What is the best treatment approach for a patient on dialysis with severely elevated triglycerides?

Management of Severely Elevated Triglycerides in Dialysis Patients

For dialysis patients with severely elevated triglycerides, therapeutic lifestyle changes should be the primary intervention, as statins and fibrates are generally not recommended to be initiated in this population. 1

Guideline-Based Approach for Dialysis Patients

Primary Recommendation: Avoid Initiating New Lipid-Lowering Medications

The KDIGO guidelines explicitly recommend against initiating statins or statin/ezetimibe combinations in adults with dialysis-dependent CKD. 1 This recommendation applies regardless of triglyceride levels, as the evidence for cardiovascular benefit in dialysis patients is lacking 1.

• If the patient is already on a statin or fibrate at the time of dialysis initiation, these agents should be continued rather than stopped 1.
• The rationale is that large randomized trials have not demonstrated cardiovascular benefit from initiating lipid-lowering therapy in dialysis patients 1.

Therapeutic Lifestyle Changes as First-Line Treatment

For dialysis patients with hypertriglyceridemia, therapeutic lifestyle changes should be advised as the primary intervention. 1

Specific Dietary Modifications Based on Triglyceride Severity:

• For moderate hypertriglyceridemia (200-499 mg/dL): Restrict added sugars to <6% of total daily calories and limit total fat to 30-35% of total daily calories 2.
• For severe hypertriglyceridemia (500-999 mg/dL): Restrict dietary fat to 20-25% of total calories and eliminate added sugars completely 2.
• For very severe hypertriglyceridemia (≥1000 mg/dL): Implement a very low-fat diet (10-15% of total calories) and eliminate all added sugars 2.

Additional Lifestyle Interventions:

• Complete alcohol abstinence is mandatory for severe hypertriglyceridemia (≥500 mg/dL) to prevent hypertriglyceridemic pancreatitis 2.
• Target 5-10% weight loss if overweight, which can reduce triglycerides by 20% 2.
• Engage in at least 150 minutes/week of moderate-intensity aerobic activity 2.

Addressing Secondary Causes in Dialysis Patients

Aggressively evaluate and treat secondary causes of hypertriglyceridemia before considering pharmacotherapy: 2

• Optimize glycemic control in diabetic patients, as poor glucose control is often the primary driver of severe hypertriglyceridemia and can be more effective than lipid medications 2.
• Screen for and treat hypothyroidism 2.
• Review medications that raise triglycerides (thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids) and substitute if possible 2.

Special Considerations for Dialysis Patients

Dietary Challenges in the Dialysis Population

Incorporating standard heart-healthy foods can be problematic for dialysis patients due to potassium and phosphorus restrictions. 1

• Foods enriched in alpha-linolenic acid (flaxseed, walnuts, soy) are high in potassium and contribute dietary protein and phosphorus, making them unreliable sources of omega-3 fatty acids 1.
• Alternatively, oils from these foods (walnut and flaxseed oils) as well as canola oil can be safely incorporated into the dialysis diet 1.
• Choose lean fish or seafood rather than fatty fish when fat intake must be severely restricted 2.

Omega-3 Fatty Acid Supplementation

For well-nourished, stable dialysis patients, including food sources of omega-3 fatty acids at least twice weekly is beneficial. 1

• Prescription omega-3 fatty acids (2-4g/day) can be considered as adjunctive therapy for severe hypertriglyceridemia, though evidence in dialysis patients is limited 2.
• The AI for alpha-linolenic acid is 1.6 g for men and 1.1 g for women, with up to 10% consumed as EPA and/or DHA 1.

When Pharmacotherapy Might Be Considered

Fibrate Use in Dialysis Patients: Proceed with Extreme Caution

While guidelines recommend against initiating new lipid-lowering therapy in dialysis patients, fibrates may be considered in rare cases of markedly elevated triglycerides (≥1000 mg/dL) to prevent pancreatitis. 1

Critical Safety Considerations:

• Fenofibrate is contraindicated in individuals with eGFR <30 mL/min/1.73 m² 1.
• There are limited data about the safety of gemfibrozil in patients with advanced CKD 1.
• Fibrates were associated with an acute reduction in eGFR in meta-analyses 1.
• The concurrent use of statins and fibrates raises the risk for rhabdomyolysis, and the combination should not be used in CKD 1.

Evidence from Dialysis-Specific Studies:

• Low-dose fenofibrate (100 mg per hemodialysis day) was safe and effective in reducing triglycerides in chronic hemodialysis patients with mild hypertriglyceridemia in a small double-blind crossover study 3.
• The treatment was well tolerated with no side effects, though there was a small but significant increase in creatine kinase not exceeding the upper limit of normal 3.
• If fibrates are used, dosing adjustments for kidney function are essential to avoid myalgia and other complications 1.

Common Pitfalls to Avoid

Do not automatically initiate statins or fibrates in dialysis patients based on triglyceride levels alone, as this contradicts guideline recommendations and lacks evidence for benefit 1.

Do not overlook secondary causes, particularly uncontrolled diabetes, as optimizing glycemic control can dramatically reduce triglycerides independent of lipid medications 2.

Do not use standard fibrate dosing in dialysis patients without appropriate dose adjustment for renal function 1, 4.

Do not combine statins with fibrates in dialysis patients due to significantly increased risk of rhabdomyolysis 1.

Do not ignore the risk of pancreatitis when triglycerides exceed 500 mg/dL, as this may be the only scenario where pharmacotherapy outweighs the lack of cardiovascular benefit evidence in dialysis patients 1.