Polyuria, Polydipsia and Diabetes Insipidus
Richard W. Nelson, DVM, Diplomate ACVIM
School of Veterinary Medicine, University of California
Davis, CA, USA
Water consumption and urine production are controlled by complex interactions among plasma osmolality and volume, the thirst center, the kidney, the pituitary gland, and the hypothalamus. Dysfunction in any of these areas results in the clinical signs of polyuria (PU) and polydipsia (PD). A variety of metabolic disturbances can cause PU/PD (Table 1). Perhaps the least common but most interesting is diabetes insipidus (DI).
Central diabetes insipidus (CDI) is a polyuric syndrome that results from a lack of sufficient arginine vasopressin (AVP) to concentrate the urine for water conservation. This deficiency may be absolute or partial. An absolute deficiency of AVP causes persistent hyposthenuria (urine specific gravities # 1.006) and severe diuresis, even with severe dehydration. A partial deficiency of AVP also causes persistent hyposthenuria and a marked diuresis during periods of unlimited access to water. During periods of water restriction, dogs and cats with partial CDI can increase their urine specific gravity into the isosthenuric range (1.008 to 1.015) but cannot concentrate urine above 1.020, even with severe dehydration. Maximum urine concentrating ability with partial CDI is inversely related to the severity of the deficiency in AVP secretion.
CDI may result from any condition that damages the neurohypophyseal system. Idiopathic CDI is the most common form, appearing at any age, in any breed, and affecting animals of either sex. The most common identifiable causes of CDI in dogs and cats are head trauma, neoplasia, and hypothalamic-pituitary malformations. Primary intracranial tumors causing DI in dogs and cats include craniopharyngioma, pituitary chromophobe adenoma, and pituitary chromophobe adenocarcinoma and metastatic tumors include metastatic mammary carcinoma, lymphoma, malignant melanoma, and pancreatic carcinoma.
Nephrogenic diabetes insipidus (NDI) is a polyuric disorder that results from impaired responsiveness of the nephron to the actions of AVP. Plasma AVP concentrations are normal or increased in animals with this disorder. NDI is classified as primary (familial) or secondary (acquired). Primary or familial NDI is a rare congenital disorder in dogs and cats that results from a congenital defect involving the cellular mechanisms responsible for insertion of aquaporin-2 water channels into the luminal cell membrane. PU and PD typically become apparent by the time the dog or cat is 8 to 12 weeks of age.
Acquired secondary NDI includes a variety of renal and metabolic disorders which interfere with the normal interaction between AVP and its renal tubular receptors, affect renal tubular cell function, or decrease the hypertonic renal medullary interstitium, resulting in a loss of the normal osmotic gradient (Table 1). These disorders resemble primary NDI but AVP, AVP receptor sites, and postreceptor mechanisms responsible for water absorption are present.
In dogs and cats, normal water intake varies from 20 to 70 ml/kg per day and normal urine output varies between 20 and 45 ml/kg per day. PD and PU in the dog and cat have been defined as water consumption greater than 100 ml/kg/day and urine production greater than 50 ml/kg/day, respectively. If 24-hour water intake is increased, a diagnostic evaluation for the cause is warranted. However, if 24-hour water intake is normal, pathologic PU and PD are unlikely and another inciting factor (e.g., hot weather) should be sought or misinterpretation of polyuria (e.g., dysuria instead of polyuria) should be considered. If the owner is certain that a change in the volume of water consumption or urination exists, even though water consumption is still in the normal range, a diagnostic evaluation may still be warranted.
Assessment of urine specific gravity may be helpful in identifying PU and PD and may provide clues to the underlying diagnosis, especially if multiple urine specific gravities are evaluated. Urine specific gravity varies widely among healthy dogs and, in some dogs, can range from 1.006 to greater than 1.040 within a 24 hour period. Wide fluctuations in urine specific gravity have not been reported in healthy cats. Urine specific gravities measured from multiple urine samples that are consistently less than 1.030 (especially less than 1.020) support the presence of PU and PD and the need for a diagnostic evaluation to determine the cause. Identification of one or more urine specific gravities greater than 1.030 supports normal urine concentrating ability and an intact, functioning pituitary vasopressin-renal tubular cell axis. Dogs and cats may still have PU and PD despite identification of concentrated urine; possible differentials include disorders causing an osmotic diuresis (e.g., diabetes mellitus), psychogenic polydipsia and disorders in the regulation of AVP secretion.
