosphorus, and sodium – have been well documented.  There is still debate on exactly when to start feeding these diets, but most researchers believe that earlier may be better because transitioning to a new food will likely be more successful when the cat’s appetite is still good.  Because the SDMA test allows for an earlier diagnosis of CKD, dietary alterations can be made promptly.  A low potassium level (hypokalemia) is a common finding in cats with CKD.   Hypokalemia contributes to the progression of CKD.  Kidney function improves when low potassium levels are restored using oral supplementation.  Potassium levels should be regularly monitored in cats with CKD, and adjustments made when appropriate.

CKD is an extremely common condition in cats, and the prevalence increases with age.  Incorporating the SDMA test along with a standard serum biochemistry panel may facilitate the early diagnosis of CKD in cats.  Once identified, the swift investigation for an underlying cause may lead to more effective treatment options, slowing the progression of CKD and extending the life of affected cats.


Thursday, August 18, 2016


Disorders of the Feline Spleen


We’ve all heard of the spleen, but do you really know what it does?  And what does a big spleen mean?





Most people can give you a reasonably accurate description if asked to describe the function of the heart, the kidneys, or the lungs. But ask about the spleen and you’re met with blank stares, despite the fact that everyone’s heard of it.  Let’s end the mystery and delve into the world of the feline spleen.

The spleen is a dark red organ located near the stomach.  It is longer than it is wide, and has the appearance of a giant tongue.  It is covered by a capsule made of sturdy fibrous tissue.   Blood vessels enter and exit the spleen on the same side, in an area called the “pedicle”.  The spleen is usually found in the cranial part of the abdomen on the left side, although the exact location isn’t fixed.  Depending on its size and shape, and the size of the surrounding organs (for example, if the stomach is full), the spleen can shift position to the right side of the body, or to the caudal part of the abdomen.

 
The spleen isn’t essential for life. It can be surgically removed if necessary, and most animals will be fine.  However, the spleen performs important functions and it’s certainly much better to have one than to not have one.


The spleen has several important functions.  It plays a role in “hematopoiesis”, the production of red blood cells.  The bone marrow is the major site of red blood cell production. The spleen is the next major site.  The spleen is also a storage site for red blood cells and platelets.  If the body was suddenly in need of additional red blood cells in the circulation, the spleen has the ability to contract, flooding the bloodstream with additional blood.  Another function of the spleen is filtration.  The spleen acts as a giant filter that traps and removes old or abnormal blood cells from the circulation.  A fourth function of the spleen is the trapping and removal of bacteria, foreign proteins, and old cells through a process called phagocytosis, in which cells of the immune system within the spleen engulf the offending particles.  A final important function of the spleen is the participation in the immune response. 

Anatomically, the internal structure of the spleen consists of areas of “red pulp” and areas of “white pulp”, as well as a “marginal zone” which separates the white and red pulp.  The red pulp contains many sinuses that are engorged with blood, giving the spleen its characteristic red color.  It is in the red pulp that the filtration of foreign proteins, microorganisms, and defective or old red blood cells occurs.  The white pulp is where the red blood cells are produced and where the cells of the immune system reside.  The marginal zone is the area that separates the red pulp from the white pulp.  Its primary role is that of blood filtration.

Disorders of the spleen can be generally categorized as either primary or secondary.   In primary spleen disorders, the spleen itself is the site of the illness.   The spleen can also be secondarily affected by a systemic disease occurring elsewhere in the body.   The most common abnormal finding indicating a problem with the spleen is splenomegaly – enlargement of the spleen.  This can usually be detected on physical examination, by carefully feeling the contents of the abdominal cavity during the physical exam. 

Enlargement of the spleen occurs in two forms: localized and generalized.  Localized splenomegaly is a focal enlargement of the spleen, i.e. a splenic mass.  Generalized splenomegaly is a diffuse enlargement of the entire spleen.  Localized splenomegaly is more common in dogs.  Generalized splenomegaly is more common in cats.

Once splenomegaly is detected on physical examination, there are several diagnostic tests that are helpful in evaluating the cause for the enlargement.  A complete blood count, serum chemistry panel, urinalysis and abdominal radiographs may provide useful information.   Abdominal ultrasound is an excellent, non-invasive tool to distinguish whether the enlargement is localized vs. generalized, and to help further define the underlying disease process. 

