Polyuria and Polydipsia

Harold C. Schott II • Theresa L. OIhvett •

Alexandra J. Burton

Polyuria and polydipsia (PU/PD) are defined as urine output in excess of 50 mL/kg/day (PU) and fluid intake of more than 100 mL/kg/day (PD).^1,2 These values equate to production of 25 L of urine and consumption of 50 L of water for a 500-kg horse.

PolyuriaZPolydipsia With Pituitary Pars Intermedia Dysfunction

Adenoma of the pituitary pars intermedia results in PPID (formerly termed equine Cushing's disease), with elevated adrenocorticotrophic hormone (ACTH) and hyperadrenocorti- cism. The syndrome has been well recognized and clinically characterized in equids for more than 40 years and is common in older horses (see Chapter 41).^6,7 Generally, the most con­sistently reported clinical signs in horses are delayed shedding, hirsutism, and muscle wasting. Although a degree of PU/PD is nearly always present in horses with uncontrolled PPID, it may not be readily noted or reported by the owner/trainer.

Several mechanisms may lead to PU/PD in horses with PPID. Firstly, PU may be the result of an osmotic diure­sis. The renal threshold for glucose in horses (≈150 to 175 mg/dL) appears to be lower than in small animals.⁸ When plasma glucose concentration exceeds the renal threshold, the resultant glucosuria can lead to an osmotic diuresis. Although often implicated as the cause of PU/PD in horses with PPID, hyperglycemia and glucosuria are not always present with the disease and are often only found in more advanced cases or those with concurrent equine metabolic syndrome (EMS). A second mechanism implicated in the development of PU with PPID is antagonism of the action of antidiuretic hormone (ADH) on the collecting ducts by excess cortisol. Vasopressin, arginine vasopressin (AVP), and argipressin are all other names for ADH. Although frequently cited as the mechanism of PU in canine hyperadrenocorticism, experimental evidence to support this mechanism is lacking in both dogs and horses. There is considerable species heterogeneity in the effects of corticoids on ADH activity, and in some species, a primary dipsogenic (thirst-stimulating) effect may be more important. Growth of the adenoma (as PPID becomes more advanced) may lead to impingement on the posterior pituitary and hypothalamic nuclei (located immediately dorsal to the pituitary gland), the sites of ADH storage and production, respectively. Decreased ADH production and release would result in central DI as a third mechanism for PU. Finally, if not body clipped, horses with hirsutism will become excessively hot and sweaty in warm climates or during exercise and thus PD may develop as a normal physiologic response to fluid loss in sweat. Therefore, PU/PD seen in horses with PPID is likely the combined result of several mechanisms.

Primary Psychogenic Polydipsia

Primary, or “psychogenic,” PD is rare but probably the most common cause of PU/PD in adult horses for which clients will have a primary complaint of excessive urination.^2,4,9 This is because the magnitude of their PU/PD is typically dramatic, with owners reporting that horses drink two to three times more water than other horses on the premises, and stalls can be flooded with urine. Horses with this problem are generally in good body condition and not azotemic but will be hypostenuric with a USG 1.020 USG) after 24 hours of water deprivation, a modified water deprivation test may be tried. During the modified water deprivation test, water intake is restricted to about 40 mL/kg/day, for 3 to 4 days. By the end of this period, USG should exceed 1.025 in a horse that has had medullary washout. If USG remains in the isosthenuric range (1.008 to 1.014), the polyuric horse should be further evaluated for early chronic renal failure, in which the ability to concentrate urine may be compromised before the onset of azotemia. In theory, this could only occur when 65% to 75% of functional nephrons have been lost. Subtle signs of decreased performance and mild weight loss would also support early renal failure.

Management of horses with primary PD is empirical. Because primary PD is a diagnosis of exclusion, once it has been established that the horse does not have significant renal disease, it is safe to continue restricting water intake to meet mainte­nance, work, and environmental requirements of the horse. In addition, steps should be taken to improve the attitude of the horse by reducing boredom or any other potential stress trigger factors. Increasing the amount of exercise and turning the horse out to pasture are possible options, along with provid­ing a companion or diversions in the stall. Increasing the frequency of feedings or amount of roughage in the diet may increase time spent eating and thereby reduce the habitual drinking.

An occasional case of primary PD may be attributed to “psychogenic salt eating” (excessive salt consumption) and is manifested by an increased fractional sodium clearance.^3,4 However, salt intake may have to exceed 5% to 10% of dry matter intake before significant PU/PD develops.^12,13 Successful management consists of limiting water intake and preventing or limiting access to excess salt. However, this must be bal­anced against any salt loss via sweat due to very high ambient temperatures and exercise. In these situations the horse may need to be allowed some (regulated) salt and mineral lick consumption to replace high losses in sweat. In addition, in one author’s experience (AJB) removal of a salt block/lick from a psychogenic salt eater can lead to consumption of excessive amounts of soil/dirt instead, as salt is a natural component of soil. This could potentially lead to sand colic, dependent on the soil composition.

