Diabetes Insipidus

Liaison: Marie Monaco

Diabetes insipidus is an endocrine disease characterized by the inability of the kidney to concentrate urine. This results from a failure to reabsorb water from the glomerular filtrate back into circulation. Symptoms include polyuria (excessive urination) and polydipsia (excessive thirst).

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Diabetes insipidus has been described in dogs as early as 1951 [1]. Diabetes insipidus is a disease of the endocrine system characterized by a deficiency in antidiuretic hormone (ADH) activity. This hormone, also referred to as vasopressin or arginine vasopressin (AVP), is synthesized by neurons in the hypothalamus and stored in the posterior pituitary gland. Antidiuretic hormone acts on the kidney to promote concentration of urine by removing water from the glomerular filtrate back into circulation. This is accomplished through the binding of the hormone to the tubular cells of the kidney, resulting in the insertion of a specific protein (aquaporin 2) into the cell membrane. This protein then functions as a water channel, permitting concentration of urine and conservation of bodily water. Antidiuretic hormone is secreted in response to changes plasma osmolality and blood volume. A deficiency of ADH activity can result from either

a deficiency of ADH (called central diabetes insipidus (CDI)), or
an inability of the kidney to respond to ADH (called nephrogenic diabetes insipidus (NDI))

Dogs have been reported to have both forms [2, 3].

Signs and Symptoms

Dogs with DI present with polyuria (excessive urination) and polydipsia (excessive thirst). The polydipsia is secondary to the polyuria; that is, the need to drink large quantities of water is caused by the loss of water in urine. Generally speaking, polyuria is defined as urine production greater than 50ml/kg/day and polydipsia as water consumption greater than 100ml/kg/day. If the water lost in the urine is not replaced through increased consumption, dehydration can result. Severe dehydration can lead to coma and death.

Causes

The causes of DI can be congenital, involving either failure to produce ADH (CDI) or failure to produce the correct machinery for responding to ADH (NDI). Thus the genetic mutation can reside in the gene that codes for ADH (CDI) or the genes that code for the ADH receptor or aquaporin 2 (NDI) [4]. Diabetes insipidus can also be acquired as a result of an insult (trauma, tumor, surgery, infection or other disease) to either the hypothalamic-pituitary axis (CDI) or the kidney (NDI) [5-7]. An excellent summary of the differences between the two forms of DI can be accessed at:

http://www.mirage-samoyeds.com/diabetes2.htm 2 bones

Risk Factors

In general, DI can affect dogs of any age, sex or breed. The exception is congenital DI, which is X-linked and therefore predominantly seen in males [4].

Diagnostic Tests

The combination of polyuria/polydipsia can be an indication of a number of disease states, and much has been written on making a differential diagnosis when presented with this scenario [8, 9]. Once other potential diagnoses, such as diabetes mellitus, Cushing’s disease, chronic renal failure or pyometra have been ruled out, then tests for DI can be undertaken. The first indication of DI in a dog with polyuria/polydipsia is a low urinary specific gravity in the face of otherwise normal blood and urine chemistries. In other words, the urine is very dilute, having little color or odor. Such findings are consistent with either DI or psychogenic water consumption (polydipsia thought to be caused by psychological factors and not secondary to polyuria). To differentiate between the two, a modified water deprivation test is carried out. By depriving the dog of water overnight, one can test for the ability to make and/or respond to ADH. A normal dog or a dog with psychogenic-mediated water consumption will produce concentrated urine under these circumstances; a dog with DI will not. Failure to produce concentrated urine following water deprivation is indicative of DI. This is usually followed by administration of a synthetic ADH analog called desmopressin (dDAVP), which is available either as a nasal spray (used as eye drops when given to dogs) or a more convenient pill form. If the dog is able to concentrate urine following administration of dDAVP, then the DI is central. If the dog fails to concentrate, then NDI is suspected. These tests cannot differentiate between congenital and acquired DI.

Treatment Guidelines

Note: Treatment of animals should only be performed by a licensed veterinarian. Veterinarians should consult the current literature and current pharmacological formularies before initiating any treatment protocol.

Diabetes insipidus is not a life-threatening disease provided the dog has free access to water. The excessive loss of water in urine as the result of decreased ADH activity can easily be compensated for by an increase in water intake. However, DI can be a problem for dogs that need to rely on the owners for bathroom breaks. A dog with DI will have to be walked more frequently than a normal dog. In cases of CDI, the condition can easily be treated with daily administration of dDAVP; however, this medication is on the expensive side. In addition, attention must be paid to dogs that are incapacitated and may not be able to drink freely. For example, if a dog with DI is about to undergo a surgical procedure, the hospital staff should be apprised of the dog’s diagnosis of DI to make sure that they are aware of and attend to his water needs. Nephrogenic DI, by definition, is unresponsive to ADH; however in some cases, such as those involving a decrease in receptor affinity, increasing the dose of dDAVP can compensate for the defect [4]. In other cases, oral thiazide diuretics can, paradoxically, be used to promote urine concentration. Non-steroidal anti-inflammatory drugs may also be effective.

References

[1] S. Pollock, Diabetes insipidus in the dog, J Am Vet Med Assoc 117 (1951) 12-15. (unable to rate)

[2] E.B. Breitschwerdt, J.W. Verlander, T.N. Hribernik, Nephrogenic diabetes insipidus in three dogs, J Am Vet Med Assoc 179 (1981) 235-238. (unable to rate)

[3] M.F. Harb, R.W. Nelson, E.C. Feldman, J.C. Scott-Moncrieff, S.M. Griffey, Central diabetes insipidus in dogs: 20 cases (1986-1995), J Am Vet Med Assoc 209 (1996) 1884-1888. 3 bones

[4] H. Luzius, D.A. Jans, E.G. Grunbaum, A. Moritz, W. Rascher, F. Fahrenholz, A low affinity vasopressin V2-receptor in inherited nephrogenic diabetes insipidus, J Recept Res 12 (1992) 351-368. 2 bones

[5] M.M. Goossens, A. Rijnberk, J.A. Mol, J. Wolfswinkel, G. Voorhout, Central diabetes insipidus in a dog with a pro-opiomelanocortin-producing pituitary tumor not causing hyperadrenocorticism, J Vet Intern Med 9 (1995) 361-365. 3 bones

[6] J.M. Authement, R.J. Boudrieau, P.M. Kaplan, Transient, traumatically induced, central diabetes insipidus in a dog, J Am Vet Med Assoc 194 (1989) 683-685. 3 bones

[7] D.J. Davenport, D.J. Chew, G.C. Johnson, Diabetes insipidus associated with metastatic pancreatic carcinoma in a dog, J Am Vet Med Assoc 189 (1986) 204-205. 3 bones

[8] R. Nichols, Polyuria and polydipsia. Problems associated with patient evaluation, Probl Vet Med 2 (1990) 610-616. 2 bones

[9] E.C. Feldman, R.W. Nelson, Diagnostic approach to polydipsia and polyuria, Vet Clin North Am Small Anim Pract 19 (1989) 327-341. 2 bones

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