Vasopressin response to osmotic stimulation in 18 young dogs with polyuria and polydipsia

Common disorders of water homeostasis leading to polyuria include a variety of endocrine, metabolic, and renal disturbances. After exclusion of most of these conditions, the diagnostic dilemma of differentiating between central diabetes insipidus, primary polydipsia, and nephrogenic diabetes insipidus may remain. Here, we report on 18 young dogs with polyuria that had been present in most cases since the dogs were puppies. The conditions were categorized according to the plasma vasopressin (VP) response to hypertonicity. The VP response to osmotic stimulation was tested by IV infusion of 20% NaCl for 2 hours. The VP response in all dogs was abnormal. Three categories could be distinguished: an exaggerated response (n = 3), a subnormal response (n = 4), and a nonlinear response with high plasma VP concentrations unrelated to increases in plasma osmolality (n = 11). The VP response to hypertonicity did not consistently distinguish among different clinical entities. In the 9 dogs with variations in urine osmolality compatible with primary polydipsia, exaggerated, subnormal, and nonlinear responses were observed. Examination of the present data questions the generally accepted notion that VP measurements during hypertonic saline infusion are the "gold standard" for the diagnostic interpretation of causes of polydipsia and polyuria. Studies of the peripheral reflection in plasma of the pulsatile VP release in healthy and polyuric individuals, with and without osmotic provocation, should be performed.     

Disturbed Vasopressin Release in 4 Dogs with So-Called Primary Polydipsia

Primary polydipsia is characterized by a marked increase in water intake and secondary polyuria, and in dogs often is described as a behavioral problem or a psychological disorder. We describe 4 dogs with primary polydipsia, diagnosed on the basis of a modified water deprivation test, in which further examination included serial measurements of urine osmolality (UOsm) and plasma vasopressin (VP) measurements during water deprivation and hypertonic saline infusion. The dogs, ranging in age from 4 months to 4 years, all were presented for evaluation of polyuria and polydipsia. Physical examination, routine blood chemistry, and urinalysis disclosed no specific cause for the polyuria and polydipsia. During serial measurements UOsm spontaneously reached high concentrations in 2 dogs, whereas in the other 2 dogs UOsm also fluctuated but on no occasion exceeded 1,000 mosm/kg. Primary polydipsia was diagnosed when UOsm exceeded 1,000 mosm/kg at the end of the modified water deprivation test and plasma osmolality did not exceed the upper limit of the reference range during testing. During water deprivation, plasma VP concentrations remained relatively low. The VP response to hypertonic saline infusion was abnormal, with an increased threshold value in 3 dogs, an increased sensitivity in 2 dogs, and an exaggerated response in 1 dog. It is concluded that some dogs fulfilling current criteria for primary polydipsia produce concentrated urine spontaneously throughout the day in a pattern similar to what has been observed in healthy pet dogs. This finding can be regarded as diagnostic and precludes the need for a water deprivation test. During water deprivation testing, all 4 dogs produced highly concentrated urine in the face of low basal plasma VP concentrations. The observed abnormal VP release in response to hypertonic stimulation may be interpreted as a primary disturbance in the regulation of VP secretion, although it might also be the result of overhydration caused by a primary abnormality in drinking behavior.     

Urinary aquaporin-2 excretion in dogs: a marker for collecting duct responsiveness to vasopressin

In humans, the urinary aquaporin-2 (U-AQP2) excretion closely parallels changes in vasopressin (VP) action and has been proposed as a marker for collecting duct responsiveness to VP. This report describes the development of a radioimmunoassay for the measurement of U-AQP2 excretion in dogs. In addition, the localization of AQP2 in the canine kidney was investigated by immunohistochemistry. Basal U-AQP2 excretion was highly variable among healthy dogs. Two hours after oral water loading, the mean U-AQP2/creatinine ratio decreased significantly from (231 +/- 30) x 10(-9) to (60 +/- 15) x 10(-9) (P = 0.01), while the median plasma VP concentration decreased from 4.2 pmol/l (range 2.2-4.8 pmol/l) to 1.2 pmol/l (range 1.0-1.9 pmol/l). Subsequent intravenous administration of desmopressin led to a significantly increased mean U-AQP2/creatinine ratio of (258 +/- 56) x 10(-9) (P = 0.01). Two hours of intravenous hypertonic saline infusion (20% NaCl, 0.03 ml/kg body weight/min) significantly increased the mean U-AQP2/creatinine ratio from (86 +/- 6) x 10(-9) to (145 +/- 23) x 10(-9) (P = 0.045), while the median plasma VP concentration increased significantly from 2.2 pmol/l (range 1.1-6.3 pmol/l) to 17.1 pmol/l (range 8.4-67 pmol/l) (P < 0.001). Immunohistochemistry revealed extensive labeling for AQP2 in the kidney collecting duct cells, predominantly localized in the apical and subapical region. As in humans, U-AQP2 excretion in dogs closely reflects changes in VP exposure. Urinary AQP2 excretion may become a diagnostic tool in dogs for the differentiation of polyuric conditions such as (partial) central or nephrogenic diabetes insipidus, primary polydipsia, and inappropriate VP release.     

