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Practice Rational testing

Investigating polyuria

BMJ 2013; 347 doi: https://doi.org/10.1136/bmj.f6772 (Published 02 December 2013) Cite this as: BMJ 2013;347:f6772
  1. Adam D Jakes, academic foundation doctor1,
  2. Sunil Bhandari, consultant nephrologist/honorary clinical professor2
  1. 1Leeds Teaching Hospitals NHS Trust, Beckett Street, Leeds LS9 7TF, UK
  2. 2Renal Unit, Hull and East Yorkshire Hospitals NHS Trust and Hull York Medical School, Kingston upon Hull HU3 2JZ, UK
  1. Correspondence to: S Bhandari Sunil.bhandari{at}hey.nhs.uk
  • Accepted 3 October 2013

Polyuria represents a common presentation in primary care that can often be a diagnostic challenge requiring careful consideration. This article provides a structured, logical approach for investigating polyuria, highlights the importance and relevance of various tests, and advises on when to refer to a specialist

A 43 year old male teacher presented to his general practitioner with frequent urination and polydipsia for six weeks. He was passing large volumes of urine throughout the day and night, but he denied dysuria, hesitancy, or urgency. His fluid intake was approximately two litres a day and included two cups of tea. He had no relevant medical history; reported no weight loss, visual changes, or bowel disturbance; and took no drugs, including over the counter drugs or herbal remedies. There was no family history of diabetes or renal disease. Clinical examination was unremarkable, and his blood pressure was 138/84 mm Hg.

What is the next investigation?

Clinical history

A thorough clinical history is essential to distinguish between polyuria and urinary frequency (box 1). Urine volume can be difficult for patients to quantify, and use of fluid charts (measuring fluid input and output) may be helpful. The presence of urinary symptoms should be established, along with the timing of urination (nocturnal, throughout the day, or both). This may help clinicians to distinguish between possible causes by the relation to tubular disorders versus anatomical abnormalities, such as overactive bladder syndrome in which frequency and urgency of urination are present rather than polyuria or prostatic disease.

Box 1 Glossary of terms

  • Polyuria—The production of “abnormally” large volumes of urine (>3 L/day in adults)

  • Urinary frequency—The excessive need to urinate, which is not normal for the patient. The total volume of urine passed is within normal limits

  • Polydipsia—Excessive thirst as a symptom of disease or psychological disturbance (resulting consumption of >3 L/day)

  • Nocturia—The need to wake from sleep and pass urine (urinating once a night is presumed to be within normal limits)

  • Osmolarity—The measurement of a solute concentration affected by water content, temperature, and ambient pressure. It can be calculated, using laboratory derived data, as [2Na+]+[2K+]+[glucose]+[urea] (mmol/L)

  • Osmolality—The measurement of a solute concentration that is independent of temperature and pressure. This laboratory measurement is presented as the number of moles of solute per litre (mmol/kg)

Polyuria and polydipsia are regularly experienced together and share similar causes. Box 2 lists the population prevalence of diseases that can cause polyuria. Diabetes mellitus affects more than 1 in 20 people in the United Kingdom and is the most common cause of polyuria in both children and adults.1 Diabetes should be suspected, particularly if the patient has an associated history of weight loss (type 1 diabetes) or a family history of diabetes (type 2 diabetes). Patients with heart failure may experience nocturia owing to fluid accumulating as pedal oedema and returning to the blood stream when the patient lies flat. Older patients with hypertension may also have nocturnal polyuria, as a result of the effects of hypertension on cardiovascular and renal physiology.2 Moderate to severe chronic kidney disease has a prevalence of 0.2% in the general population and can occasionally give rise to either polyuria or nocturia.3 Therefore, check for visible or microscopic haematuria and systemic causes of renal disease (arthralgia, rashes, and constitutional symptoms), as anecdotal evidence suggests that patients with vasculitis and systemic lupus erythematosus may occasionally present with polyuria.

Box 2 The population prevalence of diseases causing polyuria

Common (>1 in 10)
  • Diuretics/caffeine/alcohol*

  • Diabetes mellitus1

  • Lithium8

  • Heart failure*

Infrequent (1 in 100)
  • Hypercalcaemia6

  • Hyperthyroidism9

Rare (1 in 1000)
  • Chronic renal failure3

  • Primary polydipsia*

  • Hypokalaemia*

Very rare (<1 in 10 000)
  • Diabetes insipidus7

  • *Prevalence unknown but categorised approximately

A full drug history is essential to rule out a potential pharmacological cause. Ask particularly about substances that increase urine output (diuretics, lithium, alcohol, and caffeine), as well as over the counter drugs. Excess vitamin D supplements may lead to hypercalcaemia, which may in turn cause polyuria and polydipsia.4 However, primary hyperparathyroidism and malignancy account for 90% of patients with hypercalcaemia.5 Malignancy is present in 1.1-3.9% of the general population, and hypercalcaemia develops in up to 30% of patients with cancer.6

