Polyuria

Essentials

• Establish whether the patient has true polyuria with excessive amounts of dilute urine, or does he/she have increased urinary frequency with the amount and concentration of the urine excreted being normal.

Definition

• Polyuria is a condition characterized by excessive excretion of urine in a 24 hour period. The condition is regarded as polyuria when the urine amount exceeds 50 ml/kg/day, i.e. in a 70-kg person > 3.5 l/day.
• Polyuria can be further divided into two categories.
  • Water diuresis (low urine osmolality, i.e. < 300 mosm/kg H₂O)
  • Osmotic diuresis (usually elevated urine osmolality)

Aetiology

• The most common cause of osmotic diuresis is glycosuria associated with hyperglycaemia. More rare aetiological factors include increased urea concentration following parenteral or enteral feeding, administration of mannitol or following a contrast medium investigation (transient).
• Water diuresis can be further divided into two types.
  • Primary polydipsia (plasma sodium and serum osmolality normal or low)
  • Diabetes insipidus (plasma sodium and serum osmolality normal or high); NB. the new naming practice of the disease.
    • Pituitary: inadequate ADH (antidiuretic hormone) i.e. arginine vasopressin secretion; the new name is arginine vasopressin deficiency (AVP-D)
    • Gestational
    • Nephrogenic: inadequate effect of ADH; the new name is arginine vasopressin resistance (AVP-R)
• Primary polydipsia
  • Excessive fluid intake will lead to the accumulation of fluid in the body, to lowered plasma osmolality and to the prevention of ADH secretion. This will result in large amounts of dilute urine. A healthy individual is able to consume up to 20 litres of fluid in 24 hours without adverse effects. However, if ADH secretion increases either for physiological reasons (e.g. nausea) or through medication, water intoxication may ensue.
  • Primary polydipsia is further divided into psychogenic and dipsogenic subtypes.
    • In psychogenic polydipsia the consumption of large amounts of water is either due to the perceived health benefits gained or compulsive desire to drink (schizophrenia; note that ADH secretion may be abnormal in schizophrenia).
    • In dipsogenic polydipsia the patient has a dysfunction of the thirst centre which becomes stimulated even though plasma osmolality remains normal. The cause may originate from medication, a central nervous system illness or be unknown.
• Aetiology of diabetes insipidus
  • Pituitary (AVP-D): idiopathic, hereditary, head injury, autoimmune, brain tumour, infection, pituitary surgery, compression by an aneurysm
  • Nephrogenic (AVP-R): medication (particularly lithium), hypokalaemia and hypercalcaemia Hypercalcaemia and Hyperparathyroidism (easily reversible), toxins (ethanol, ethylene glycol), pyelonephritis and many tubulo-interstitial renal diseases, congenital forms.
  • Gestational AVP-D: in some cases a history of previous, undiagnosed mild diabetes insipidus of pituitary origin. The placenta degrades endogenic ADH, but not synthetic desmopressin. Will reverse after delivery.

Diagnosis and treatment

1. Patient history is central. There may be several background factors for the large urine amounts. Try to distinguish between polyuria and increased urinary frequency. A urinary diary may be of help in the investigation. Keep the definition of polyuria in mind.
   • The duration of the problem? The onset is usually acute in pituitary aetiology.
   • Does the amount of urine vary from day to day?
   • At what time of the day is the problem worst? Particularly nocturnal micturition (nocturia) is an early sign of polyuria.
   • How many episodes of micturition during the day and night?
   • Does reducing fluid intake affect the amount of urine?
   • Problems with continence?
   • Pain or discomfort during micturition?
   • Aggravating factors?
   • Colour of the urine?
   • Nocturnal enuresis?
   • Medication (diuretics in particular)?
   • History of urinary tract infections?
   • Lifestyle; fluid intake per 24 hours? Coffee, alcohol, dietary salt intake?
   • Drinking and urinating diary is a helpful tool
2. Basic investigations
   • Plasma creatinine, potassium, sodium, calcium, glucose (diabetes mellitus). It is recommended to determine the 24-hour value of urinary calcium and potassium (urine collection over 24 hours), particularly if the amount of urine cannot otherwise be clarified.
   • Urinalysis: no abnormal findings in polyuria caused by water diuresis
   • In men, PSA (remember to palpate the prostate)
3. If history and basic investigations are still suggestive of polyuria, proceed as follows.
   • Following overnight fluid deprivation (if possible) measure plasma sodium, and both plasma and early morning urine osmolality, as well as plasma copeptin.
     • If plasma osmolality (plasma sodium) is normal and early morning urine osmolality > 800 mosm/kg H₂O, renal concentration of urine is normal and the patient has no significant problems of water metabolism.
     • Low plasma osmolality (sodium) in a polyuric patient is suggestive of primary polydipsia. Basic investigations are, however, often normal.
     • If plasma osmolality > 295 mosm/kg H₂O or plasma sodium > 144 mmol/l and urine osmolality < 300 mosm/kg H₂O, diabetes insipidus (AVP-D/AVP-R) can usually be diagnosed. In partial diabetes insipidus it is not possible to make differential diagnosis based on basic investigations.
4. Further investigations and initiation of treatment is carried out by a specialist team (endocrinology or nephrology). Further investigations may include:
   • Differential diagnosis; is the condition of pituitary or nephrogenic origin? Determine plasma copeptin (secreted from neurohypophysis in equimolar amounts with ADH) and response to desmopressin (urine not concentrated in nephrogenic causes). Plasma copeptin concentration is low if the condition is of pituitary origin and increased if it is of nephrogenic origin (when interpreting the results one has to make sure that the stimulus is sufficient, i.e. that plasma osmolality is increased).
   • To diagnose partial AVP-D/AVP-R i.e. diabetes insipidus, water deprivation test combined with hypertonic saline infusion test can be carried out. The test is performed in an endocrinology unit and its interpretation requires experience.
   • In pituitary diabetes insipidus, MRI of the head
   • Diagnosis and treatment of renal disease (nephrology)
   • Identification of some other aetiological factor (e.g. lithium medication)
   • Treatment is aimed at the causative factor. Lack of ADH is treated with synthetic arginine vasopressin.