Evaluation of a modified water-deprivation test for diagnosis of polyuric disorders in dogs.

A modified water-deprivation test was performed on 12 polyuric and 4 clinically normal dogs. Immediately after maximal urine osmolality had been achieved with water deprivation, antidiuretic hormone was injected to test further renal concentrating ability. The test provided accurate diagnosis of severe hypothalamic-neurohypophyseal diabetes insipidus in 3 dogs, partial diabetes insipidus in 2 dogs, and primary (psychogenic) polydipsia in 2 dogs. Five polyuric dogs with hyperadreno corticism had a response to the modified water-deprivation test similar to that of dogs with partial diabetes indipidus.     

Polyuria and Polydipsia and Disturbed Vasopressin Release in 2 Dogs With Secondary Polycythemia

In dogs, secondary polycythemia (SP) may be associated with polyuria and polydipsia (PU/PD). The pathogenesis of this PU/PD has not yet been explained. We hypothesized that hyperviscosity and increased blood volume in SP might affect vasopressin (VP) release, resulting in PU/PD. This hypothesis was tested in 2 dogs with SP caused by renal neo-plasia and PU/PD. Osmoregulation of VP release was studied by a modified water deprivation test and by investigating the VP response to hypertonic saline infusion.
Water deprivation test results were consistent with an inability to produce concentrated urine despite increasing plasma osmolality. During hypertonic saline infusion, the osmotic threshold of VP release was markedly increased in both dogs, resulting in a delayed VP response to increasing plasma osmolality. The sensitivity of VP release was low normal in both dogs. We conclude that blood hyperviscosity and increased blood volume led to impaired VP release and polyuria.     

Pulsatile secretion pattern of vasopressin under basal conditions, after water deprivation, and during osmotic stimulation in dogs

Measurement of plasma osmolality (Posm) and plasma vasopressin (VP) concentration in response to hypertonicity is regarded as the gold standard for the assessment of VP release in polyuric conditions. Yet the interpretation of the VP curve as a function of Posm may be hampered by the occurrence of VP pulses. To determine whether VP is secreted in a pulsatile fashion in the dog and whether stimulation of VP release changes the secretion pattern of VP, we measured VP at 2-min intervals for 2 h under basal conditions, after 12 h of water deprivation, and during osmotic stimulation with hypertonic saline (20%) in eight healthy dogs. Vasopressin was secreted in a pulsatile fashion with a wide variation in number of VP pulses, VP pulse duration, and VP pulse amplitude and height. After water deprivation, total and basal VP secretion, the number of significant VP pulses, as well as the pulse characteristics did not differ from the basal situation. During osmotic stimulation, there was a large increase in both basal and pulsatile VP secretion, and the number of VP pulses and VP pulse height and amplitude were significantly increased. The VP pulse amplitude correlated significantly with the basal plasma VP concentration during osmotic stimulation. It is concluded that VP is secreted in a pulsatile manner in healthy dogs. The basal and pulsatile VP secretion increases during osmoreceptor-mediated stimulation. The VP pulses may occur to the magnitude that they may be interpreted as erratic bursts, when occurring in the hypertonic saline infusion test.     

Transient diabetes insipidus in a dog with acromegaly

A nine-year-old female beagle with acromegaly and extreme polyuria and polydipsia during dioestrus is described. It was demonstrated that polyuria was related to an inadequate rise of arginine-vasopressin (AVP) levels after water deprivation and stimulation with hypertonic saline. Administration of AVP did not lead to a significant increase in urine osmolality or reduction of urine volume. Clinical signs, except for bony changes, completely disappeared following ovariohysterectomy.     