In many cases, a definitive diagnosis can only be achieved by obtaining a sample of the cells from the spleen.  This can be accomplished either by aspiration or by biopsy.  Fine-needle aspiration is a procedure in which a needle, attached to a syringe, is inserted into the spleen.  A sample from the spleen is then aspirated into the hub of the needle and the contents sprayed onto a microscope slide.  The slides are then sent to a laboratory to be evaluated by a clinical pathologist.  Aspiration can be performed under ultrasound guidance, usually with only mild sedation. This is a safe, reliable method of evaluating patients with splenomegaly. 

If a diagnosis cannot be obtained by the diagnostic tests described above, exploratory surgery of the abdomen may be required to identify the underlying disease process.  Because the entire spleen is likely to be affected in cats, rather than obtain a small piece of the spleen as a biopsy specimen, the entire spleen is removed. The spleen is then submitted to the laboratory for review by a pathologist.  As stated previously, the spleen is an important organ but it is not necessary for survival, and most animals live healthy lives following splenectomy.

In cats, unfortunately, infiltration of the spleen with cancer cells is the most common cause of splenomegaly.  The most common cancer is mast cell tumor or mastocytosis.  Lymphoma and hemangiosarcoma are two other common splenic cancers.  In a study published several years ago evaluating 19 cats who had undergone surgical removal of their enlarged spleen, 10 of the 19 (53%) had mast cell tumor, 4 had hemangiosarcoma (21%) and 2 had lymphoma (11%).   These were the three most common diseases resulting in splenectomy. 


Feline splenic disease is a much rarer entity than its canine counterpart, but it is still an important condition in veterinary medicine.  The prognosis for cats with splenomegaly varies depending on the cause. 

Monday, August 8, 2016

Gastrointestinal Hemorrhage in Cats

Gastrointestinal Hemorrhage in Cats
by Arnold Plotnick, MS, DVM, ACVIM



Gastrointestinal (GI) hemorrhage is defined as the loss of blood into the GI tract.  Loss of blood can originate from various sites in the GI tract – the mouth, esophagus, stomach, small intestine, and large intestine/colon.  When cats bleed from the mouth, esophagus, stomach, or small intestine, the blood gets digested, resulting in melena – black tarry feces.   When cats bleed from the large intestine or colon, it is beyond the point where digestion occurs, and any blood associated with the feces appears red.  Discovery of blood in the feces when cleaning the litter box is one of the more common reasons for cat owners to bring their cat to the veterinarian.


The clinical signs of GI hemorrhage are not limited to the appearance of the feces. Cats with hemorrhage originating in the stomach may vomit up blood.  This is called hematemesis.  If the bleeding is recent, the blood is more easily recognized, as it still looks red in appearance.  If the blood gets partially digested in the stomach before vomiting occurs, the blood takes on the appearance of “coffee grounds”, which may be more difficult for clients to recognize as blood.  Veterinarians and owners should not be misled into thinking that all instances of vomiting blood and black tarry feces indicate hemorrhage of GI origin. Coughing up blood (hemoptysis) is sometimes misidentified as vomiting of blood.  Hemoptysis results from disease of the airways and lungs.  Cats that cough up blood may swallow some of that blood, resulting in hematemesis and melena, delaying or confounding the true diagnosis. Hemorrhage from the nasal cavity – called “epistaxis” – can also result in hematemesis and melena if the amount of blood swallowed is significant.   Ongoing or severe blood loss can result in anemia – a deficiency of red blood cells – that could be life-threatening and may require a transfusion if the cat is to survive.

Making a definitive diagnosis of GI bleeding involves identifying first the site of the hemorrhage, and then the cause.  As mentioned above, the presence of melena localizes the site to the stomach or small intestine.  A history of hemoptysis or epistaxis suggests that the GI tract is just a conduit for the swallowed blood and is not the primary site of the hemorrhage.  Fresh red blood in the feces suggests a large intestine or colonic origin for the bleeding.  Gastrointestinal bleeding may be acute or chronic.  Chronic hemorrhage may be insidious, and thus more difficult to detect. 

If the clinical signs point to upper GI bleeding, the first place to look is the mouth.  Severe periodontal disease, foreign bodies, oral trauma, and bleeding tumors can result in hemorrhage.  The diagnosis and treatment of these disorders is usually straightforward. 

Diseases of the esophagus (the tube connecting the oral cavity to the stomach) are uncommon in cats.  Foreign bodies, tumors, and inflammation of the esophagus secondary to acid reflux are disorders that may lead to esophageal hemorrhage.  Excessive salivation, difficult or painful swallowing, and regurgitation of food are common signs associated with esophageal disease.  Foreign bodies should be removed, either using an endoscope of via surgery.  Tumors of the esophagus may be addressed with surgery or chemotherapy, although the prognosis for these tumors is often grave.  Inflammation resulting from acid reflux is usually treated by administering drugs that suppress gastric acid secretion, as well as drugs that form a protective barrier on the ulcer and foster more rapid healing. 

