What is the treatment for diabetes insipidus?

Treatment of Diabetes Insipidus

The treatment of diabetes insipidus depends fundamentally on whether it is central (vasopressin deficiency) or nephrogenic (vasopressin resistance), with desmopressin being the treatment of choice for central DI and thiazide diuretics combined with prostaglandin synthesis inhibitors for nephrogenic DI. 1

Initial Assessment and Diagnosis

Before initiating treatment, confirm the type of DI through:

• Measure serum sodium, serum osmolality, and urine osmolality to establish baseline values and confirm inappropriately dilute urine (typically <200 mOsm/kg H₂O) 1, 2
• Plasma copeptin levels distinguish between central and nephrogenic DI: levels <21.4 pmol/L indicate central DI, while levels >21.4 pmol/L suggest nephrogenic DI 2, 3
• Genetic testing is recommended early in suspected nephrogenic DI cases, particularly in symptomatic females and male offspring of known carriers 1
• Brain MRI with pituitary cuts should be performed for all patients with suspected central DI to identify structural causes 2

Treatment of Central Diabetes Insipidus

Desmopressin (DDAVP) Therapy

Desmopressin is the treatment of choice for central DI and can be administered via multiple routes 4, 5, 6:

Dosing Regimens:

• Subcutaneous or intravenous injection: Start with 2-4 mcg daily as one or two divided doses, adjusting separately for morning and evening to achieve adequate diurnal rhythm 4
• For patients switching from intranasal desmopressin: Use 1/10th of the daily intranasal maintenance dose 4
• Oral lyophilisate formulation (melts under tongue) provides better bioavailability than tablets and is now preferred 6

Critical Monitoring Requirements:

Before starting or resuming desmopressin, ensure serum sodium is normal 4. The FDA mandates:

• Measure serum sodium within 7 days and approximately 1 month after initiating therapy, then periodically during treatment 4
• More frequent monitoring in patients ≥65 years and those at increased risk of hyponatremia 4
• Initiate fluid restriction during treatment to prevent dilutional hyponatremia 4, 6

Contraindications and Warnings:

Desmopressin is contraindicated in patients at increased risk of severe hyponatremia, including those with:

• Excessive fluid intake 4
• Illnesses causing fluid or electrolyte imbalances 4
• Concurrent use of loop diuretics or systemic/inhaled glucocorticoids 4

Severe hyponatremia can be life-threatening, leading to seizures, coma, respiratory arrest, or death 4. If hyponatremia occurs, desmopressin may need temporary or permanent discontinuation 4.

Treatment of Nephrogenic Diabetes Insipidus

Desmopressin is ineffective and not indicated for nephrogenic DI 4. Treatment focuses on reducing urine output through:

Pharmacological Approach:

In symptomatic infants and children with nephrogenic DI, start treatment with thiazide diuretics combined with prostaglandin synthesis inhibitors 1:

• Thiazide diuretics with low-salt diet: Can reduce diuresis by up to 50% in the short term through mild volume depletion and increased proximal sodium/water reabsorption 1, 2
• Prostaglandin synthesis inhibitors (NSAIDs): Enhance collecting duct water permeability and should be added to the regimen 1, 2, 7
• Amiloride: Add to thiazide therapy in patients who develop hypokalemia 1, 2

Important Caveats:

• NSAIDs are contraindicated during pregnancy and should be used cautiously in patients with renal impairment 2
• Avoid salt supplementation in secondary nephrogenic DI as it worsens polyuria and risks hypernatremic dehydration 2
• Drug treatment can be very effective in infancy, with reported instances of marked hyponatremia when fluid intake remains unchanged after starting treatment, requiring close monitoring of fluid balance, weight, and biochemistry 1

Dietary Modifications:

• Low-protein diet reduces renal osmotic load and minimizes urine volume 2
• Low-salt diet is essential when using thiazide diuretics 1, 2

Universal Management Principles for All DI Types

Fluid Management:

Free access to fluid is essential in all patients with DI to prevent dehydration, hypernatremia, and associated complications 1, 2:

• Patients capable of self-regulating should determine fluid intake based on thirst sensation rather than prescribed amounts 1, 2, 3
• When fasting is required (>4 hours): Administer intravenous 5% dextrose in water at maintenance rate with close monitoring 2
• Consider urinary catheter placement in acute settings to ensure proper monitoring of diuresis 2

Emergency Preparedness:

Each patient with DI should have an emergency plan, including a letter explaining their diagnosis with advice regarding intravenous fluid management 2.

Ongoing Monitoring:

• Regular assessment of serum electrolytes (sodium, potassium, chloride), urine volume and osmolality, and body weight 2, 3
• Kidney ultrasound at least once every 2 years to monitor for urinary tract dilatation and/or bladder dysfunction caused by polyuria 2, 3

Special Populations

Infants and Young Children:

• Support from an experienced dietitian is recommended to ensure nutritional adequacy and provide practical advice on energy supplementation 1
• Tube feeding (nasogastric or gastrostomy) should be considered case-by-case for repeated vomiting/dehydration episodes or growth failure 1
• Careful spacing of oral feeds and fluids may reduce vomiting from gastro-oesophageal reflux exacerbated by large fluid volumes 1

Post-Acute Tubular Injury:

• Careful attention to volume status is critical as diabetes is an independent risk factor for acute renal failure perioperatively 2
• Avoid salt supplementation in secondary nephrogenic DI following tubular injury 2