Synopsis
Distinguish renal vasopressin resistance from other polyuria, protect against hypernatraemic dehydration, and manage acquired or inherited disease with specialist safeguards.
- Nephrogenic diabetes insipidus is renal resistance to arginine vasopressin, now also termed AVP resistance, causing hypotonic polyuria despite an intact thirst and hormone response.
- Confirm true polyuria by measured volume rather than urinary frequency; in adults a 24-hour output above about 3 litres is a useful threshold but size and intake matter.
- Exclude osmotic diuresis from glucose, urea, mannitol or diuretics and primary polydipsia before undertaking specialised water-balance testing.
- Acquired causes include lithium, hypercalcaemia, hypokalaemia, obstruction and tubulointerstitial disease; congenital disease most often involves X-linked AVPR2 or AQP2 variants.
- People with intact thirst and unrestricted water can maintain sodium, but illness, fasting, impaired cognition, dependence or restricted access can reveal life-threatening dehydration quickly.
- Paired plasma sodium or osmolality and urine osmolality show whether urine is inappropriately dilute; water-deprivation testing must be supervised by an experienced endocrine or renal service.
- Desmopressin usually has little effect in complete nephrogenic disease, unlike central AVP deficiency, although partial responses and mixed states require specialist interpretation.
- Treat the cause, guarantee water access, reduce dietary solute with dietetic advice and consider thiazide or amiloride under specialists; chronic NSAID therapy is not routine because renal and gastrointestinal harms can outweigh benefit.
Key red flags
Dry mucosae, hypotension, tachycardia, lethargy, irritability, confusion or seizure after reduced water access signals dangerous uncompensated loss.
An infant with relentless thirst, fever, vomiting, constipation, poor growth and recurrent hypernatraemia may have inherited AVPR2 or AQP2 disease.
Investigation priorities
Confirm polyuria and quantify ongoing water loss.
Management branches
A patient reports frequent urination and excessive thirst.
- Distinguish urinary frequency from high volume using a bladder history, fluid chart or complete 24-hour urine measurement.
- Pair urine osmolality with plasma sodium or osmolality and screen glucose, calcium, potassium, renal function and diuretic or SGLT2 use.
- If hypotonic polyuria persists, refer for supervised endocrine or renal testing rather than advising home water restriction.
Key medicines
Thiazide-type diureticSelect a locally available agent and low starting dose only under renal or endocrine advice, then titrate against measured urine volume, blood pressure and electrolytes.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.
AmilorideUse specialist-selected dosing from the current formulary, particularly in lithium-associated disease, with early and repeated potassium, creatinine and lithium checks.Can cause dangerous hyperkalaemia, especially with CKD, ACE inhibitors, ARBs or potassium supplements; fixed-dose combinations and renal thresholds require review.