The initial diagnostic tests for PU and PD include a CBC, serum biochemistry panel, urinalysis with bacterial culture, and a serum thyroxine concentration in older cats. Depending on the history and physical examination findings, abdominal ultrasonography may be warranted to evaluate the liver, kidneys, adrenal glands and uterus. Careful evaluation of the history, physical examination findings, and initial database usually provides the diagnosis outright or offers clues that allow the clinician to focus on the underlying cause. Occasionally, the physical examination and initial database appear normal in the dog or cat with PU and PD. Viable possibilities in these dogs and cats include DI, psychogenic water consumption, unusual hyperadrenocorticism, renal insufficiency without azotemia, and possibly mild hepatic insufficiency. If the urine specific gravity measured on multiple urine samples is consistently in the isosthenuric range (1.008 to 1.015), renal insufficiency should be considered the primary differential diagnosis, especially if the BUN and serum creatinine concentration are high normal or increased (i.e., $25 mg/dl and $1.8 mg/dl, respectively) and proteinuria is present. Although isosthenuria is relatively common in dogs with hyperadrenocorticism, psychogenic water consumption, hepatic insufficiency, pyelonephritis, and partial CDI with concurrent water restriction, urine specific gravities tend to fluctuate above (hyperadrenocorticism, psychogenic water consumption, hepatic insufficiency, pyelonephritis) and below (hyperadrenocorticism, psychogenic water consumption, partial CDI) the isosthenuric range in these disorders. If the urine specific gravity is consistently less than 1.006, renal insufficiency and pyelonephritis are ruled out and DI, psychogenic water consumption, and hyperadrenocorticism should be considered. Diagnostic tests to assess for hyperadrenocorticism (e.g., ACTH stimulation test), liver function (e.g., pre and postprandial bile acids), and renal insufficiency (urine p/c ratio, diagnostic imaging) should be considered before tests for DI.
The diagnosis of DI and psychogenic water consumption is based on results of the modified water deprivation test and response to synthetic vasopressin (dDAVP) therapy. All realistic causes of secondary acquired NDI should be ruled out before performing tests to diagnose DI and psychogenic polydipsia. The modified water deprivation test is designed to determine whether endogenous AVP is released in response to dehydration and whether the kidneys respond to this stimulus. When the test is properly completed, one can differentiate CDI from NDI from psychogenic polydipsia. The modified water deprivation test serves no other purpose and is not meant to be a test of renal function.
An alternative approach is to evaluate the animal's response to trial therapy with dDAVP (Desmopressin Acetate). One-half to one 0.1 mg or 0.2 mg dDAVP tablet is administered orally every 8 hours or 1 to 4 drops of dDAVP nasal spray is administered from an eye dropper into the conjunctival sac every 12 hours for 5 to 7 days. Owners should notice a decrease in PU and PD by the end of the treatment period if the PU and PD are caused by CDI. An increase in urine specific gravity by 50% or more, compared with pre-treatment specific gravities, also supports the diagnosis of CDI, especially if urine specific gravity exceeds 1.030. There should be only minimal improvement in dogs and cats with primary NDI. Dogs and cats with psychogenic water consumption may exhibit a mild decline in urine output and water intake because the chronically low plasma osmolality tends to depress AVP production.
Pituitary or hypothalamic neoplasia should be considered in the older dog or cat diagnosed with CDI. A complete neurologic evaluation and diagnostic imaging (CT, MRI) of the hypothalamic and pituitary region may be warranted, especially if the owner is willing to consider radiotherapy should a tumor be identified. Similarly, a more complete evaluation of the kidney (e.g., renal biopsy) may be warranted in the older dog or cat tentatively considered to have primary NDI.
Table 1. Differential Diagnosis for Polydipsia and Polyuria
Richard W. Nelson, DVM, Diplomate ACVIM