The stomach is a common site of origin for GI hemorrhage, with gastric ulcers being the most common cause.  In dogs, most cases of gastric ulcer are associated with drug therapy, especially non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids.  Cats rarely get ulcers from corticosteroids, and most NSAIDs are unsafe for cats and thus are rarely given.  In cats, tumors of the stomach are the most common cause of gastric bleeding.  These include gastric carcinomas, lymphoma, and mast cell tumors. Clinical signs again may include hematemesis and melena, chronic vomiting, weakness, lethargy, poor appetite, and weight loss.  Anemia due to the blood loss often leads to the appearance of pale gums on physical examination. Ultrasound of the abdomen is usually helpful in identifying a gastric tumor, however, endoscopy is a better diagnostic test in that it allows direct visualization of the tumor and any associated bleeding, and permits the procurement of biopsy specimens for definitive diagnosis.   Treatment depends on the size, extent, and type of tumor.  Surgical removal may be possible for some tumors.  Others, especially lymphoma, may best be treated with chemotherapy.  A bacterium called Helicobacter has also been associated with gastric ulcers and occasionally gastric bleeding in cats.  Helicobacter is sometimes detected in gastric biopsy specimens during endoscopy.  Because Helicobacter has been identified in biopsy specimens from normal cats, merely finding Helicobacter doesn’t necessarily mean that it is causing illness.  However, identification of the organism in a cat with gastric ulceration and bleeding warrants appropriate treatment.  Treatment recommendations are frequently changing, although they usually consist of giving at least two antibiotics in conjunction with an antacid.

The small intestine is a less common site of hemorrhage than the stomach in cats.  Tumors, as well as severe inflammation from inflammatory bowel disease, are the most likely causes of small intestinal bleeding.  Hookworms are bloodsucking intestinal worms that are more commonly found in dogs, but do occasionally affect cats.  These worms attach to the lining of the small intestine and ingest the cat’s blood.  Severe infections can lead to significant anemia, especially in kittens.  Blood may continue to seep from the site where a worm has bitten, and melena may result.  A diagnosis is made by analyzing a fecal sample.  Most common dewormers will treat hookworm infections. 

Colitis – inflammation of the large intestine or colon – is a very common cause of GI hemorrhage in cats.  There are several potential causes of colitis in cats, such as bacterial or protozoal infections, inflammatory bowel disease, sudden changes in diet, and stress.  Fecal analysis can often detect the presence of intestinal parasites or protozoans.  Inflammatory bowel disease of the colon requires colonoscopy to obtain a definitive diagnosis.  Tumors of the colon are uncommon in cats, but do occur.  If the tumor becomes ulcerated and bleeds, it can be a source of hemorrhage.  Typical signs of colonic disease include straining to defecate, increased frequency of defecation, and urgency to defecate, sometimes resulting in defecation outside the litter box if the cat cannot make it to the litter box in time.  Most cases of colitis result in diarrhea, but not always.  Feces from cats with colitis will often contain excessive mucus, giving it a “slimy” appearance.  Treatment of colitis depends on the inciting cause.  Parasites are treated with dewormers.  Inflammatory bowel disease usually responds to anti-inflammatory medication and feeding a prescription diet.   Tumors of the colon may require surgery and/or chemotherapy.

Not all GI hemorrhage is due to primary GI disease.  Bleeding disorders such as a deficiency in platelets or a disorder of the coagulation system can lead to bleeding tendencies, which may include GI bleeding.  For example, some rodent poisons work by inhibiting certain blood clotting factors, leading to signs of GI hemorrhage. 

Gastrointestinal bleeding is an important cause of anemia in cats and may occur for a variety of reasons.  Some causes are easy to diagnose and treat, such as intestinal parasites, while others, such as tumors, are challenging and may be difficult or impossible to treat.  Cats that vomit blood, pass fresh red blood in the feces, or that have black tarry stools should be evaluated by a veterinarian promptly.

Glossary

Hematemesis – vomiting of blood
Melena – black tarry feces
Hematochezia – passage of fresh blood in the feces
Hemoptysis – coughing up of blood
Epistaxis – hemorrhage from the nasal cavity
Coagulopathy – disorder of the blood clotting system
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