Nephrogenic diabetes insipidus in a 14-year-old gelding

Abstract

CASE HISTORY: A 14-year-old Cleveland Bay cross gelding was presented with severe urinary incontinence that had been present for 1 year, and chronic polydipsia and polyuria over 4 years. Water intake had been recorded as 240 L over a 24-hour period.

CLINICAL FINDINGS: The horse had marked urinary incontinence and polyuria and polydipsia. The urine was markedly hyposthenuric, but no abnormalities on urinalysis were detected. There were no other abnormal clinical or neurological signs. Haematological and serum biochemical examinations showed no abnormalities and ultrasonographic and endoscopic examination of the urinary tract did not reveal any abnormalities. The horse underwent a modified water deprivation test and failed to concentrate its urine after 5 days. 1-desamino-8-d-arginine vasopressin (DDAVP) was administered I/V but the urine remained isosthenuric with a specific gravity of 1.010.

DIAGNOSIS: Nephrogenic diabetes insipidus. A definitive cause of the urinary incontinence was not found but overflow incontinence was considered a possibility.

CLINICAL RELEVENCE: Despite being a rare condition in the horse diabetes insipidus should be considered in cases of severe polydipsia and polyuria in mature horses.     

Partial deficiency of antidiuretic hormone in a cat

Marked polydipsia and polyuria developed subsequent to trauma in a 1 1/2-year-old male Abyssinian cat. Diabetes insipidus was suspected, inasmuch as intramuscualr vasopressin administration resulted in amelioration of polydipsia and polyuria. However, hypertonic (3%) saline solution given intravneously resulted in anuria, an indication of antidiuretic hormone activity. Polyuria and polydipsia were abolished by oral chlorpropamide therapy, which was indirect evidence for partial deficiency of antidiuretic hormone.     

Concurrent central diabetes insipidus and panhypopituitarism in a German shepherd dog

This report describes a German shepherd dog that was presented with proportionate dwarfism and coat changes typical of hypopituitarism but that was also profoundly polydipsic and polyuric. Investigations established a diagnosis of concurrent central diabetes insipidus. Treatment with desmopressin was successful in managing the polyuria and polydipsia.     

Central diabetes insipidus in five cats: clinical presentation, diagnosis and oral desmopressin therapy

Five cases of central diabetes insipidus (CDI) in domestic shorthair cats are described. All cats were under 3 years of age at the onset of clinical signs, and outdoor or outdoor/indoor cats, in which a prior trauma was either present or possible. The history included polydipsia and polyuria, and physical examination abnormalities included urinary bladder distention and dehydration. All cats had hyposthenuria with a urine specific gravity between 1.003 and 1.006. The diagnosis was confirmed by an observed inability to concentrate urine during a water deprivation test or compatible serum osmolality, followed by an increase in urine concentration after desmopressin administration. All cats in this report were treated successfully with oral desmopressin. The dose (25-50 microg q8-12h) and the response to therapy were variable. Oral desmopressin administration may serve as an effective alternative route for cat owners who find the conjunctival or nasal application of the solution an inconvenient mode of therapy.     

Renal Effects of Long Term Administration of Triamcinolone Acetonide in Normal Dogs

Triamcinolone acetonide was administered in excessive dosage to dogs to study the renal mechanism responsible for polyuria which is a clinically undesirable side effect of long term glucocorticoid therapy.

Polyuria occurred coincident with a significant increase in urinary solute output. Although continuous administration of triamcinolone acetonide at 0.1 or 0.2 mg/lb/day caused a small but significant increase in creatinine output, the primary mechanism for the polyuria was increased solute excretion. Associated with the polyuria was pronounced hyperphagia and polydipsia. The cause of the hyperphagia was not established. The increase in electrolyte excretion caused by this synthetic steroid was probably compensated for by the hyperphagia. Because all the dogs showed muscle weakness and loss of body condition, it is likely that alteration in protein and amino acid metabolism was responsible for the hyperphagia.

