Is folic acid supplementation necessary in patients with End-Stage Renal Disease (ESRD)?

Folic Acid Supplementation in End-Stage Renal Disease (ESRD)

Folic acid supplementation should not be routinely prescribed for all ESRD patients but should be reserved for those with documented folate deficiency or insufficiency based on clinical signs and symptoms. 1

Evidence-Based Recommendations for Folic Acid in ESRD

Assessment and Indications

• The 2020 KDOQI Clinical Practice Guideline for Nutrition in CKD specifically addresses folic acid supplementation in ESRD:
  • For hyperhomocysteinemia: Not recommended for routine supplementation as there is no evidence demonstrating reduction in adverse cardiovascular outcomes (Grade 1A) 1
  • For folate deficiency/insufficiency: Supplementation is suggested based on clinical signs and symptoms (Grade 2B) 1

Dosing Recommendations

When folate deficiency is confirmed in ESRD patients:

• Daily supplementation (5 mg) appears more beneficial than weekly supplementation for reducing arteriovenous access thrombosis risk 2
• Standard multivitamin preparations containing 800 μg folic acid can reduce homocysteine levels by nearly 50%, though normalization is often not achieved 3

Monitoring

• Regular assessment of dietary vitamin intake is reasonable for ESRD patients 1
• Collaboration between registered dietitian nutritionists and physicians is recommended for periodic assessment 1

Special Considerations

Dialysis Patients with Inadequate Intake

• For ESRD patients on dialysis with inadequate dietary intake for sustained periods, multivitamin supplementation including water-soluble vitamins (including folate) may be considered 1
• Dialysis removes folate, potentially contributing to deficiency 2

Potential Benefits Beyond Homocysteine Reduction

• A large retrospective cohort study from Taiwan showed improved all-cause and cardiovascular mortality rates with folic acid supplementation in hemodialysis patients 4
• Daily 5 mg folic acid supplementation might reduce arteriovenous access thrombosis compared to weekly supplementation 2

Common Pitfalls and Caveats

1. Avoiding unnecessary supplementation: Despite the high prevalence of hyperhomocysteinemia in ESRD patients, routine supplementation for this indication alone is not recommended 1

2. Recognizing refractory hyperhomocysteinemia: Unlike in the general population, folic acid supplementation often fails to normalize homocysteine levels in ESRD patients 5, 3

3. Dosing considerations: Lower doses (800 μg) in multivitamin preparations may be as effective as higher doses for homocysteine reduction 3

4. Monitoring effectiveness: Even with supplementation, complete normalization of homocysteine levels may not occur in most ESRD patients 5

In conclusion, while folic acid supplementation has traditionally been considered for ESRD patients, current high-quality evidence from KDOQI guidelines supports a targeted approach based on documented deficiency rather than routine supplementation for all patients. When supplementation is indicated, daily administration appears to offer advantages over weekly dosing for certain outcomes.