How is Diabetes Insipidus (DI) managed and treated?

Management and Treatment of Diabetes Insipidus

Distinguish Central from Nephrogenic DI First

The cornerstone of DI management depends entirely on whether the condition is central (CDI) or nephrogenic (NDI), as treatments are fundamentally different and using the wrong approach can be ineffective or harmful. 1, 2

Diagnostic Differentiation

• Measure plasma copeptin levels as the primary differentiating test: levels <21.4 pmol/L indicate central DI, while levels >21.4 pmol/L indicate nephrogenic DI 1, 2
• Confirm the diagnosis with simultaneous measurement of serum sodium, serum osmolality, and urine osmolality—the combination of urine osmolality <200 mOsm/kg H₂O with high-normal or elevated serum sodium is pathognomonic for DI 1, 3
• Order genetic testing early in suspected nephrogenic cases, particularly in symptomatic females and male offspring of known carriers 2

---

Treatment of Central Diabetes Insipidus

Desmopressin (DDAVP) is the treatment of choice for central DI and should be initiated once the diagnosis is confirmed and serum sodium is verified as normal. 1, 2, 4

Desmopressin Dosing and Administration

• Start treatment-naïve patients at 2-4 mcg daily administered as one or two divided subcutaneous or intravenous doses 4
• Adjust morning and evening doses separately to achieve adequate diurnal rhythm of water turnover 4
• For patients switching from intranasal desmopressin, use 1/10th the daily maintenance intranasal dose as the starting parenteral dose 4
• Titrate based on adequate sleep duration and appropriate (not excessive) water turnover 4

Critical Safety Monitoring for Desmopressin

• Verify serum sodium is normal before starting or resuming desmopressin—this is mandatory 4
• Measure serum sodium within 7 days and approximately 1 month after initiating therapy, then periodically during treatment 4
• Monitor more frequently in patients ≥65 years and those at increased risk of hyponatremia 4
• Initiate fluid restriction during desmopressin treatment to prevent life-threatening hyponatremia, which can cause seizures, coma, respiratory arrest, or death 4, 5

Important Caveat

• Desmopressin is completely ineffective for nephrogenic DI and should never be used for this condition 4

---

Treatment of Nephrogenic Diabetes Insipidus

For symptomatic nephrogenic DI, initiate combination therapy with thiazide diuretics plus NSAIDs (prostaglandin synthesis inhibitors), along with dietary modifications. 1, 2

Pharmacological Approach

• Start thiazide diuretics as first-line treatment—they induce mild volume depletion, increasing proximal sodium and water reabsorption, which can reduce diuresis by up to 50% 2, 3
• Add prostaglandin synthesis inhibitors (NSAIDs) to enhance collecting duct water permeability 2
• Use gastric acid inhibitors concurrently with nonselective cyclooxygenase inhibitors to prevent GI complications 3
• Add amiloride if thiazides cause hypokalemia, which is common and can worsen the concentrating defect 3

Essential Dietary Modifications

• Prescribe a low-salt diet (≤6 g/day) to enhance thiazide effectiveness 1, 2, 3
• Restrict protein intake to <1 g/kg/day to decrease renal solute load and obligatory water excretion 1, 2
• Avoid excessive salt supplementation, as it worsens polyuria and risks hypernatremic dehydration 3

---

Universal Management Principles for All DI Types

All patients with DI must have unrestricted free access to water—this is the absolute cornerstone of preventing life-threatening complications. 1, 2, 3

Fluid Management

• Patients capable of self-regulating should determine fluid intake based on thirst sensation rather than prescribed amounts 1, 2
• Free access to fluid prevents dehydration, hypernatremia, growth failure, and constipation 1, 2, 3
• Hypernatremic dehydration can develop rapidly if water access is restricted 3

Monitoring and Follow-up Schedule

Infants (0-12 months):

• Clinical follow-up including weight and height measurements every 2-3 months 1
• Blood tests (sodium, potassium, chloride, bicarbonate, creatinine, uric acid) every 2-3 months 1
• Urinalysis including osmolality annually 1

Adults:

• Annual clinical follow-up including weight measurements 1
• Annual blood tests (sodium, potassium, chloride, bicarbonate, creatinine, uric acid) 1
• Annual urinalysis including osmolality, protein-creatinine or albumin-creatinine ratio, and 24-hour urine volume 1

All patients:

• Renal ultrasound at least every 2 years to monitor for urinary tract dilation or bladder dysfunction from chronic polyuria 1
• Interval can be extended to 5 years for stable patients 1
• Perform ultrasound before and after bladder emptying, as dilation improves with double voiding in about one-third of patients 1

Long-term Complications

• Approximately 50% of adult patients with DI develop chronic kidney disease stage ≥2, requiring nephrology follow-up according to KDIGO guidelines 1
• All patients with newly developed hormonal deficiencies should undergo MRI with pituitary or sella slices, especially in DI, as it is most commonly caused by metastatic diseases 1

Multidisciplinary Care

• Manage patients with a team including nephrologist, dietitian, psychologist, social worker, and urologist 1
• For infants and young children, provide support from an experienced dietitian to ensure nutritional adequacy and practical advice on energy supplementation 2
• Consider tube feeding (nasogastric or gastrostomy) case-by-case for repeated vomiting/dehydration episodes or growth failure in infants and young children 2