What is the treatment for Diabetes Insipidus (DI) in adults?

Treatment of Diabetes Insipidus in Adults

The treatment of diabetes insipidus in adults depends fundamentally on whether the condition is central (vasopressin deficiency) or nephrogenic (vasopressin resistance), with desmopressin being the definitive treatment for central DI and thiazide diuretics combined with dietary modifications being first-line for nephrogenic DI. 1, 2, 3

Universal Management Principle for All DI Types

Free access to water is absolutely essential for all adults with diabetes insipidus to prevent life-threatening dehydration, hypernatremia, and associated complications. 1, 2, 3 Adults capable of self-regulating should determine their fluid intake based on thirst sensation rather than prescribed amounts. 3 Never restrict fluids in DI patients, as this causes life-threatening hypernatremia and dehydration. 2

Central Diabetes Insipidus Treatment

Pharmacologic Management

Desmopressin (DDAVP) is the treatment of choice for central diabetes insipidus in adults. 2, 3, 4

• Intranasal dosing: The usual adult dosage range is 0.1 mL to 0.4 mL daily (10-40 mcg), either as a single dose or divided into two or three doses, with most adults requiring 0.2 mL daily in two divided doses. 4
• The morning and evening doses should be separately adjusted to achieve an adequate diurnal rhythm of water turnover. 4
• Approximately 25-33% of patients can be controlled by a single daily dose. 4
• Fluid restriction should be observed during desmopressin therapy to prevent hyponatremia. 4

Alternative Routes When Intranasal Route Compromised

Injectable desmopressin should be used when the intranasal route is compromised by nasal congestion, nasal discharge, atrophy of nasal mucosa, severe atrophic rhinitis, impaired consciousness, or following cranial surgical procedures such as transsphenoidal hypophysectomy. 4

Monitoring Response

Response should be estimated by two parameters: adequate duration of sleep and adequate (not excessive) water turnover. 4 Continued response can be monitored by urine volume and osmolality. 4

Nephrogenic Diabetes Insipidus Treatment

First-Line Pharmacologic Therapy

For symptomatic adults with nephrogenic DI, thiazide diuretics are the first-line treatment. 1, 2, 3

• Thiazides induce mild volume depletion, increasing proximal sodium and water reabsorption, thereby reducing water delivery to the collecting tubules and decreasing urine output by up to 50% in the short term. 5
• Important caveat: In the long term, a much more moderate reduction in urine volume is typically observed. 5
• Amiloride should be added if thiazides cause hypokalemia, which is common and can worsen the concentrating defect. 1

Prostaglandin Synthesis Inhibitors (NSAIDs)

Prostaglandin synthesis inhibitors (cyclooxygenase inhibitors) can be combined with thiazides for symptomatic patients. 5, 1, 2 However, the extent to which chronic NSAID use contributes to progression of chronic kidney disease remains unclear, as approximately 50% of adult NDI patients develop CKD stage ≥2. 5

Essential Dietary Modifications

A low-salt diet (≤6 g/day) enhances the effect of thiazide diuretics and is essential for managing nephrogenic DI. 1, 3

Reduced protein intake (<1 g/kg/day) decreases renal solute load and subsequent obligatory water excretion. 1, 3

Treatment Monitoring and Adjustment

• Close monitoring of fluid balance, weight, and biochemistry is essential when starting treatment, as marked hyponatremia can occur if patients maintain unchanged high fluid intake after commencing drug treatment. 5
• Regular assessment of serum sodium, potassium, and renal function is necessary. 1
• Drug treatment efficacy often decreases with age—treatment with at least one medication decreased from 85% in childhood to 56% in adulthood, likely reflecting perceived lack of efficacy and/or concern about side effects. 5
• Regular assessment of ongoing drug treatment should be based on a careful balance of risks and benefits. 5

Critical Monitoring for All Adult DI Patients

Biochemical Monitoring

• Measure serum sodium, serum osmolality, and urine osmolality as initial biochemical work-up. 5
• Regular assessment of serum electrolytes, serum creatinine, and uric acid is recommended. 3
• Annual urinalysis including osmolality, protein-creatinine or albumin-creatinine ratio, and 24-hour urine volume. 3

Imaging Surveillance

Renal ultrasound should be performed at least every 2 years to monitor for urinary tract dilatation or bladder dysfunction from chronic polyuria. 1, 3 The interval can be extended to 5 years for stable patients. 3 Ultrasound should be performed before and after bladder emptying, as dilation improves with double voiding in about one-third of patients. 3

Renal Function Monitoring

Adults with DI have increased risk of chronic kidney disease and require follow-up according to KDIGO guidelines if CKD develops. 3

Emergency Preparedness

Each adult DI patient should have an emergency plan including a letter explaining their diagnosis with IV fluid management advice and contact information. 2 A medical alert bracelet or card is recommended. 2

For IV rehydration, use water with dextrose or glucose (5% dextrose), not normal saline. 2 Calculate initial IV fluid rate to avoid decreasing serum sodium >8 mmol/L/day in hypertonic dehydration. 2

Special Considerations for Older Adults

In elderly patients, this drug is substantially excreted by the kidney, and the risk of toxic reactions may be greater in those with impaired renal function. 4 Care should be taken in dose selection, and monitoring renal function may be useful. 4