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Polyuria

By

Geetha Maddukuri

, MD, Saint Louis University

Reviewed/Revised Dec 2022
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Topic Resources

Polyuria is urine output of > 3 L/day; it must be distinguished from urinary frequency Urinary Frequency Urinary frequency is the need to urinate many times during the day, at night (nocturia), or both but in normal or less-than-normal volumes. Frequency may be accompanied by a sensation of an... read more , 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 argininevasopressin) 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 Renal Glucosuria Renal glucosuria is glucose in the urine without hyperglycemia; it results from either an acquired or an inherited, isolated defect in glucose transport or occurs with other renal tubule disorders... read more 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 one 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 Some Causes of Polyuria Some Causes of Polyuria ) in adults and children is

In the absence of diabetes mellitus, the most common causes are

Table

Evaluation of Polyuria

History

History of present illness should include the amounts of fluid consumed and voided to distinguish between polyuria Polyuria 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... read more and urinary frequency Urinary Frequency Urinary frequency is the need to urinate many times during the day, at night (nocturia), or both but in normal or less-than-normal volumes. Frequency may be accompanied by a sensation of an... read more . 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.

Past medical history should be reviewed for conditions associated with polyuria, including diabetes mellitus Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more , psychiatric disorders, sickle cell disease Sickle Cell Disease Sickle cell disease (a hemoglobinopathy) causes a chronic hemolytic anemia occurring almost exclusively in people with African ancestry. It is caused by homozygous inheritance of genes for hemoglobin... read more Sickle Cell Disease , sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more Sarcoidosis , amyloidosis Amyloidosis Amyloidosis is any of a group of disparate conditions characterized by extracellular deposition of insoluble fibrils composed of misaggregated proteins. These proteins may accumulate locally... read more Amyloidosis , and hyperparathyroidism Hypercalcemia Hypercalcemia is a total serum calcium concentration > 10.4 mg/dL (> 2.60 mmol/L) or ionized serum calcium > 5.2 mg/dL (> 1.30 mmol/L). Principal causes include hyperparathyroidism... read more . A family history of polyuria and excessive water drinking should be noted. Drug history should note use of any drugs associated with nephrogenic diabetes insipidus Nephrogenic Diabetes Insipidus Nephrogenic diabetes insipidus (NDI) is an inability to concentrate urine due to impaired renal tubule response to vasopressin (ADH), which leads to excretion of large amounts of dilute urine... read more (see table Some Causes of Polyuria Some Causes of Polyuria 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 Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more ) 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 Sjögren Syndrome Sjögren syndrome is a relatively common chronic, autoimmune, systemic, inflammatory disorder of unknown cause. It is characterized by dryness of the mouth, eyes, and other mucous membranes ... read more 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 Some Causes of Polyuria Some Causes of Polyuria ), but testing is usually necessary. Diabetes insipidus ArginineVasopressin Deficiency (Central Diabetes Insipidus) Arginine vasopressin deficiency (central diabetes insipidus) results from a deficiency of vasopressin (antidiuretic hormone [ADH]) due to a hypothalamic-pituitary disorder. Polyuria and polydipsia... read more is suggested by a history of cancer or chronic granulomatous disease (due to hypercalcemia Hypercalcemia Hypercalcemia is a total serum calcium concentration > 10.4 mg/dL (> 2.60 mmol/L) or ionized serum calcium > 5.2 mg/dL (> 1.30 mmol/L). Principal causes include hyperparathyroidism... read more ), use of certain drugs (lithium, cidofovir, foscarnet, ifosfamide), and less common conditions (eg, sickle cell disease Sickle Cell Disease Sickle cell disease (a hemoglobinopathy) causes a chronic hemolytic anemia occurring almost exclusively in people with African ancestry. It is caused by homozygous inheritance of genes for hemoglobin... read more Sickle Cell Disease , renal amyloidosis Amyloidosis Amyloidosis is any of a group of disparate conditions characterized by extracellular deposition of insoluble fibrils composed of misaggregated proteins. These proteins may accumulate locally... read more Amyloidosis , sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more Sarcoidosis , Sjögren syndrome Sjögren Syndrome Sjögren syndrome is a relatively common chronic, autoimmune, systemic, inflammatory disorder of unknown cause. It is characterized by dryness of the mouth, eyes, and other mucous membranes ... read more Sjögren Syndrome ) that have manifestations that are often more prominent than and precede the polyuria.

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

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 Orthostatic Hypotension Orthostatic (postural) hypotension is an excessive fall in blood pressure (BP) when an upright position is assumed. The consensus definition is a drop of > 20 mm Hg systolic, > 10 mm Hg... read more and postural tachycardia appear, 5% of the initial body weight has been lost, or the urinary concentration does not increase > 30 mOsm/kg (30 mmol/kg) in sequentially voided specimens. Serum electrolytes and osmolality are again determined, and 5 units of aqueous vasopressin are injected subcutaneously. Urine for osmolality measurement is collected one final time 60 minutes postinjection, and the test is terminated.

A normal response produces maximum urine osmolality after dehydration (> 700 mOsm/kg [700 mmol/kg]), and osmolality does not increase more than an additional 5% after injection of vasopressin.

In central diabetes insipidus ArginineVasopressin Deficiency (Central Diabetes Insipidus) Arginine vasopressin deficiency (central diabetes insipidus) results from a deficiency of vasopressin (antidiuretic hormone [ADH]) due to a hypothalamic-pituitary disorder. Polyuria and polydipsia... read more , patients are typically unable to concentrate urine to greater than the plasma osmolality but are able to increase their urine osmolality after vasopressin administration. The increase in urine osmolality is 50 to 100% in central diabetes insipidus vs 15 to 45% with partial central diabetes insipidus.

In nephrogenic diabetes insipidus Nephrogenic Diabetes Insipidus Nephrogenic diabetes insipidus (NDI) is an inability to concentrate urine due to impaired renal tubule response to vasopressin (ADH), which leads to excretion of large amounts of dilute urine... read more , patients are unable to concentrate urine to greater than the plasma osmolality and show no additional response to vasopressin administration. Occasionally in partial nephrogenic diabetes insipidus, the increase in urine osmolality can be up to 45%, but overall these numbers are much lower than those that occur in partial central diabetes insipidus (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 central diabetes insipidus. Levels at the end of the water deprivation test (before the vasopressin injection) are low in central diabetes insipidus and appropriately elevated in nephrogenic diabetes insipidus. 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

Treatment varies by cause. Troubling nocturia can be managed by measures such as reducing fluid intake before bedtime, the use of desmopressin, and/or improving sleep hygiene.

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, central diabetes insipidus, and nephrogenic diabetes insipidus.

  • Hypernatremia can indicate central or nephrogenic diabetes insipidus.

  • Hyponatremia is more characteristic of polydipsia.

  • Abrupt onset of polyuria suggests central diabetes insipidus.

  • A water deprivation test can help with diagnosis but should only be done with the patient under close supervision.

Drugs Mentioned In This Article

Drug Name Select Trade
Eskalith, Eskalith CR, Lithobid
Vistide
Foscavir
Ifex
Pitressin, Vasostrict
DDAVP, Minirin, Nocdurna, Noctiva, Stimate
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NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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