Diabetes insipidus results in the excretion of large amounts of dilute urine and can be subdivided into central or nephrogenic types. It is very rare, with an incidence of 3 in 100 000 in the general population.7 Central diabetes insipidus is characterised by a lack of antidiuretic hormone (also known as vasopressin) production caused by infiltration of or damage to the pituitary as a result of a tumour, a head injury, neurosurgery, haemochromatosis, or sarcoidosis. Nephrogenic diabetes insipidus occurs when the kidneys become insensitive to the effects of antidiuretic hormone, often because of acquired kidney disorders or therapeutic lithium use. Up to 40% of patients taking lithium develop nephrogenic diabetes insipidus.8 Hyperthyroidism is a common endocrine disorder found in 1.3% of the general population.9 Elicit symptoms of thyrotoxicosis (sweating, heat intolerance), as this stimulates thirst and causes an increase in circulating natriuretic peptides, resulting in greater excretion of both sodium and water and hence leading to symptoms of polyuria.10

Determine the patient’s daily fluid intake to assess whether it is in excess. This can be done by using a simple fluid chart that monitors fluid intake and urine output through the day. Primary polydipsia is the excessive intake of fluid, in the absence of a physiological stimulus to drink, caused by a mental disorder or disordered thirst. It is common among institutionalised psychiatric patients (6-20%)11; the prevalence in the general population is unknown, but it is thought to be rare. Polyuria throughout the night is uncommon in this condition. Primary polydipsia is difficult to treat in the community and, owing to the risk of hypotonic hyponatraemia, may require admission to hospital.11

Clinical examination

Note the patient’s blood pressure, general appearance, and signs of dehydration (skin turgor, capillary refill, and mucous membranes). The presence of weight loss may support causes such as diabetes or thyroid disease, whereas muscle weakness may be a manifestation of metabolic derangements. Clinical examination rarely elicits positive findings; however, it is important to exclude a bitemporal hemianopia, which may be a sign of a tumour causing compression and leading to central diabetes insipidus. If a central cause is suspected, referral to secondary care is indicated for further investigation including magnetic resonance imaging of the brain and measurement of pituitary hormones. Palpate the abdomen for masses, particularly an enlarged kidney, which would warrant an ultrasound scan to rule out hydronephrosis and urinary tract abnormalities. Finally polyuria can occur after paroxysmal tachycardias including atrial flutter and fibrillation.12

The history and elicited clinical findings should then direct appropriate investigations and referral. Box 3 lists the basic investigations likely to lead to a diagnosis; these are discussed below.

Box 3 Summary of investigations

Primary care
  • Home fluid balance chart

  • Urine dipstick

  • Capillary blood glucose

  • Serum urea and electrolytes, calcium

  • Random/fasting glucose or glycated haemoglobin (HbA1c)

  • Urine and plasma osmolality

  • Urine electrolytes

Secondary care (endocrinology)
  • Water deprivation test*

  • Desmopressin administration

  • Measurement of plasma antidiuretic hormone

  • Anterior pituitary hormones†

  • Magnetic resonance scan of brain/pituitary

  • *Urine and plasma osmolalities are measured in response to fluid deprivation and subsequent administration of desmopressin (antidiuretic hormone)

  • †Thyroid stimulating hormone, prolactin, luteinising hormone, follicle stimulating hormone, growth hormone, adrenocorticotrophic hormone

Urinalysis: urine dipstick

The presence of glycosuria necessitates a fasting or random glucose blood test or HbA1c measurement to rule out diabetes. The renal threshold for glucose may be lower in children and pregnant women, as well as in renal glycosuria when even normal blood glucose concentrations produce a positive dipstick. A venous blood glucose concentration can help to identify these patients and aid further investigation and treatment.

The presence of leucocytes or nitrites in conjunction with urinary symptoms should direct the clinician towards a diagnosis of a urinary tract infection. Specific symptoms such as dysuria and frequency (without vaginal discharge or irritation in women) raise the probability of a urinary tract infection to more than 90%.13 The combined presence of leucocytes and nitrites on urine dip, together with clinical symptoms, has a sensitivity of 68-88% with a negative predictive value of 84-98%.14 Most studies have concluded that a negative urine dipstick without specific urinary symptoms is sufficient to rule out a diagnosis of a urinary tract infection.13 14

The specific gravity of the urine gives an estimate of its concentration and thus an indication of its osmolality. A high or low specific gravity (normal: 1.010-1.025) should prompt evaluation of osmolality to assist diagnosis. Twenty four hour urine collection, although useful in quantifying a patient’s urine output, is not practical in the community and is best reserved for secondary care.

