Causes in UK practice
ACQUIRED — by far the commonest:
- LITHIUM — develops in up to 30-50% of long-term users; partly reversible if stopped early, may be irreversible after years
- Hypercalcaemia (corrected calcium >2.75 mmol/L) — reverses with normocalcaemia
- Hypokalaemia (<3.0 mmol/L sustained)
- Post-obstructive diuresis
- Sickle cell disease / trait
- Chronic interstitial nephritis (analgesic, Sjögren's, sarcoidosis)
- Drugs: demeclocycline, amphotericin B, foscarnet, ifosfamide, cidofovir, ofloxacin, rifampicin, vaptans
- Post-AKI recovery (transient)
Inherited
- AVPR2 (X-linked recessive) — vasopressin V2 receptor mutation; presents in male infants with failure to thrive, dehydration, hypernatraemic seizures
- AQP2 (autosomal recessive or dominant) — aquaporin-2 water channel mutation
- Female carriers of AVPR2 mutations may have mild symptoms
Pregnancy
- Gestational DI in third trimester from placental vasopressinase
- Responds to desmopressin (which is vasopressinase-resistant)
- Resolves postpartum
Clinical features and assessment
Symptoms
- Polyuria — often >3-5 L/day (and up to 20 L in severe inherited cases)
- Nocturia, enuresis in children
- Polydipsia — preference for cold water
- Hypernatraemia: confusion, lethargy, seizures, especially in elderly, children or anyone with restricted water access
- Failure to thrive in infants with congenital NDI
- Hydronephrosis from chronic high urine flow (especially congenital)
Initial Tests
- Paired serum + urine osmolality (urine osmolality <300 mOsm/kg with serum >295 mOsm/kg is suggestive)
- Serum sodium, potassium, calcium, glucose, urea, creatinine
- Urine glucose (exclude osmotic diuresis from diabetes mellitus)
- Drug history (lithium levels, duration)
- 24h urine volume
WATER DEPRIVATION TEST (in a controlled setting — never at home):
- Patient deprived of water under medical supervision
- Cranial DI: urine stays dilute, concentrates after desmopressin
- Nephrogenic DI: urine stays dilute, no response to desmopressin
- Primary polydipsia: urine concentrates with water deprivation alone
- Now often replaced by copeptin testing where available (more accurate)
Imaging
- Ultrasound for hydronephrosis or megacystis (especially congenital)
- MRI pituitary if cranial DI considered
Kidney Vitality is a daily multivitamin developed by a UK Consultant Nephrologist using renal nutrition principles. It contains no added potassium, magnesium, phosphorus or iron, and no herbal blends. See the formulation.
Treatment
Treat The Underlying Cause
- Stop or substitute lithium (with psychiatry — valproate, lamotrigine, antipsychotics may be alternatives)
- Correct hypercalcaemia (treat underlying cause: vitamin D toxicity, primary hyperparathyroidism, malignancy)
- Correct hypokalaemia (potassium supplementation; treat cause)
- Treat obstruction
Fluid
- Free access to water — critical; never restrict
- Beware admissions, surgery, dementia, intubation — sodium can climb rapidly
- During acute hypernatraemia: replace water deficit slowly (correct serum Na no faster than 10-12 mmol/L per 24h)
Diet
- Low-salt, low-protein diet reduces solute load and therefore obligate urine output
- Maintain adequate nutrition, especially in children
Medications
- THIAZIDE diuretic (hydrochlorothiazide 25-50 mg or bendroflumethiazide 5 mg) — paradoxically reduces urine volume by 30-50%; works through volume contraction and enhanced proximal sodium reabsorption
- AMILORIDE — first-line ADJUNCT in lithium-induced NDI; blocks lithium entry through ENaC channels in collecting duct
- NSAIDs (indomethacin) — reduce urine output via prostaglandin inhibition; use with caution, especially in CKD; usually short-term
- DESMOPRESSIN — usually ineffective in NDI; can help selected inherited cases at high dose
- Combination therapy (thiazide + amiloride + low-dose NSAID) often used in severe inherited disease
Specific
- Lithium-induced NDI: amiloride is the drug of choice; allows lithium continuation in many cases
- Hypercalcaemia-induced NDI: usually reverses within days-weeks of normalising calcium
- Congenital: lifelong polyuria; meticulous fluid and electrolyte care; family genetic counselling
Special considerations and prognosis
Lithium-specific Advice
- Check renal function and 24h urine volume in any lithium patient with polyuria
- Joint psychiatry-nephrology decision before stopping lithium
- If lithium must continue, add amiloride and monitor closely
- Acute lithium toxicity is a separate emergency — discuss with poisons unit (TOXBASE) and consider haemodialysis if level >2.5 mmol/L
Children With Congenital Ndi
- Specialist paediatric nephrology team
- Free water access at school, structured drinking, frequent toileting
- High-risk during illness — admit early for IV hydration
- Genetic counselling and family planning support
Pregnancy
- Gestational DI usually responds to desmopressin
- Pre-existing NDI: needs increased water intake; obstetric team aware
Prognosis
- Reversible causes: usually full recovery within weeks-months
- Long-standing lithium NDI: may be permanent
- Congenital: lifelong, but normal life expectancy with good management
- Major risk is hypernatraemia in vulnerable settings (post-operative, sedated, demented) — alert teams in advance
KEY MESSAGE: nephrogenic DI is common, treatable and often missed. Any polyuric patient on lithium needs paired osmolalities and a renal opinion.