     

Water transport in the kidney and nephrogenic diabetes insipidus

Nephrogenic diabetes insipidus is caused by an inability of the kidney to concentrate urine despite adequate concentration of vasopressin in blood and is characterized by polyuria, polydipsia, and hyposthenuria in the presence of plasma hyperosmolality. Nephrogenic diabetes insipidus is the result of defects in water homeostasis in the kidney. Nephrogenic diabetes insipidus occurs when the kidneys cannot or do not respond to vasopressin. There are 2 categories of nephrogenic diabetes insipidus. Congenital nephrogenic diabetes insipidus is a rare, inherited, irreversible cause of polyuria and polydipsia in humans that is even rarer in animals. Acquired nephrogenic diabetes insipidus is more common and is often secondary to illness or medication that interferes with the action of vasopressin in the renal tubules. Unlike congenital nephrogenic diabetes insipidus, acquired or secondary nephrogenic diabetes insipidus is often reversible with correction of the associated or causative problem.     

Polyuria and polydipsia. Diagnostic approach and problems associated with patient evaluation.

Primary disorders of water balance (central diabetes insipidus [DI], nephrogenic DI, and psychogenic polydipsia) should always be considered in the differential diagnosis of polyuria and polydipsia. In general, animals with these disorders have only one laboratory abnormality: a low urine specific gravity. In most instances, the more common causes of polyuria and polydipsia (e.g., hyperadrenocorticism, chronic renal failure, pyelonephritis, pyometra) have specific and obvious abnormalities associated with the complete blood cell count, the serum chemistry profile, and urinalysis. In some cases, however, a low urine specific gravity may be the only abnormality associated with these more common findings. The workup for polyuria and polydipsia can be tedious, time-consuming, expensive, confusing, and not without significant patient morbidity, especially in those cases with normal or near-normal blood work. This article focuses on the diagnostic approach and problems associated with diagnostic testing in patients with disorders of water balance.     

Diagnostic approach to polydipsia and polyuria

A variety of metabolic disturbances account for the majority of cases of polydipsia and polyuria. This chapter presents guides to differential diagnosis as well as a discussion of the etiology and clinical features of the primary causes--central diabetes insipidus, nephrogenic diabetes insipidus, and psychogenic polydipsia.     

Transient renal tubulopathy in a Labrador retriever.

A four-month-old male Labrador retriever was presented for polyuria, polydipsia and persistent euglycaemic glucosuria. On referral, diagnostic tests demonstrated abnormal fractional excretions of electrolytes, increased urinary excretion of selected amino acids, mild renal tubular acidosis and mild proteinuria, indicating renal tubular dysfunction. Pyelonephritis was suspected and potentiated amoxycillin was administered. On re-evaluation at six months of age, the dog was no longer polyuric or polydipsic and the metabolic abnormalities associated with the tubulopathy had resolved. Transient Fanconi's syndrome has not previously been reported in small animals. This report demonstrates the potential for recovery of function in cases presenting with renal tubulopathies.     

Cryptococcal pyelonephritis in a dog

A 5-year-old castrated male Golden Retriever was evaluated for polyuria, polydipsia, and progressive regurgitation thought to be a result of bacterial pyelonephritis and megaesophagus. Bacteriologic culture of urine failed to yield clinically relevant growth, and results of a urine sediment examination were normal. With time, intention tremors and progressive neurologic dysfunction were also observed. At necropsy, a diagnosis of cryptococcal disease was confirmed histologically and immunohistochemically. Findings in the dog of this report were indicative of nephrogenic diabetes insipidus with polyuria and polydipsia caused by cryptococcal pyelonephritis. Neurologic manifestations of systemic cryptococcus infection included megaesophagus, esophageal hypomotility, and regurgitation attributed to localization of cryptococcal organisms in the brain stem in the region of the dorsal motor nucleus of the vagus nerve. To the authors' knowledge, this is the first report of polyuria secondary to cryptococcal pyelonephritis.     

Congenital central diabetes insipidus in two sibling Afghan hound pups

Congenital central diabetes insipidus was determined to be the cause of polydipsia and polyuria in sibling pups. Both pups were lacking adequate plasma arginine vasopressin concentration, compared with that in control dogs. Microscopic abnormalities were confined to the brain and pituitary gland in one pup. Without breeding trials of these dogs or their relatives, it cannot be determined whether the cause was familial.