By 

Susan Thorpe-Vargas, Ph.D.

The behavior we are referring to is the need for frequent urination. Seldom do owners and veterinarians search for potential medical problems that might contribute to house soiling behaviors. And, if they do, seldom are those searches for medical causes of inappropriate elimination practices complete. At least a quarter of all dogs euthanized or turned into shelters are given up because of behavior related issues. Near the top of the list of reasons for euthanasia and being turned into shelters is house soiling. Therefore, whenever an inappropriate elimination behavior develops, look first for an underlying medical condition before starting training or behavior modification exercises.

While diabetes insipidus (DI) is less common than its better-known form, diabetes mellitus, it is probably an under-reported disease as it shares symptoms with other more common diseases including diabetes mellitus. The disease can also go unnoticed if the dog has a constant supply of water and has access to an outdoor run or a doggy door so that his excessive elimination needs do not require human intervention. Nonetheless, the disease is dangerous, and severe dehydration can occur very rapidly (4-6 hours). Leaving a DI dog unattended without water for several hours or overnight may result in severe hyperosmolality, coma, and death.

Dr. Marie Monaco whose female Samoyed struggled with the problem, going in again and again to the vet until the problem was recognized, says "We would never have known there was a problem if India had had access to a yard." India was fortunate enough to be seen by a vet familiar enough with the problem to be able to eventually make the proper diagnosis. Dr. Gail Zausner has seen several other patients with this disease since she first diagnosed Marie's Samoyed. "I caution all dog owners to be on the look out for changes in drinking and urination patterns" Water consumption exceeding 100 ml/kg or urine production exceeding 50 ml/kg body weight per day is common to both types of DI. These rates should be viewed as guidelines as environment, activity levels, etc., may cause significant variance.

Diabetes Insipidus, which we refer to as "the other diabetes, is characterized by extreme thirst and frequent copious urination. DI exists to two forms, Central Diabetes Insipidus (CDI) and Nephrogenic Diabetes Insipidus (NDI). Figure 1 summarizes the differences between the two diseases. CDI and partial CDI can be either congenital (existing since birth) or acquired later in life. Dogs of any age, sex and breed are at risk for CDI. On the other hand, NDI is a rare genetic disorder, usually diagnosed in younger animals.

Figure 1. Comparison of CDI and NDI

Kidney Function

To understand DI, in any of its forms, requires first a general understanding of how the kidneys function, and how various hormones regulate that function.

The kidneys are a pair of bean-shaped urinary organs that lie below the lumbar region of the vertebrae on either side of the spinal column. The major role of the kidneys is to maintain fluid and electrolyte balance and to rid the body of toxic metabolic waste products. To do this, the kidneys filter blood and produce urine. Three basic processes are involved in the formation of urine: glomerular filtration, tubular reabsorption and tubular secretion. The smallest functional unit capable of producing urine is called a nephron. These tiny filtration units filter the blood under high pressure, removing urea, salts and other soluble wastes. The filtered and purified fluid is then returned to the blood in amounts necessary to maintain the water balance of the body. The wastes are accumulated and excreted as urine. To explain these rather complicated processes, let us follow the course of a molecule of water as it enters the kidney from the bloodstream. As necessary, please refer to Figure 2.

Figure 2. Flow Diagram of Forming and Expelling Urine

• The water molecule carried in the blood enters one of the kidneys from the aorta by way of either the left or right renal artery. 
• The renal arteries branch out into smaller and smaller arteries and finally to the smallest arteries called afferent arterioles. It may help to think of the branching process as a major limb on a tree branching into smaller and smaller branches. 
• The kidney controls filtration pressure by secreting renin, which in turn leads to the formation of angiotensin II which causes the arterioles to contract, thus raising the blood pressure. 
• Each afferent arteriole in the cortex of the kidney branches into a ball-like mass of very tiny, coiled and intertwined capillaries called a glomerulus. Given the number of afferent arterioles, there are thousands of glomeruli in the cortex region of each kidney. 
• As blood passes through the glomeruli, the filtration, reabsorption and secretion processes begin. 

Hormones control the function of the kidneys in regulating the water content of the body. The hypothalamus, a small but very important gland located in the middle of the brain, manufactures the antidiuretic hormone, ADH (also known as arginine vasopressin) for subsequent storage in the pituitary gland that is attached to the hypothalmus by a thin stalk. ADH is released when the blood volume falls, when a large amount of salt shows up in blood, or when pain or stress are present. ADH release by the pituitary gland stimulates reabsorption of water into the blood. If water intake is not enough to make up for the water lost in perspiration and in breathing, the pituitary gland releases more ADH, thus reducing the amount of water released in urine. If the blood is too dilute, the pituitary gland reduces the secretion of ADH, causing a larger flow of water into urine. . This negative-feedback control is stimulated by a water deficit. Too little ADH released results in an over-excretion of dilute urine, dehydration and death. Vasopressin reaches the membrane of the tubular cells lining the distal and collecting tubules by way of the circulatory system, whereupon it binds with specific receptor sites. This binding activates a process called the cyclic AMP second messenger system that in turn initiates the insertion of the water channels into the cell membrane. Many hormones do not actually enter their target cells. Instead, these "first messengers" issue their commands by the binding of receptors on the surface of the cell membrane and initiate a "PPsst, pass it on" process.

