What are the management strategies for Bartter syndrome?

Management of Bartter Syndrome

The cornerstone of Bartter syndrome management includes salt supplementation, potassium supplementation, and nonsteroidal anti-inflammatory drugs (NSAIDs), with treatment tailored to the specific subtype and severity of the condition. 1

First-Line Treatments

Salt and Electrolyte Supplementation

• Oral sodium chloride supplementation is essential to address the primary salt-wasting defect 1
• Potassium chloride supplementation is required to manage hypokalemia, which can lead to muscle weakness, cardiac arrhythmias, and growth failure 1
• Magnesium supplementation may be necessary, especially in patients with concurrent hypomagnesemia 1, 2

NSAIDs

• NSAIDs inhibit prostaglandin formation, addressing the underlying pathophysiology of Bartter syndrome 1
• Commonly used NSAIDs include:
  • Indomethacin (1-4 mg/kg/day divided in 3-4 doses) 1
  • Ibuprofen (15-30 mg/kg/day in 3 doses) 1
  • Celecoxib (2-10 mg/kg/day in 2 doses) - a selective COX-2 inhibitor 1
• Euvolemia should be achieved before initiating NSAIDs to reduce potential nephrotoxicity 1
• Gastric acid suppression should accompany non-selective COX inhibitors to prevent gastrointestinal side effects 1
  • If proton pump inhibitors are used, monitor for hypomagnesemia 1
  • Consider H2 blockers or conversion to COX-2 inhibitors if PPI-associated hypomagnesemia develops 1

Medications to Avoid or Use with Caution

• K-sparing diuretics, ACE inhibitors, and angiotensin receptor blockers should not be routinely used despite their ability to ameliorate electrolyte abnormalities 1

  • These medications can worsen salt wasting and risk critical hypovolemia 1
  • Consider only in individual cases with severe symptoms despite maximization of standard therapy 1

• Thiazide diuretics should not be routinely administered despite occasional use to reduce calcium excretion 1

  • No data supports their efficacy in Bartter syndrome 1
  • They may lead to life-threatening hypovolemia by inhibiting compensatory salt reabsorption in the distal convoluted tubule 1

Special Considerations

Growth Hormone Therapy

• Consider growth hormone therapy for children with persistent growth retardation despite optimized metabolic control 1, 3
• Optimize metabolic control with COX inhibitors before starting recombinant human GH 1
• Growth hormone deficiency has been reported in Bartter syndrome, particularly in BS3 subtype 1

Pregnancy Management

• Establish joint management between nephrology and obstetrics for pregnant women 1
• Serum potassium levels normally decrease by 0.2-0.5 mmol/L around midgestation 1
• Target plasma potassium level of 3.0 mmol/L during pregnancy (though this may not be achievable in all patients) 1
• Renin-angiotensin system blockers are contraindicated and NSAIDs are discouraged during pregnancy 1
• Monitor electrolytes during labor and consider hospital delivery to reduce maternal complications 1

Cardiac Monitoring

• Perform electrocardiography to assess rhythm and QT-interval duration due to risk of ventricular arrhythmias from hypokalemia and hypomagnesemia 1, 2
• Consider further cardiac workup (Holter, stress ECG) for patients with palpitations, syncope, or persistent ECG abnormalities 1
• Use caution with medications that slow sinus rhythm, affect QT interval, or potentially induce hypomagnesemia 1

Follow-Up Recommendations

Children

• Follow infants and young children every 3-6 months 1
• Older children with stable condition should be seen every 6-12 months 1
• Monitor for dehydration, polyuria, muscle weakness, growth, and psychomotor development 1
• Biochemical workup should include acid-base status, electrolytes (including bicarbonate, chloride, magnesium), renal function, PTH, and urinary calcium excretion 1
• Assess urine osmolality to test for secondary nephrogenic diabetes insipidus 1
• Perform renal ultrasound every 12-24 months to monitor for nephrocalcinosis, kidney stones, and obstructive uropathy 1, 4

Adults

• Follow adult patients every 6-12 months 1
• Monitor for dehydration, polyuria, muscle weakness, fatigue, and palpitations 1
• Include microalbuminuria in biochemical workup 1
• Perform renal ultrasound every 12-24 months 1

Long-Term Complications and Monitoring

• Chronic kidney disease is common, particularly in BS1 and BS4 subtypes 1
• Risk factors for chronic kidney injury include:
  • Premature birth/low birth weight 1
  • Nephrocalcinosis 1
  • Chronic dehydration 1
  • Progressive proteinuria related to hyperfiltration 1
  • NSAID treatment 1
• Monitor for NSAID side effects, including gastrointestinal complications (gastritis, ulcers) and renal function decline 5
• Consider tapering or discontinuing NSAIDs in stable patients if risks outweigh benefits 1
• Evaluate quality of life using age-appropriate scales from age 5 years onward at 2-year intervals 1

Patient Education

• Provide disease-specific education through age-appropriate personal education, information leaflets, and support groups 1
• Establish "sick day rules" for intercurrent illness management 1
• Address potential school performance issues related to BS or complications from extreme prematurity 1