What is the treatment for Nephrogenic Diabetes Insipidus (NDI)?

Treatment of Nephrogenic Diabetes Insipidus

The cornerstone of treating nephrogenic diabetes insipidus involves free access to fluids, dietary salt and protein restriction (≤6 g/day salt, <1 g/kg/day protein), and pharmacological therapy with thiazide diuretics combined with prostaglandin synthesis inhibitors (NSAIDs or COX-2 inhibitors) in symptomatic patients. 1

Fluid Management

• Unrestricted fluid access is absolutely essential in all NDI patients to prevent life-threatening dehydration, hypernatremia, and growth failure 1, 2
• Patients capable of self-regulation should drink according to thirst rather than prescribed amounts 2
• In infants, prioritize normal-for-age milk intake over water to ensure adequate caloric intake 1, 2
• Consider tube feeding (nasogastric or gastrostomy) in infants with repeated vomiting, dehydration episodes, or failure to thrive—approximately 20-30% of children require this intervention 1

Dietary Modifications

Reducing renal osmotic load through dietary restriction is critical for minimizing urine volume:

• Salt restriction: ≤6 g/day in adults; age-specific targets in children (1 g/day for infants 0-1 year, 2 g/day for ages 1-3 years, 3 g/day for ages 4-6 years, 5 g/day for ages 7-10 years) 1
• Protein restriction: <1 g/kg/day in adults; age-specific targets in children (1.8 g/kg/day for 0-1 months, decreasing to 0.85 g/kg/day by age 11+) 1
• Critical caveat: Excessive restriction can compromise growth in children—balance is essential 1
• Every patient requires dietetic counseling from an experienced dietitian 1

Pharmacological Treatment

First-Line Therapy: Thiazide Diuretics + Prostaglandin Synthesis Inhibitors

In symptomatic infants and children, start combination therapy with thiazides and COX inhibitors 1:

• Thiazide diuretics (hydrochlorothiazide 25 mg once or twice daily in adults) reduce urine output by up to 50% short-term when combined with low-salt diet 1

  • Mechanism: Induce mild volume depletion, increasing proximal sodium and water reabsorption 1
  • Salt restriction potentiates diuretic efficacy 1

• Prostaglandin synthesis inhibitors enhance collecting duct water permeability 1

  • Selective COX-2 inhibitors (celecoxib) reduce gastrointestinal bleeding risk compared to non-selective NSAIDs 1
  • Critical safety consideration: Discontinue COX inhibitors at age ≥18 years or earlier if full continence achieved due to nephrotoxicity concerns 1
  • Contraindicated during pregnancy 3

Adjunctive Therapy: Amiloride

• Add amiloride to thiazide therapy in patients who develop thiazide-induced hypokalemia 1
• Amiloride impairs urinary dilution in the collecting duct 1

Important Treatment Considerations

• Most patients do not experience significant changes in urine volume after discontinuing medications in adulthood, though some report increased drinking and fatigue 1
• Ongoing treatment decisions should balance efficacy against side effects (hypokalemia, gout, hypercholesterolemia, non-melanoma skin cancer) 1
• Desmopressin is ineffective for nephrogenic diabetes insipidus as the kidneys are unresponsive to vasopressin 4—though one case report suggests potential benefit in lithium-induced NDI when combined with thiazides and NSAIDs 5

Emergency Management

Hypernatremic dehydration is the typical NDI emergency:

• Use 5% dextrose in water for IV rehydration—never use 0.9% NaCl as its osmotic load (300 mOsm/kg) far exceeds typical NDI urine osmolality (100 mOsm/kg), risking severe hypernatremia 1, 2
• Start at maintenance rate (children: 100 ml/kg/24h for first 10 kg, 50 ml/kg/24h for 10-20 kg, 20 ml/kg/24h for remaining weight; adults: 25-30 ml/kg/24h) 1
• Monitor blood glucose regularly as dextrose infusion can cause hyperglycemia with osmotic diuresis 1
• Every patient should carry an emergency plan with IV fluid management instructions 6, 2

Monitoring and Follow-Up

Regular surveillance is essential to prevent complications:

• Kidney ultrasound every 2 years to detect urinary tract dilatation ("flow uropathy") and bladder dysfunction—urological complications occur in 46% of patients 1, 2
• Biochemical monitoring: Serum Na, K, Cl, HCO₃, creatinine, uric acid every 2-3 months in infants, every 3-12 months in children, annually in adults 1
• Growth monitoring: Weight and height every 2-3 months in infants, every 3 months in children 1
• Treatment efficacy assessment: Urine osmolality, urine output, weight gain, and growth 1

Multidisciplinary Care

• NDI management requires a team including nephrologist, dietitian, psychologist, social worker, and urologist 1
• Toilet training proceeds as in other children, though full continence typically occurs only in the second decade of life 1