Primary Treatment for Nephrogenic Diabetes Insipidus (NDI)
The primary treatment for Nephrogenic Diabetes Insipidus consists of free access to fluids, dietary modifications (low salt ≤6 g/day and low protein <1 g/kg/day), and pharmacological therapy with thiazide diuretics combined with prostaglandin synthesis inhibitors for symptomatic patients. 1, 2
Non-Pharmacological Management
Fluid Management
- Free access to fluid is essential in all patients with NDI to prevent dehydration, hypernatraemia, growth failure, and constipation 1, 2
- Patients capable of self-regulating should determine their fluid intake based on thirst sensation rather than prescribed amounts 2
- For infants, normal-for-age milk intake (instead of water) is recommended to guarantee adequate caloric intake 1
- Tube feeding should be considered in infants and children with repeated episodes of vomiting, dehydration, and/or failure to thrive 1, 2
Dietary Modifications
- A low salt (≤6 g/day) and protein diet (<1 g/kg/day) is recommended to reduce renal osmotic load and minimize urine volume 1, 2
- Every patient with NDI should receive dietetic counselling from a dietitian experienced with the disease 1
- Age-specific dietary recommendations should be followed (see below) 1:
- Infants (0-1 year): 1 g salt/day, protein 1.3-1.8 g/kg/day based on age
- Children 1-3 years: 2 g salt/day, protein 1.1 g/kg/day
- Children 4-6 years: 3 g salt/day, protein 0.95 g/kg/day
- Children 7-10 years: 5 g salt/day, protein 0.95 g/kg/day
- Children >11 years and adults: <6 g salt/day, protein <1 g/kg/day
Pharmacological Treatment
First-Line Medications
- For symptomatic infants and children, treatment should start with a thiazide diuretic and prostaglandin synthesis inhibitor (cyclooxygenase/COX inhibitor) 1, 2
- Thiazide diuretics act by inducing mild volume depletion, reducing diuresis by up to 50% in the short term when combined with a low-salt diet 1, 3
- The paradoxical antidiuretic effect of thiazides occurs through increased proximal tubular reabsorption of water and sodium 3, 4
Adjunctive Therapy
- Amiloride should be added to thiazide in patients who develop hypokalemia induced by thiazides 1, 2, 5
- Amiloride has been shown to increase renal concentrating ability and reduce polyuria, particularly in lithium-induced NDI 5
Treatment Considerations
- Treatment efficacy can be evaluated via urine osmolality, urine output, weight gain, and growth 1, 2
- Close monitoring of fluid balance, weight, and biochemistry is recommended at the start of treatment due to risk of hyponatraemia if fluid intake remains high 1
- Prostaglandin synthesis inhibitors should be discontinued once patients reach adulthood (≥18 years), or earlier if complete continence is achieved, due to concerns of nephrotoxicity 1, 2
- Prostaglandin synthesis inhibitors are contraindicated during pregnancy 1, 2
Monitoring and Follow-up
- Regular assessment of weight and height is recommended (every 2-3 months for infants, every 3 months for children, annually for adults) 1, 2
- Blood tests (Na, K, Cl, HCO3, creatinine, uric acid) should be performed regularly (every 2-3 months for infants, every 3-12 months for children, annually for adults) 1, 2
- Kidney ultrasound should be performed at least once every 2 years to monitor for urinary tract dilatation and/or bladder dysfunction caused by polyuria 1, 2
- Patients with NDI should be followed by a multidisciplinary team including a nephrologist, dietitian, psychologist, social worker, and urologist 1
Emergency Management
- Intravenous rehydration with water and dextrose (e.g., 5% dextrose) is recommended for hypernatraemic dehydration 1, 2
- Salt-containing solutions, especially NaCl 0.9%, should be avoided due to their large renal osmotic load 1
- Each patient should have an emergency plan, including a letter explaining their diagnosis with advice regarding intravenous fluid management 2