What is the diagnosis and treatment approach for a child with diabetes insipidus?

Diabetes Insipidus in Children: Diagnosis and Management

Diagnostic Approach

Suspect diabetes insipidus in any child presenting with polyuria, polydipsia, failure to thrive, and hypernatremic dehydration with inappropriately dilute urine (osmolality <200 mOsm/kg H₂O). 1, 2

Initial Biochemical Work-Up

• Measure serum sodium, serum osmolality, and urine osmolality simultaneously as the first-line diagnostic tests 1, 2
• The combination of urine osmolality <200 mOsm/kg H₂O with high-normal or elevated serum sodium (>145 mEq/L) is pathognomonic for diabetes insipidus 3
• Obtain 24-hour urine volume measurement to quantify polyuria (>3 L/24h in adults, >4 mL/kg/hr in children) 4, 3

Distinguishing Central from Nephrogenic DI

• Plasma copeptin measurement is the primary test to differentiate between central and nephrogenic diabetes insipidus 3, 2
  • Copeptin >21.4 pmol/L indicates nephrogenic diabetes insipidus 3, 2
  • Copeptin <21.4 pmol/L suggests central diabetes insipidus or primary polydipsia 3, 2
• Alternatively, a desmopressin trial can differentiate: response (urine osmolality increase >50%) indicates central DI, while no response indicates nephrogenic DI 3, 5

Additional Diagnostic Testing

• Perform early genetic testing in suspected nephrogenic diabetes insipidus using a multigene panel including AVPR2, AQP2, and AVP genes 1, 2
• For suspected central diabetes insipidus, obtain MRI of the pituitary with dedicated sella sequences to identify structural causes (tumors, infiltrative diseases) present in approximately 50% of cases 3
• The absence of posterior pituitary bright signal on MRI is pathognomonic for central diabetes insipidus 4

Management of Central Diabetes Insipidus

Desmopressin is the treatment of choice for central diabetes insipidus. 6, 5

Desmopressin Dosing

• Starting dose: 2-4 mcg daily administered as one or two divided doses by subcutaneous or intravenous injection 6
• Adjust morning and evening doses separately to achieve adequate diurnal rhythm of water turnover 6
• For patients switching from intranasal desmopressin, start with 1/10th the daily maintenance intranasal dose 6
• Titrate dose based on adequate sleep duration and appropriate (not excessive) water turnover 6

Critical Monitoring Requirements

• Ensure serum sodium is normal before starting or resuming desmopressin 6
• Measure serum sodium within 7 days and at 1 month after initiating therapy, then periodically during treatment 6, 3
• Monitor more frequently in patients at increased risk of hyponatremia 6
• Initiate fluid restriction during desmopressin treatment to prevent hyponatremia 6

Critical Pitfall to Avoid

Extreme caution is required when treating infants and small children with desmopressin due to the danger of fluid overload and life-threatening hyponatremia. 5, 6 Hyponatremia can lead to seizures, coma, respiratory arrest, or death 6

Management of Nephrogenic Diabetes Insipidus

Desmopressin is ineffective and contraindicated in nephrogenic diabetes insipidus. 6 Management requires a multimodal approach combining dietary modifications and pharmacotherapy.

Fluid Management (Highest Priority)

• Free access to fluid 24/7 is essential in all patients with nephrogenic DI to prevent dehydration, hypernatremia, growth failure, and constipation 1, 2
• Patients capable of self-regulation should determine fluid intake based on thirst sensation rather than prescribed amounts, as their osmosensors are more sensitive and accurate than any medical calculation 1, 3, 2
• For infants, provide normal-for-age milk intake (instead of water) to guarantee adequate caloric intake 1, 2
• When fasting is required (>4 hours, e.g., before anesthesia), administer intravenous 5% dextrose in water at maintenance rate with close monitoring of weight, fluid balance, and biochemistry 1, 2

Dietary Modifications

Every patient with nephrogenic DI requires dietetic counseling from a dietitian experienced with the disease. 1

