Polyuria is urine output of > 3 L/day; it must be distinguished from urinary frequency, which is the need to urinate many times during the day or night but in normal or less-than-normal volumes. Either problem can include nocturia.
Pathophysiology of Polyuria
Water homeostasis is controlled by a complex balance of water intake (itself a matter of complex regulation), renal perfusion, glomerular filtration and tubular reabsorption of solutes, and reabsorption of water from the renal collecting ducts.
When water intake increases, blood volume increases and blood osmolality decreases, decreasing release of antidiuretic hormone (ADH; also referred to as arginine vasopressin) from the hypothalamic-pituitary system. Because ADH promotes water reabsorption in the renal collecting ducts, decreased levels of ADH increase urine volume, allowing blood osmolality to return to normal.
Additionally, high amounts of solutes within the renal tubules cause a passive osmotic diuresis (solute diuresis) and thus an increase in urine volume. The classic example of this process is the glucose-induced osmotic diuresis in uncontrolled diabetes mellitus, when high urinary glucose levels (> 250 mg/dL [13.88 mmol/L]) exceed tubular reabsorption capacity, leading to high glucose levels in the renal tubules; water follows passively, resulting in glucosuria and increased urine volume. Glucose-induced osmotic diuresis in diabetes mellitus is further increased with use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) that lower plasma glucose levels by inhibiting renal glucose reabsorption and increasing renal glucose excretion.
Therefore, polyuria results from any process that involves 1 or more of the following:
Etiology of Polyuria
The most common cause of polyuria in adults is
Taking diuretics
The most common cause of polyuria (see table Some Causes of Polyuria) in adults and children is
Uncontrolled diabetes mellitus
In the absence of diabetes mellitus, the most common causes are
Some Causes of Polyuria
Cause | Suggestive Findings | Diagnostic Approach* |
|---|---|---|
Water diuresis† | ||
| Abrupt or chronic onset of thirst and polyuria Sometimes follows trauma, pituitary surgery, or hypoxic or ischemic cerebrovascular insult or occurs during the first few weeks of life | Laboratory tests Water deprivation test with ADH challenge ADH measurement when diagnosis remains unclear |
| Gradual onset of thirst and polyuria in a patient with:
| Laboratory tests Water deprivation test with ADH challenge |
Polydipsia
| Anxious, middle-aged woman History of psychiatric illnesses Infiltrating lesions of the hypothalamus (usually sarcoidosis) | Laboratory tests Water deprivation test with ADH challenge |
Excessive hypotonic IV fluid administration | Hospitalized patient receiving IV fluids Possibly edema | Resolution after fluids stopped or rate of administration decreased |
Diuretic use | Recent initiation of diuretic for volume overload (eg, due to heart failure or peripheral edema) Patients who are likely to surreptitiously use diuretics for weight loss (eg, those with eating disorders or concerns about weight, athletes, adolescents) | Clinical evaluation |
Adipsic diabetes insipidus (ADI) (a hypothalamic disorder characterized by absent thirst from loss of osmoreceptor function and polyuria from AVP deficiency accompanied byhypernatremia) | Polyuria without excessive thirst Sometimes lesions in the hypothalamic region, such as a germinoma or craniopharyngioma, or recent anterior communicating artery repair | Sometimes hyperosmolality (eg, 300 to 340 mOsm/kg [or mmol/kg]) and hypernatremia without excessive thirst |
Gestational diabetes insipidus (resulting from increased ADH metabolism) | Polydipsia (with excessive thirst) and polyuria that develop for the first time during the third trimester | Inappropriately normal plasma sodium (normally decreases by about 5 mEq/L [or mmol/L] in late pregnancy) with urine osmolality lower than plasma osmolality Resolution 2–3 weeks postpartum |
Solute diuresis† | ||
Uncontrolled diabetes mellitus | Thirst and polyuria in a young child or in an obese adult with family history of type 2 diabetes | Finger-stick glucose measurement |
Isotonic or hypertonic saline infusions | Hospitalized patient receiving IV fluids | Laboratory tests (eg, 24-hour urine collection showing total osmole excretion [osmolality × urine volume]) Stopping or slowing rate of administration (to confirm that polyuria resolves) |
High-protein tube feedings | Any patient receiving tube feedings | Switching to tube feedings with lower protein content (to confirm that polyuria resolves) |
Relief of urinary tract obstruction | Polyuria after bladder catheterization in a patient with bladder outlet obstruction | Clinical evaluation |
* Most patients should have measurement of urine and plasma osmolarity and serum sodium. | ||
† Urine osmolality is typically < 300 mOsm/kg (300 mmol/kg) in water diuresis and > 300 mOsm/kg (300 mmol/kg) in solute diuresis. | ||
ADH = antidiuretic hormone. | ||
Patients recovering from oliguric acute kidney injury can have an osmotic diuresis.
Evaluation of Polyuria
History
History of present illness should include the amounts of fluid consumed and voided to distinguish between polyuria and urinary frequency. If polyuria is present, patients should be asked about the age at onset, rate of onset (eg, abrupt vs gradual), and any recent clinical factors that may cause polyuria (eg, IV fluids, tube feedings, resolution of urinary obstruction, resolving acute kidney injury, stroke, head trauma, surgery). Patients should be asked about their degree of thirst.
Review of systems should seek symptoms suggesting possible causes, including dry eyes and dry mouth (Sjögren syndrome) and weight loss and night sweats (cancer).
