Studies on the role of vasopressin in canine polyuria

Abstract

Observations in 89 healthy dogs indicate that the ranges of urine specific gravity (1.006 - >1.050) and urine osmolality (Uosm, 161 – 2830 mOsm/kg) are much larger than previously thought. In addition to the large interindividual variation in Uosm, in some dogs Uosm varied widely during the day with two- to three-fold increases or decreases in Uosm often occurring within two hours. Because of these wide spontaneous fluctuations in Uosm, documentation of polyuria cannot be based on the measurement of a low Uosm in one single urine sample. Vasopressin (VP) release in dogs with secondary polycythaemia due to renal neoplasm is impaired during hypertonic saline infusion, with a markedly increased osmotic threshold and a low sensitivity of the response. Primary polydipsia is characterised by a marked increase in water intake that cannot be explained as a compensatory mechanism for excessive fluid loss. Serial measurements of Uosm (collected every 2 hours for 24 hours, with an interval of 4 hours during the night) demonstrated large fluctuations in Uosm in several of the dogs fulfilling the criteria of primary polydipsia with some Uosm values exceeding 1000 mOsm/kg. It can be concluded that a water deprivation test is not needed in all polyuric dogs. When pronounced fluctuations are found in Uosm during serial measurements and some Uosm values exceed 1000 mOsm/kg, the diagnosis of primary polydipsia seems justified. In all dogs with primary polydipsia the VP response to osmotic stimulation was disturbed, which 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 behaviour. After exclusion of most of the conditions leading to polyuria, there may remain the diagnostic dilemma of differentiating between central diabetes insipidus, primary polydipsia, and nephrogenic abnormalities. The most powerful diagnostic tool for differentiation of these conditions is the hypertonic saline infusion test, with measurement of plasma osmolality (Posm) and plasma VP concentration. Eighteen young polyuric dogs were categorised according to the plasma VP response to hypertonic saline infusion. Three categories could be distinguished: (a) a hyperresponse, (b) a hyporesponse, and (c) a non-linear response with high VP values unrelated to increases in Posm. The high VP values may represent bursts of VP release, similar to those that occur in the syndrome of inappropriate VP secretion (SIADH), or they may reflect the (normal) pulsatile VP release. As the VP response to hypertonic saline infusion did not consistently distinguish between the different clinical conditions (e.g. inadequate concentrating ability and primary polydipsia), the data question the generally accepted notion that VP measurements during hypertonic saline infusion are the "gold standard" for the diagnosis of polyuric conditions. In the dog, VP is secreted in a pulsatile fashion with a wide variation in the number of VP pulses, VP pulse duration, and VP pulse amplitude and height. Mild dehydration does not influence VP pulsatile secretion, whereas osmotic stimulation significantly increases basal and pulsatile VP release in the dog. The pulsatile secretion pattern of VP in dogs may explain part of the non-linear VP responses to osmotic stimulation, occurring in some polyuric dogs as described above. The occurrence of spontaneous VP pulses may severely hamper the interpretation of the curve describing the relationship between Posm and plasma VP concentration during osmotic stimulation. A radioimmunoassay for the measurement of urinary aquaporin-2 (U-AQP2) excretion in dogs is described. Basal U-AQP2 excretion in healthy dogs, expressed as the U-AQP2/creatinine ratio, varied similarly to the large individual variation in U-AQP2 excretion found in humans. Urinary AQP2 excretion in dogs closely reflects changes in collecting duct exposure to VP, as demonstrated by the responses to oral water loading, osmotic stimulation, and intravenous desmopressin administration. As in humans, U-AQP2 excretion may be of use as a diagnostic tool in canine polyuria, for the differentiation of (partial) central diabetes insipidus, (partial) nephrogenic diabetes insipidus, primary polydipsia, and SIADH.