What is a first-line medication for lowering severely elevated triglycerides (hypertriglyceridemia) in a patient with impaired renal function (eGFR < 30)?

First-Line Medication for Severe Hypertriglyceridemia in Patients with eGFR <30

Prescription omega-3 fatty acids (4g/day) are the first-line medication for lowering triglycerides >500 mg/dL in patients with eGFR <30 ml/min/1.73m² due to their efficacy and safety profile in severe renal impairment. 1, 2

Understanding Severe Hypertriglyceridemia in CKD

Severe hypertriglyceridemia (≥500 mg/dL) in patients with advanced chronic kidney disease (CKD) requires prompt treatment due to:

• High risk of acute pancreatitis when triglycerides exceed 500 mg/dL
• Increased cardiovascular risk
• Limited medication options due to renal impairment

Treatment Algorithm

Step 1: Initial Assessment

• Identify and address secondary causes of hypertriglyceridemia:
  • Poorly controlled diabetes
  • Alcohol consumption
  • Medications (estrogens, corticosteroids)
  • Hypothyroidism

Step 2: Implement Lifestyle Modifications

• Very low-fat diet (10-15% of calories from fat)
• For triglycerides ≥1000 mg/dL, consider extreme fat restriction (<5% of calories)
• Eliminate added sugars and alcohol
• Weight loss if applicable
• Regular physical activity

Step 3: Pharmacological Management

First-Line Therapy: Prescription Omega-3 Fatty Acids

• Dosage: 4g/day (containing EPA+DHA or EPA alone)
• Efficacy: Reduces triglycerides by ≥30% in patients with very high triglycerides 2
• Safety: Well-tolerated with no dose adjustment needed in severe renal impairment 3
• Mechanism: Inhibits diacylglycerol acyltransferase, increases plasma lipoprotein lipase activity, decreases hepatic lipogenesis, and increases hepatic β-oxidation 3

Why NOT Other Options:

1. Fibrates (Fenofibrate):

   • Contraindicated in severe CKD (eGFR <30 ml/min/1.73m²) 4
   • Must be discontinued if eGFR declines to <30 ml/min/1.73m² due to risk of worsening renal function 4

2. Statins:

   • While useful for mild-moderate hypertriglyceridemia, they are not first-line for severe hypertriglyceridemia (>500 mg/dL) 1
   • Primary focus is LDL-C reduction rather than significant triglyceride lowering

3. Niacin:

   • Associated with significant adverse effects
   • Limited evidence in severe CKD

Monitoring and Follow-up

• Check lipid panel 4-6 weeks after initiating therapy
• Monitor for gastrointestinal side effects (most common with omega-3 fatty acids)
• Continue to reinforce dietary and lifestyle modifications

Clinical Pearls and Pitfalls

• Key Advantage: Prescription omega-3 fatty acids don't require dose adjustment in renal impairment and have minimal drug interactions 3
• Pitfall to Avoid: Don't confuse over-the-counter fish oil supplements with prescription omega-3 fatty acids, which contain standardized amounts of EPA and DHA
• Important Distinction: EPA-only formulations don't raise LDL-C in patients with very high triglycerides, while EPA+DHA formulations may increase LDL-C 2
• Safety Note: The American Heart Association advises that therapy with EPA and DHA to lower very high triglyceride levels should be used under physician supervision 5

By using prescription omega-3 fatty acids as first-line therapy for severe hypertriglyceridemia in patients with eGFR <30, you can effectively reduce triglyceride levels while minimizing risks associated with impaired renal function.