Past medical history should be reviewed for conditions associated with polyuria, including diabetes mellitus, psychiatric disorders, sickle cell disease, sarcoidosis, amyloidosis, and hyperparathyroidism. A family history of polyuria and excessive water drinking should be noted. Medication history should note use of any medications associated with (see table Some Causes of Polyuria) and agents that increase urine output (eg, diuretics, alcohol, caffeinated beverages).
Physical examination
The general examination should note signs of obesity (as a risk factor for type 2 diabetes mellitus) or undernutrition or cachexia that might reflect an underlying cancer or an eating disorder plus surreptitious diuretic use.
The head and neck examination should note dry eyes or dry mouth (Sjögren syndrome). Skin examination should note the presence of any hyperpigmented or hypopigmented lesions, ulcers, or subcutaneous nodules that may suggest sarcoidosis. Comprehensive neurologic examination should note any focal deficits that suggest an underlying neurologic insult and assess mental status for indications of a thought disorder. Volume status should be assessed. Extremities should be examined for edema.
Red flags
The following findings are of particular concern:
Abrupt onset
Onset during the first few years of life
Night sweats, cough, and weight loss, especially when there is an extensive smoking history
Psychiatric disorder
Interpretation of findings
History can often distinguish polyuria from frequency, but rarely a 24-hour urine collection may be needed.
Clinical evaluation may suggest a cause (see table Some Causes of Polyuria), but testing is usually necessary. is suggested by a history of cancer or chronic granulomatous disease (due to hypercalcemiasickle cell disease, renal amyloidosis, sarcoidosis, Sjögren syndrome) that have manifestations that are often more prominent than and precede the polyuria.
Abrupt onset of polyuria at a precise time suggests , as does preference for extremely cold or iced water. Onset during the first few years of life is typically related to inherited central or or uncontrolled type 1 diabetes mellitus. Polyuria caused by solute diuresis is suggested by a history of diabetes mellitus. Psychogenic polydipsia is more common in patients with a history of a psychiatric disorder (primarily bipolar disorder, or schizophrenia) rather than as an initial manifestation.
Testing
Once excess urine output has been verified by history or measurements, serum or fingerstick glucose determination should be done to rule out uncontrolled diabetes.
If hyperglycemia is not present, then testing is required:
Serum and urine chemistries (electrolytes, calcium)
Serum and urine osmolality and sometimes plasma antidiuretic hormone (ADH) level
These tests look for hypercalcemia, hypokalemia (due to surreptitious diuretic use), and hypernatremia or hyponatremia:
Hypernatremia (sodium > 142 mEq/L [142 mmol/L]) suggests excess free water loss due to central or nephrogenic diabetes insipidus.
Hyponatremia (sodium < 137 mEq/L [137 mmol/L]) suggests excess free water intake secondary to polydipsia.
Urine osmolality is typically < 300 mOsm/kg (300 mmol/kg) with water diuresis and > 300 mOsm/kg (300 mmol/kg) with solute diuresis.
If the diagnosis remains unclear, then measurement of serum and urine sodium and osmolality in response to a water deprivation test and exogenous ADH administration should be done. Because serious dehydration may result from this testing, the test should be done only while patients are under constant supervision; hospitalization is usually required. Additionally, patients in whom psychogenic polydipsia is suspected must be observed to prevent surreptitious drinking.
Various protocols can be used in water deprivation tests. Each protocol has some limitations. Typically, the test is started in the morning by weighing the patient, obtaining venous blood to determine serum electrolyte concentrations and osmolality, and measuring urine osmolality. Voided urine is collected hourly and its osmolality is measured. Dehydration is continued until orthostatic hypotension and postural tachycardia appear, ≥ 5% of the initial body weight has been lost, or the urinary concentration does not increase >
A normal response produces maximum urine osmolality after dehydration (>
In ,argininevasopressin deficiency vs 15 to 45% with partial argininevasopressin deficiency.
In ,argininevasopressin resistance, the increase in urine osmolality can be up to 45%, but overall these numbers are much lower than those that occur in partial argininevasopressin deficiency (usually < 300 mOsm/kg [300 mmol/kg]).
In psychogenic polydipsia, urine osmolality is < 100 mOsm/kg (100 mmol/kg). Decreasing water intake gradually will lead to decreasing urine output, increasing plasma and urine osmolality and serum sodium concentration.
Measurement of circulating ADH is the most direct method of diagnosing argininevasopressinargininevasopressin deficiency and appropriately elevated in argininevasopressin resistance. However, ADH levels are not routinely available. In addition, water deprivation is so accurate that direct measurement of ADH is rarely necessary. If measured, ADH levels should be checked at the beginning of the water deprivation test, when the patient is well hydrated; ADH levels should increase as intravascular volume decreases.
Treatment of Polyuria
Key Points
Use of diuretics and uncontrolled diabetes mellitus are common causes of polyuria.
In the absence of diabetes mellitus and diuretic use, the most common causes of chronic polyuria are primary polydipsia, argininevasopressin deficiency, and argininevasopressin resistance.
Hypernatremia can indicate argininevasopressin deficiency or argininevasopressin resistance.
Hyponatremia is more characteristic of polydipsia.
Abrupt onset of polyuria suggests argininevasopressin deficiency.
A water deprivation test can help with diagnosis but should only be done with the patient under close supervision.
