INTRODUCTION — Arginine vasopressin disorders (formerly, diabetes insipidus [DI]) are disorders in which polyuria due to decreased collecting tubule water reabsorption is induced by either decreased secretion of antidiuretic hormone (ADH; vasopressin deficiency, formerly called central DI) or resistance to its kidney effects (vasopressin resistance, formerly called nephrogenic DI) . In most patients, the degree of polyuria is primarily determined by the degree of ADH deficiency or resistance [2,3]. Thus, the urine output may range from 2 L/day with mild partial deficiency or resistance to over 10 to 15 L/day in patients with severe disease.
Determinants of the urine output in patients with arginine vasopressin disorders will be discussed here. The causes, diagnosis, treatment of these disorders are presented elsewhere:
DETERMINANTS OF URINE OUTPUT — The determinants of the urine output differ between individuals with and without an arginine vasopressin disorder. The urine output in those without the disorder primarily reflects water intake, which leads to alterations in the plasma osmolality that are sensed by the osmoreceptors in the hypothalamus that regulate both antidiuretic hormone (ADH) release and thirst [4-7]. In addition to central osmoreceptors, peripheral neurons that innervate hepatic blood vessels detect osmotic shifts in portal blood and modulate ADH release, a process that is mediated partly by secretion of vasoactive intestinal peptide after water ingestion . The salt and water content of gastrointestinal fluid is sensed and transmitted to the hypothalamic thirst nuclei influencing drinking behaviour . (See "General principles of disorders of water balance (hyponatremia and hypernatremia) and sodium balance (hypovolemia and edema)", section on 'Regulation of plasma tonicity'.)
Normally, an increase in water intake sequentially lowers the plasma osmolality, decreases ADH secretion, and reduces collecting tubule permeability to water; as a result, the excess water is rapidly excreted in a dilute urine. However, changes in water intake do not result in appropriate changes in urine output in patients with an arginine vasopressin disorder, because ADH release or effect is relatively fixed. Instead, urine output is relatively constant, regardless of water intake, unless dietary salt and/or protein intake change. Suppose, for example, that a patient has moderately severe arginine vasopressin resistance that, because of the ADH resistance, will not respond to hormone replacement. The urine osmolality in this patient cannot be raised above 150 mosmol/kg (normal maximum urine osmolality is 900 to 1200 mosmol/kg). In this setting, the excretion of solutes (primarily sodium and potassium salts and urea) is the major determinant of the urine output. If solute excretion is in the usual range (eg, 750 mosmol/kg), then the daily urine output will be 5 L/day (750 ÷ 150 = 5). In this patient, urine output will rise if solute excretion is increased and fall if solute excretion is reduced.
Thus, one way to diminish polyuria in patients with vasopressin deficiency or resistance is to restrict salt and protein intake, which in turn will reduce the solute load and solute excretion. If, for example, solute excretion fell to 525 mosmol/day, the urine output would fall to 3.5 L/day. On the other hand, the degree of polyuria can be enhanced by increasing solute excretion, as often occurs with high-protein hyperalimentation in hospitalized patients. Each gram of protein catabolized produces approximately 170 mg of urea. Thus, a protein load of 70 g (1 g/kg of body weight in a 70 kg adult) will generate approximately 11.2 g of urea nitrogen, which corresponds to approximately 400 mmol or mosm of urea. At a typical urine osmolality of 300 to 500 mosmol/kg in solute diureses, an increased urea excretion of this magnitude will require a urine output of 0.8 to 1.3 liters.
Similar considerations concerning the role of solute intake apply when ADH secretion is relatively fixed at a high level in the syndrome of inappropriate ADH secretion . (See "Treatment of hyponatremia: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) and reset osmostat", section on 'High solute intake'.)
Cortisol deficiency may minimize the degree of polyuria in patients with combined anterior and posterior pituitary disease . Lack of cortisol, via an unknown mechanism, leads to reductions in systemic blood pressure, cardiac output, and renal blood flow , all of which will tend to diminish the urine output. Lack of cortisol also may increase ADH release in patients with partial vasopressin deficiency (see "Hyponatremia and hyperkalemia in adrenal insufficiency"). Reversal of these effects via the administration of cortisol will unmask the vasopressin deficiency, resulting in the rapid onset of polyuria .
Development of hyperglycemia and glucosuria — The polyuria in arginine vasopressin disorders is typically matched by an equivalent increase in water intake via stimulation of thirst. Some patients cannot take fluids orally and are treated with large volumes of intravenous fluid replacement, usually with dextrose and water solutions. This regimen can induce marked hyperglycemia due to the delivery of glucose at a rate that exceeds endogenous metabolic capacity for glucose even in nondiabetics . The associated glucosuria, acting as an osmotic diuretic, can lead to a clinically confusing increase in the urine output that is now ADH resistant. In this setting, however, the urine osmolality is typically above 300 mosmol/kg (if ADH has been given) with the polyuria being driven by the solute load. The administration of insulin to correct the hyperglycemia will restore ADH sensitivity. Glucosuria from empagliflozin, a sodium glucose cotransporter 2 inhibitor, has been used successfully to increase osmotic diuresis and improved plasma sodium in patients with SIADH . (See "Evaluation of patients with polyuria", section on 'Solute (osmotic) diuresis'.)
PREGNANCY — The polyuria in incomplete arginine vasopressin deficiency (ie, partial deficiency of antidiuretic hormone [ADH]) is typically exacerbated by pregnancy. The placenta releases vasopressinases that enhance the catabolism of ADH. This is of no clinical importance in healthy females but can lead to polyuria when secretory reserve is diminished due to underlying vasopressin deficiency. Treatment is most effective with the analog, desmopressin, which is resistant to the vasopressinases. (See "Maternal adaptations to pregnancy: Renal and urinary tract physiology".)
●Arginine vasopressin disorders are those in which polyuria due to decreased collecting tubule water reabsorption is induced by either decreased secretion of antidiuretic hormone (ADH; vasopressin deficiency, formerly central DI) or resistance to its kidney effects (vasopressin resistance, formerly nephrogenic DI). In most patients, the degree of polyuria is primarily determined by the degree of ADH deficiency or resistance. (See 'Introduction' above.)
●In patients with arginine vasopressin disorders, urine output is relatively constant, regardless of water intake, unless dietary salt and/or protein intake change. Urine output will rise if solute excretion is increased and fall if solute excretion is reduced. Thus, one way to diminish polyuria in patients with arginine vasopressin disorders is to restrict salt and protein intake, which in turn will reduce the solute load and solute excretion. (See 'Determinants of urine output' above.)
●If patients with arginine vasopressin disorders are treated with large volumes of intravenous fluid replacement, usually with dextrose and water solutions, the delivery of glucose may exceed endogenous metabolic capacity, and the associated glucosuria, acting as an osmotic diuretic, can lead to a clinically confusing increase in the urine output that is resistant to ADH. (See 'Development of hyperglycemia and glucosuria' above.)
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