Two Types of Diabetes Insipidus

Both forms of DI share a lack of, or inability to use the hormone arginine vasopressin with the subsequent result that water is not retained by the body. 

In summary:

Central diabetes insipidus (CDI), also known as "vasopressin-sensitive DI," is a disorder of water balance where there is a lack of or an inadequate amount of antidiuretic hormone (ADH). Therefore the dog is unable to concentrate urine. The underlying cause may be a congenital defect, trauma or a tumor on the hypothalamus where ADH is manufactured or damage to the pituitary where it is subsequently stored for future release. Recent research has shown that a possible genetic cause of CDI maybe a mutation in the protein responsible for the proper cleavage of the initial form of the vasopressin hormone.

Signs and Tests: 

• polyuria (excessive urination)
• polydipsia (excessive drinking)
• electrolyte imbalance
• possible dehydration
• low ADH levels
• urinalysis shows a low specific gravity.

Diagnosis: 

1. ruling out other causes, to include Cushing's disease, diabetes mellitus, renal failure, liver disease, and pyometra in bitches; 
2. imagery of the pituitary with a positive finding of a tumor; 
3. water deprivation test--if animal is unable to produce more concentrated urine as water intake is restricted; 
4. ADH trial with desmopressin (the drug used to treat DI)-a positive response to the drug indicates the dog has DI

Treatment: Intranasal, oral tablet, eyedrop or subcutaneous injection administration of desmopressin.

Prognosis: Variable, but not life threatening if treated and adequate fluid intake is maintained.

Nephrogenic diabetes insipidus (NDI), also known as "vasopressin-resistant DI," is a disorder of water balance where the pituitary produces adequate ADH, but for some reason, the kidneys do not respond to it. There are in essence two kinds of NDI: 1) where damage or mutation has occurred and the activity of the receptor site in the kidney is disrupted; and 2) where the aquaporins fail for some reason to fail to adequately support the passive return of water to the blood. In either case, the kidney fails to respond to adequate levels of ADH.

Signs: Same as for CDI.

Diagnosis: Same as for CDI, except that if urine does not become more concentrated after ADH testing, this indicates failure of the kidney to utilize ADH.

Treatment: Oral chlorothiazide (a thiazide diuretic) to help the kidneys concentrate urine. Thiazides paradoxically reduce urine output in patients with diabetes insipidus (DI). Chloropropamide to increase the effects of ADH on the kidney receptor sites. Nonsteroidal anti-inflammatory drugs (NSAIDs) may sometimes be used to good effect. Lowered salt intake.

Prognosis: Congenital NDI is a chronic condition requiring life-long treatment. Advances in molecular genetics have identified over 70 mutations (x-linked) involving the vasopressin receptor sites including binding, defects in their synthesis, processing or intracellular transport or function. Another thirteen mutations have been found to inactivate the vasopressin-regulated water channel aquaporin-2 (a recessive autosomal mode of inheritance). Current work focuses on using gene therapy to insert the normal gene sequences to restore function, but that is still far in the future. Acquired NDI may resolve of its own accord, or may be a long-term condition.

Living with the DI Dog

Unless the diabetes insipidus was acquired, and the problem resolved spontaneously or with treatment, keeping a dog with the condition involves making a number of life-style changes. The first and most immediate change will be to see that the dog has a continuous supply of drinking water. The second change will be to see that the dog has a nearby place to urinate. Even with medication, the urge can come on very suddenly, and in most cases, the dog will not be able to go more than an hour or so without urinating. If you do bring a dog in, the housekeeping aspects may be ameliorated somewhat with a "dog door" leading outside. But, be prepared for accidents. The veterinary side lacks the support groups of the human side where there is a Diabetes Insipidus Foundation and a Diabetes Insipidus and Related Disorders (DIARD) Network. . These are good sources of information concerning how to live with a child or family member with DI, and thus contain useful information for owners with DI dogs. The DI Foundation's quarterly newsletter, "Endless Water" sums up the problem.

Easily cleaned linoleum and urine catching dog beds such as the SleepPee-Time Beds™ are useful for small dogs and for medium to large dogs in mild DI cases. (Editor's note: the SleepPee-Time Beds ™was previously mentioned in the October '99 issue) A large DI dog can produce 2 gallons of urine per day. That amount of urine requires special accommodation if the dog is to be kept in other than a yard or a kennel. The Puppy Go Potty™ may be the answer to this problem. If accidents do happen the stain and odor remover Get Serious!® has been shown to be very effective. (Editor's note: Puppy Go Potty™ and Get Serious!® were previously reviewed in the December '99 issue of Dog World) ,

We wish to leave you with the thought that without sufficient ADH to produce normal urine output, or failure of vasopressin receptors to respond to the ADH levels, or failure of the aquaporins to return fluid back to the blood, there is nothing that the dog can do to reduce its urine output. When it has to go, it has to go. That is all there is to it. This is not a behavioral problem. When travelling with a DI dog, make frequent stops for urination and drinking. It is very easy to dehydrate a DI dog, especially on a hot day with potentially fatal results.

Note--This article first appeared in Dog World magazine.