Should folate be routinely supplemented in dialysis (renal replacement therapy) patients?

Folate Supplementation in Dialysis Patients

Folate should not be routinely supplemented in dialysis patients unless there is documented folate deficiency or insufficiency based on clinical signs and symptoms. 1

Evidence-Based Approach to Folate Supplementation

Current Guidelines on Folate Supplementation

The 2020 KDOQI Clinical Practice Guideline for Nutrition in CKD provides clear recommendations against routine folate supplementation in dialysis patients:

• For adults with CKD 3-5D or post-transplantation who have hyperhomocysteinemia associated with kidney disease, folate supplementation is not recommended routinely since there is no evidence demonstrating reduction in adverse cardiovascular outcomes (Level 1A evidence) 1

• Folate, vitamin B12, and/or B-complex supplements should only be prescribed to correct for folate or vitamin B12 deficiency/insufficiency based on clinical signs and symptoms (Level 2B evidence) 1

Assessment of Folate Status

To determine if folate supplementation is needed:

1. Measure folate status in patients with:

   • Macrocytic anemia
   • Risk of malnutrition
   • Hyporesponsiveness to erythropoietin therapy 1, 2

2. Use appropriate testing:

   • Red blood cell (RBC) folate provides a more accurate assessment of tissue folate stores than serum folate 2
   • Serum folate reflects recent intake rather than tissue stores 1

When Folate Supplementation Is Indicated

Folate supplementation should be provided in these specific situations:

1. Documented folate deficiency based on:

   • Low RBC folate levels
   • Clinical signs (macrocytosis, hypersegmented neutrophils) 2

2. High-risk patients:

   • Malnourished patients
   • History of alcohol abuse
   • Patients on high-flux/high-efficiency dialysis 3
   • Patients with poor dietary intake 1

3. Dosing recommendations when indicated:

   • For deficiency: 1-5 mg/day orally 1, 4
   • For patients on high-flux dialysis: 1 mg after each dialysis session may be sufficient 4, 3

Evidence Against Routine Supplementation

Several studies demonstrate that routine folate supplementation is unnecessary:

• A study of 41 hemodialysis patients showed that after stopping folate supplementation (5 mg/day), no patient developed folate deficiency over 16 months when consuming adequate protein (60-80g/day) 5

• Another study found surprisingly low incidence of true folate deficiency in both peritoneal dialysis (0%) and hemodialysis patients (10%) even without supplementation 6

• Dietary intake of 60g protein/day typically provides sufficient folate to balance dialysis losses 2

Special Considerations

Folate for Hyperhomocysteinemia

• High-dose folate (5-15 mg/day) can reduce plasma homocysteine levels by 25-30% 2
• However, this reduction has not been shown to improve cardiovascular outcomes 1
• If treating hyperhomocysteinemia, ensure adequate vitamin B12 status before initiating high-dose folate 7

Monitoring Recommendations

• If supplementation is initiated, recheck folate status within 3 months to verify normalization 1
• For patients on high-flux dialysis membranes, more frequent monitoring may be needed as these can increase folate losses 3

Practical Algorithm for Folate Management in Dialysis Patients

1. Assess risk factors for folate deficiency:

   • Poor nutritional status
   • High-flux dialysis
   • Macrocytic anemia
   • Erythropoietin resistance

2. Measure RBC folate levels in at-risk patients

3. If deficient: Supplement with 1-5 mg folate daily or 1 mg after each dialysis session

4. If normal: Routine supplementation is not necessary; encourage adequate dietary intake

5. Monitor response to supplementation after 3 months

In conclusion, the evidence strongly suggests that folate supplementation should be targeted rather than routine in dialysis patients, focusing on those with documented deficiency or specific risk factors.