Urine/plasma osmolality with urine electrolytes

Osmolality is monitored by osmoreceptors in the hypothalamus, which detect very small changes and control release of antidiuretic hormone accordingly. Antidiuretic hormone acts on the collecting ducts to increase reabsorption of water (figure). If antidiuretic hormone production is lacking or the kidney has become insensitive to it, such as in diabetes insipidus, the urine osmolality will be low but the plasma osmolality will be high. In primary polydipsia, urine osmolality will be low, with plasma osmolality found to be normal or low.

Figure1

Mechanism of antidiuretic hormone (ADH) and feedback loop. ADH is controlled by hypothalamus in response to changes in osmolality of blood. Hence rise in plasma osmolality leads to increase in ADH, and fall in osmolality leads to decrease in ADH secretion.15 Low specific gravity (<1.010) should prompt further investigation into osmolality of patient’s urine. *Of collecting ducts, increasing water reabsorption

Blood tests

Capillary blood glucose, plasma glucose, and HbA1c—Capillary blood glucose is a quick and easy screening test that can help to determine whether a fasting plasma glucose/HbA1c is needed. A diagnosis of diabetes mellitus can be made if the patient has a typical history (polyuria, polydipsia, weight loss), along with a random glucose or two hour glucose tolerance test above 11.1 mmol/L, or a fasting plasma glucose above 7.0 mmol/L. An HbA1c of 48 mmol/mol or above (or >6.5%) may also be used for diagnosis of diabetes, if no conditions precluding its use (for example, in children, steroid use) are present. Diabetes mellitus can be largely excluded as a cause of polyuria if the fasting plasma glucose is within the normal range; however, this is not true for a normal HbA1c.16

Serum urea, creatinine, and electrolytes (including calcium)—These simple tests enable assessment of kidney function and may aid diagnosis. Hypernatraemia is a good marker of true water depletion,17 whereas hypokalaemia, a common electrolyte disturbance, is an uncommon cause of polyuria. Calcium abnormalities may warrant parathyroid hormone, phosphate, and alkaline phosphatase measurements to explore underlying causes.

Thyroid function tests—Thyrotoxicosis can occasionally cause polyuria, as previously described.

Outcome

A urine dipstick was negative with a low specific gravity (<1.005). The absence of urinary symptoms made a urinary tract infection unlikely. The patient’s kidney function, calcium, and potassium were normal. Advice from a renal physician recommended checking the urine and plasma osmolality. Plasma osmolality was high (318 mmol/kg; normal 280-295 mmol/kg), and urine osmolality was low (150 mmol/kg; normal 300-900 mmol/kg), indicating a problem with the patient’s ability to concentrate urine. He was referred to secondary care. A water deprivation test had no effect on the urine osmolality, which remained low, excluding primary polydipsia. Subsequent administration of desmopressin (an antidiuretic hormone analogue) led to an increase in the urine osmolality. The measured antidiuretic hormone concentration was low, confirming diabetes insipidus. Computed tomography and magnetic resonance scans of the head, pituitary hormone concentrations, and autoantibody screening (arginine vasopressin antibodies) were negative. The patient was diagnosed as having idiopathic central diabetes insipidus, which accounts for about 30% of cases of diabetes insipidus. He was treated with 10 µg of nasal desmopressin daily, which improved his symptoms and normalised his biochemistry. His sodium and plasma osmolality were monitored to ensure that adequate fluid homeostasis was maintained.

Learning points

  • In patients with increased urination, take a thorough clinical history to determine whether it is urinary frequency or polyuria; a home fluid balance chart may help to make the distinction

  • Exclude use of drugs (for example, caffeine, alcohol, diuretics, and lithium) and diabetes mellitus in all patients with polyuria

  • Urine dipstick testing is useful, and specific gravity can direct further investigations/referral

  • Plasma/urine osmolality may help to distinguish between different diagnoses

Notes

Cite this as: BMJ 2013;347:f6772

Footnotes

  • This series of occasional articles provides an update on the best use of key diagnostic tests in the initial investigation of common or important clinical presentations. The series advisers are Steve Atkin, professor, head of department of academic endocrinology, diabetes, and metabolism, Hull York Medical School; and Eric Kilpatrick, honorary professor, department of clinical biochemistry, Hull Royal Infirmary, Hull York Medical School. To suggest a topic for this series, please email us at practice{at}bmj.com

  • Contributors: All the authors have contributed according to ICMJE guidelines. ADJ contributed to planning, drafting, and revising the article and to approval of the final version. SB had the idea for the article; contributed to planning, drafting, and revising the article; and approved the final version. SB is guarantor for the overall content. Stephen Atkin, Stephen Orme, and David Pearson reviewed the article and gave advice on its content.

  • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance: Not commissioned; externally peer reviewed.

  • Patient consent not required (patient anonymised, dead, or hypothetical).

References

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