Diabetes Insipidus

Diabetes insipidus (DI) is generally rare in horses. It may be divided into two types: inadequate secretion of ADH (neurogenic [central] DI) or decreased sensitivity of the renal epithelial cells of the collecting ducts to circulating ADH or loss of ADH receptors on these cells (nephrogenic DI).^1,2,14 With both forms of DI, dramatic PU/PD may be reported and affected animals fail to concentrate urine in the face of water deprivation.

In human patients, neurogenic DI is the more common form of DI, with both hereditary and acquired forms described.¹⁵ In two well-documented cases of neurogenic DI diagnosed in adult horses, neither horse could concentrate urine in response to water deprivation, but administration of exogenous ADH resulted in an increase in USG and a decrease in urine volume.^16,17 In a Welsh pony in which the condition was considered idiopathic, the absence of an increase in plasma ADH concentration after water deprivation further supported a diagnosis of neurogenic DI.¹⁶ Acquired neurogenic DI secondary to encephalitis was confirmed histologically in the other horse.¹⁷ Presumed congenital neurogenic DI has also been described in a 10-day-old Friesian colt with tachypnea and polyuria, documented by a modified fluid deprivation test and a rise in plasma ADH (vasopressin) after treatment with exogenous synthetic ADH (desmopressin).¹⁸ Neurogenic DI has also been reported in a 20-year-old gelding with PPID and PU/PD that was normoglycemic, did not respond to a water deprivation test, but did respond to desmopressin administration.¹⁹

Nephrogenic DI is most often a familial disorder in humans, with an X-linked semirecessive mode of inheritance.¹⁵ Therefore, the disorder is carried by females and expressed in male off­spring.

After determining that an equine patient with PU/PD is not azotemic, the initial diagnostic test to differentiate DI from primary PD is a water deprivation test.^2,14 However, horses with suspected DI should be monitored closely during water deprivation because horses that do have DI will continue to excrete excess water in the face of water deprivation. As a result, they may become substantially dehydrated (10% to 15%) within the first 12 hours of water deprivation. When a patient fails to concentrate urine during water deprivation, neurogenic DI can be differentiated from nephrogenic DI by measuring plasma ADH (AVP) concentration or by administration of synthetic ADH (aqueous synthetic vasopressin or 1-desamino-8-d-arginine vasopressin [DDAVP or desmopressin] may be used).^2,14 After administration of exogenous ADH, if USG rises in response, then this indicates neurogenic DI, whereas a lack of urine 2 14 16 21 concentration indicates nephrogenic DI.^2,14^{, 21}

Treatment of DI is directed at managing PU/PD. With neurogenic DI, hormone replacement therapy with desmopres­sin (DDAVP), a potent ADH analog administered as a nasal spray or orodispersible tablet (humans), eyedrops (dogs) or orally (cats), has been a successful treatment for neurogenic DI.^22,23 There is a report of a 10-day-old Friesian colt with suspected neurogenic DI being successfully temporarily treated using human desmopressin acetatehydrate nasal drops admin­istered as eye drops.¹⁸ With nephrogenic DI, hormone replace­ment therapy is ineffective, and the only practical form of treatment for many years has been to restrict sodium and water intake and administer thiazide diuretics.

Diabetes Mellitus

Diabetes mellitus (DM) is a state of chronic hyperglycemia usually accompanied by glucosuria. The resultant osmotic diuresis by glucose causes PU/PD. In one horse, DM resulted in water intake in excess of 80 L/day.²⁵ Although generally rare in horses, there are several reports of type I and type II (more common) DM.^25-29 Lately, equine DM has received more atten­tion, probably due to increasing recognition and understanding of the equine endocrinopathies equine metabolic syndrome (EMS) and PPID, both of which may result in persistent chronic hyperglycemia in a subset of severe cases. In EMS, peripheral insulin resistance and subsequent hyperinsulinemia are classic features. Occasionally, the pancreas becomes “exhausted” with pancreatic β cell dysfunction (inadequate insulin production), with the result being persistent hyperglycemia and DM.^29,30 Blood glucose concentrations are often mildly to moderately elevated in horses with PPID due to elevated ACTH and cortisol, but these horses do not usually develop chronic persistent hyperglycemia that exceeds renal threshold until PPID is quite advanced. However, if the horse has prior and/ or concurrent EMS, then significant, persistent hyperglycemia is much more likely to occur and DM to develop. As discussed previously, PPID may also lead to PU/PD by a variety of other mechanisms.

Iatrogenic Polyuria

The most obvious iatrogenic cause is fluid therapy, for which PU is a desired response. Diuretics such as furosemide also cause intentional PU in horses. Polyuria has also been observed with exogenous corticosteroid administration, although the mechanism remains unclear. Humans and dogs appear to experi­ence a potent thirst response to exogenous corticosteroids, so PD may be an important cause of the PU observed. Further, in horses receiving chronic dexamethasone treatment for immune- mediated disorders, profound glucosuria (2 to 3 g/dL) may be observed and could lead to an osmotic diuresis. A transient diuresis or PU accompanies sedation with the α₂-agonists xylazine and detomidine, even when water has been withheld for 24 hours previously.^31,32 Although these agents also cause transient hyperglycemia and occasional glucosuria, a more likely mechanism for PU is existence of α₂-adrenoreceptors on collecting duct epithelial cells. Activation of these receptors is another mechanism by which the action of ADH can be antagonized.³³