• Implement a low-salt diet (≤6 g/day for adults, age-appropriate for children) and protein restriction (<1 g/kg/day for adults, age-appropriate for children) to reduce renal osmotic load and minimize urine volume 1, 2
• Specific age-based recommendations 1:
  • 0-1 year: 1 g salt/day (0.4 g sodium), 1.3-1.8 g protein/kg/day
  • 1-3 years: 2 g salt/day (0.8 g sodium), 1.1 g protein/kg/day
  • 4-6 years: 3 g salt/day (1.2 g sodium), 0.95 g protein/kg/day
  • 7-10 years: 5 g salt/day (2 g sodium), 0.95 g protein/kg/day

  • 11 years: <6 g salt/day (2.4 g sodium), 0.85 g protein/kg/day

• Excessive restriction of salt and protein can compromise growth 1

Pharmacological Treatment

In symptomatic infants and children with nephrogenic DI, start combination treatment with thiazide diuretics and prostaglandin synthesis inhibitors (NSAIDs). 1, 2

• Thiazide diuretics combined with low-salt diet can reduce diuresis by up to 50% in the short term 1, 2
• The mechanism involves mild volume depletion leading to increased proximal sodium and water reabsorption 1
• Add amiloride to thiazide in patients who develop hypokalaemia 1, 2
• Discontinue COX inhibitors once patients reach adulthood (≥18 years) or earlier if full continence is achieved due to concerns of nephrotoxicity 1
• Salt restriction potentiates the efficacy of diuretics 1

Tube Feeding Considerations

• Consider tube feeding (nasogastric or gastrostomy) in infants and children with repeated episodes of vomiting, dehydration, and/or failure to thrive 1, 2
• In retrospective studies, 20-30% of children with nephrogenic DI received tube feeding at some point, with approximately 25% having gastrostomy 1
• Tube feeding is rarely continued beyond 4 years of age 1
• "Greedy" drinking followed by vomiting is commonly reported in infants, thought to reflect gastroesophageal reflux exacerbated by large fluid volumes 1

Treatment Efficacy Monitoring

Evaluate treatment efficacy via urine osmolality, urine output, weight gain, and growth. 1, 2

Ongoing Monitoring and Follow-Up

Clinical Follow-Up Schedule

• Infants (0-12 months): Clinical follow-up including weight and height measurements every 2-3 months 3
• Adults: Annual clinical follow-up including weight measurements 3

Laboratory Monitoring

• Infants (0-12 months): Blood tests (sodium, potassium, chloride, bicarbonate, creatinine, uric acid) every 2-3 months 3
• Adults: Annual blood tests including sodium, potassium, chloride, bicarbonate, creatinine, and uric acid 3
• Urinalysis including osmolality should be performed annually 3

Imaging Surveillance

Perform kidney ultrasound at least once every 2 years to monitor for urinary tract dilatation and/or bladder dysfunction caused by polyuria. 1, 3, 2

• Urological complications occur in approximately 46% of patients with nephrogenic DI, including nocturnal enuresis ("bed flooding"), incomplete voiding, large bladder capacity, and hydronephrosis 1, 3
• The interval can be extended to 5 years for stable patients 3
• Ultrasound should be performed before and after bladder emptying, as dilatation improves with double voiding in about one-third of patients 3

Multidisciplinary Care

Patients with diabetes insipidus should be managed by a multidisciplinary team including a (pediatric) nephrologist, dietitian, psychologist, social worker, and urologist. 1, 3

Special Considerations in Children

Toilet Training and Continence

• Toilet training should proceed as in any other child, although full continence is usually only reached in the second decade of life 1
• Nocturnal enuresis with "bed flooding" is common due to large urine volumes, with continence at night achieved at a median age of 8-11 years 1
• Some parents use "double nappies" (larger adult nappy around child's usual nappy) to contain overnight urine volumes 1

Chronic Kidney Disease Risk

Patients with diabetes insipidus have an increased risk of chronic kidney disease, with approximately 50% of adult patients having CKD stage ≥2. 3 These patients require more frequent follow-up according to KDIGO guidelines 3

Emergency Management

• Each patient with nephrogenic DI should have an emergency plan, including a letter explaining their diagnosis with advice regarding intravenous fluid management 2
• For emergency intravenous rehydration, use 5% dextrose in water (NOT normal saline or electrolyte solutions) 3, 2
• Close observation of clinical status, neurological condition, fluid balance, body weight, and serum electrolytes is essential 2