Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.
Distinguish renal vasopressin resistance from other polyuria, protect against hypernatraemic dehydration, and manage acquired or inherited disease with specialist safeguards.
Arginine vasopressin binds the V2 receptor on collecting-duct principal cells, increasing apical aquaporin-2 water channels and permitting concentration of urine. AVPR2 dysfunction, AQP2 dysfunction or acquired disruption of this pathway prevents the kidney responding appropriately. Large volumes of dilute urine produce thirst, nocturia and sleep disruption. Sodium concentration reflects the balance between water loss and replacement, so a normal sodium in a freely drinking patient does not exclude substantial nephrogenic disease.
Lithium is the leading acquired medicine cause. It enters principal cells partly through epithelial sodium channels and can reduce aquaporin expression and cause chronic structural injury. The clinical response to polyuria must balance renal harm with the psychiatric benefit of lithium; patients should not stop it themselves. Hypercalcaemia and sustained hypokalaemia reduce concentrating ability, while obstruction and chronic interstitial disease can create partial resistance. Congenital AVPR2 disease is usually X-linked and often severe in boys; AQP2 disease may be recessive or dominant and affects either sex.
Lithium, hypercalcaemia, sustained hypokalaemia, urinary obstruction and chronic tubulointerstitial disease can reduce collecting-duct responsiveness to arginine vasopressin.
Pathogenic AVPR2 variants, commonly X-linked, or AQP2 variants impair receptor signalling or collecting-duct water-channel function and may present in infancy.
Rising plasma tonicity appropriately stimulates thirst and arginine vasopressin secretion, distinguishing the core defect from absent central hormone production.
V2-receptor signalling or aquaporin-2 availability is reduced, so principal cells cannot increase water permeability adequately in response to circulating hormone.
Water remains within the tubular lumen and large volumes of dilute urine are excreted despite an intact physiological drive to conserve water.
Thirst and drinking may preserve sodium until illness, fasting, dependency or impaired cognition interrupts access, when hypernatraemia and hypovolaemia develop quickly.
Persistent large-volume pale urine, thirst and nocturia with low urine osmolality point to impaired water conservation rather than simple urinary frequency.
Dry mucosae, hypotension, tachycardia, lethargy, irritability, confusion or seizure after reduced water access signals dangerous uncompensated loss.
Polyuria and polydipsia during long-term lithium therapy may be nephrogenic DI, but hyperglycaemia, hypercalcaemia, CKD and lithium toxicity still need assessment.
An infant with relentless thirst, fever, vomiting, constipation, poor growth and recurrent hypernatraemia may have inherited AVPR2 or AQP2 disease.
Moderately dilute urine and some desmopressin response can occur, so binary interpretation without baseline osmolality and supervised protocol is unreliable.
Excess water intake suppresses vasopressin and dilutes urine; supervised dynamic testing and baseline plasma tonicity distinguish this from renal hormone resistance.
Insufficient hormone secretion causes similarly dilute polyuria but usually shows a stronger concentrating response to desmopressin during specialist testing.
Glucose, urea, mannitol or diuretics increase solute excretion and usually produce a less dilute urine than a pure water diuresis.
Cystitis, overactive bladder and outlet obstruction cause frequent small voids; a measured daily volume separates these from true excess water excretion.
Unreplaced free-water loss raises plasma tonicity, causing lethargy, irritability, confusion, seizures and potentially permanent neurological harm.
Severe polyuria can reduce circulating volume, causing hypotension, renal hypoperfusion and acute kidney injury that further complicates medicine handling.
Dehydration and falling filtration can raise lithium exposure, worsening neurological toxicity and tubular dysfunction unless medicine and fluid status are reviewed together.
Congenital disease can cause poor growth and recurrent childhood illness, while chronic thirst, nocturia and sleep disruption substantially impair adult daily life.
An alert patient with intact thirst may replace enormous renal water losses and keep sodium normal until access is interrupted.
Cystitis, overactive bladder and obstruction cause frequent small voids, whereas DI requires genuinely increased daily water volume.
The renal diagnosis does not by itself determine cessation; psychiatric history, alternatives, toxicity and reversibility all shape the plan.
The same medicine that lowers urine volume can reduce lithium clearance and provoke toxicity unless dosing and levels are actively coordinated.
A person unable to concentrate urine may become rapidly hypernatraemic, making protocol-led supervision and stopping criteria essential.
Diagnosing DI from urinary frequency without confirming a high 24-hour volume and dilute urine.
Reassuring from a normal sodium when the patient is drinking continuously to compensate for severe renal losses.
Performing an unsupervised water-deprivation test at home or on a ward without defined monitoring and stopping criteria.
Stopping lithium abruptly without mental-health input or failing to check for interacting medicines and toxicity.
Prescribing a thiazide to a lithium user without anticipating a rise in lithium concentration.
Using chronic NSAIDs casually in a patient already vulnerable to dehydration and kidney injury.
Assuming desmopressin treats all forms of diabetes insipidus and overlooking renal resistance.
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An adult with 7 litres of dilute urine daily and plasma sodium 148 mmol/L is suspected of nephrogenic diabetes insipidus. What is the safest next diagnostic approach?
National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.
Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem · Content changes
May cause hyponatraemia, hypokalaemia, gout, hypotension and AKI. In a lithium user it can raise lithium concentration markedly, requiring prescriber-led adjustment and frequent levels.
Can cause dangerous hyperkalaemia, especially with CKD, ACE inhibitors, ARBs or potassium supplements; fixed-dose combinations and renal thresholds require review.
Excess fluid intake during treatment can cause dilutional hyponatraemia, seizure or cerebral oedema. Diagnostic administration must be supervised and interpreted with urine osmolality.
AKI, papillary injury, sodium retention, hypertension, gastrointestinal bleeding and cardiovascular events are important, particularly in CKD or dehydration.