Urine output in diabetes insipidus

INTRODUCTION

Diabetes insipidus (DI) is a disorder in which polyuria due to decreased collecting tubule water reabsorption is induced by either decreased secretion of antidiuretic hormone (central DI) or resistance to its renal effects (nephrogenic DI). In most patients, the degree of polyuria is primarily determined by the degree of ADH lack or resistance [1]. Thus, the urine output may range from 2 L/day with mild partial DI to over 10 to 15 L/day in patients with severe disease.

IMPORTANCE OF SOLUTE EXCRETION IN DIABETES INSIPIDUS

The determinants of the urine output differ in normal subjects and those with DI. The urine output in normals primarily reflects water intake, which leads to alterations in the plasma osmolality that are sensed by the osmoreceptors in the hypothalamus that regulate both ADH release and thirst. As an example, 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. (See "Chapter 6B: Antidiuretic hormone and water balance", section on 'Osmoreceptors'.)

There is, however, no direct way to sense changes in water intake in DI, where ADH release or effect is relatively fixed. Suppose that a patient has moderately severe nephrogenic DI which, 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 normal range at 750 mosmol/kg, then the daily urine output will be 5 L/day (750 ÷ 150 = 5).

One way to diminish the polyuria is to put the patient on a restricted salt and protein intake. 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. (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).

The importance of solute excretion probably explains the ability of concurrent cortisol deficiency to minimize the degree of polyuria in patients with combined anterior and posterior pituitary disease [2]. Lack of cortisol, via an unknown mechanism, leads to reductions in systemic blood pressure, cardiac output, and renal blood flow [3], all of which will tend to diminish the urine output. Lack of cortisol also may increase ADH release in patients with partial diabetes insipidus. (See "Hyponatremia and hyperkalemia in adrenal insufficiency".) Reversal of these effects via the administration of cortisol will unmask the DI, resulting in the rapid onset of polyuria [2].