What other medications are commonly prescribed in pediatric patients with Chronic Kidney Disease (CKD) besides Angiotensin-Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs)?

Common Medications for Pediatric CKD Patients Beyond ACEi/ARBs

Beyond ACE inhibitors and ARBs, pediatric CKD patients commonly require multiple medications to manage comorbidities, with treatment complexity increasing with CKD progression and the presence of glomerular disease. 1, 2

First-Line Antihypertensive Medications

ACE inhibitors and ARBs remain the first-line antihypertensive agents in pediatric CKD due to their:

• Largest evidence base for efficacy and safety in pediatric patients with renal hypertension
• Superior efficacy in patients with proteinuria
• Ability to slow CKD progression 3

However, when these are insufficient or contraindicated, other antihypertensive medications are commonly prescribed:

Additional Antihypertensive Options

1. Calcium Channel Blockers

   • Amlodipine: Starting dose 2.5 mg/day (children 6-17 years), maximum 5 mg/day
   • Isradipine: Starting dose 0.15-0.2 mg/kg/day, maximum 0.8 mg/kg/day up to 20 mg/day
   • Felodipine: Starting dose 2.5 mg/day, maximum 10 mg/day
   • Caution: Use with care in ADPKD as some studies suggest they may promote cyst growth 3, 1

2. Beta-Blockers

   • Metoprolol: Starting dose 1 mg/kg/day (for children ≥6 years), maximum 2 mg/kg/day up to 200 mg/day
   • Atenolol: Starting dose 0.5-1 mg/kg/day, maximum 2 mg/kg/day up to 100 mg/day
   • Caution: Not recommended as initial therapy due to adverse effect profile 3, 1

3. Diuretics

   • Hydrochlorothiazide: Starting dose 1 mg/kg/day, maximum 3 mg/kg/day up to 50 mg/day
   • Furosemide: Starting dose 0.5-2.0 mg/kg/day, maximum 6 mg/kg/day
   • Caution: May increase vasopressin levels and potentially worsen GFR in ADPKD; monitor electrolytes closely 3, 1

Management of Anemia

Erythropoiesis-Stimulating Agents (ESAs) are standard therapy for anemia in pediatric CKD:

• Epoetin alfa: FDA-approved for pediatric CKD patients aged 1 month to 16 years requiring dialysis 4, 5

  • Use single-dose vials (benzyl alcohol-free) for neonates and infants
  • Multiple-dose vials are contraindicated in neonates and infants due to benzyl alcohol content
  • Monitor hemoglobin levels regularly

• Darbepoetin alfa: Longer half-life allowing less frequent administration 6

Mineral and Bone Disorder Management

1. Phosphate Binders:

   • Calcium-based binders (calcium carbonate, calcium acetate)
   • Non-calcium-based binders (sevelamer, lanthanum)

2. Vitamin D Analogs:

   • Calcitriol
   • Paricalcitol
   • Doxercalciferol

3. Calcimimetics:

   • Cinacalcet: Not established for safety and efficacy in pediatric patients
   • Studies in pediatric CKD patients were insufficient to establish safe and effective dosing regimens 7

Medication Adherence Considerations

• Nonadherence is associated with increased medication dosing frequency (>2 times/day) rather than the number of medications 2
• Consider consolidating medication regimens to improve adherence
• Monitor for drug interactions, particularly with dual RAAS blockade (ACEi + ARB), which is generally not recommended due to increased risk of hyperkalemia and acute kidney injury 3, 1

Important Monitoring Parameters

1. For ACEi/ARB therapy:

   • Check serum creatinine, potassium, and blood pressure within 2-4 weeks of initiation or dose increase 3, 1
   • Continue therapy unless serum creatinine rises by more than 30% within 4 weeks 3

2. For blood pressure management:

   • Target 24-hour mean arterial pressure ≤50th percentile on ambulatory blood pressure monitoring 3
   • When ABPM not available, target manual office systolic BP 50th-75th percentile 3

3. For diuretic therapy:

   • Monitor electrolytes shortly after initiating therapy and periodically thereafter 3
   • Potassium-sparing diuretics may cause severe hyperkalemia, especially if given with an ACEi or ARB 3

Clinical Pitfalls to Avoid

1. Avoid dual RAAS blockade (ACEi + ARB) in routine practice due to increased risk of hyperkalemia and acute kidney injury without proven additional benefit 3, 1

2. Use calcium channel blockers with caution in ADPKD patients due to potential cyst growth promotion 3, 1

3. Be cautious with diuretics as they may increase vasopressin levels and potentially worsen GFR in certain conditions like ADPKD 3, 1

4. For ESAs, use single-dose vials (benzyl alcohol-free) for neonates and infants to avoid serious adverse reactions including the "gasping syndrome" 4

5. Do not restrict protein intake in children with CKD due to the risk of growth impairment 1