What are the symptoms of vitamin B6 (pyridoxine) deficiency in patients with end-stage renal disease undergoing chronic hemodialysis?

Vitamin B6 Deficiency Symptoms in End-Stage Renal Disease Patients on Hemodialysis

Vitamin B6 deficiency in hemodialysis patients manifests with symptoms that overlap significantly with uremia itself, making clinical recognition challenging—the key is that deficiency presents with multiorgan system manifestations similar to uremic symptoms, including neurological dysfunction, anemia, and immune impairment. 1

Clinical Manifestations

The symptoms of vitamin B6 deficiency in dialysis patients are particularly difficult to distinguish from uremia because they affect the same organ systems:

• Neurological symptoms are prominent, as pyridoxal-5-phosphate (the active form) is essential for neurotransmitter synthesis 1
• Hematologic abnormalities occur because vitamin B6 is critical for hemoglobin synthesis, and deficiency can worsen anemia beyond what is expected from renal disease alone 1
• Immune dysfunction develops with decreased cellular immunity parameters, which can be improved with supplementation 2
• General uremic symptoms including nausea, vomiting, and appetite suppression may be exacerbated by concurrent vitamin B6 deficiency, though these are primarily driven by inadequate dialysis clearance 3

Prevalence and Risk Factors

The deficiency is extremely common in this population:

• 35.1% of chronic hemodialysis patients have documented vitamin B6 deficiency 4
• All patients develop subnormal plasma pyridoxal-5-phosphate levels when dietary intake is limited to 1.3 mg/day without supplementation, with seven of eleven patients developing severe deficiency (≤20 nmol/L) 5
• 67% of pediatric dialysis patients consume less than the RDA for vitamin B6 4, 6

Contributing Factors

Multiple mechanisms drive deficiency in hemodialysis patients:

• Dialysis losses: Hemodialysis removes vitamin B6, though peritoneal losses are relatively small (8 nmol PLP/day) 5
• Low dietary intake: Protein restriction and uremic anorexia limit vitamin B6 consumption 4, 6
• Medication interactions: Various medications interfere with pyridoxine and folate metabolism 4, 6
• Increased utilization: Erythropoietin therapy dramatically increases vitamin B6 consumption for hemoglobin synthesis 1
• Furosemide effect: Intravenous furosemide increases urinary excretion and fractional excretion of vitamin B6 1

Diagnostic Approach

Plasma pyridoxal-5-phosphate measured by HPLC is the preferred diagnostic test, with normal values ranging from 40-60 nmol/L 4, 5:

• Severe deficiency: ≤20 nmol/L 5
• Deficiency: <40 nmol/L 5
• Alternative testing: Erythrocyte glutamic pyruvic transaminase (EGPT) activity with and without added pyridoxal-5-phosphate can assess functional deficiency, with an elevated EGPT index indicating deficiency 7

Important Caveat

Plasma total vitamin B6 levels (which include non-PLP forms) may be normal even when plasma PLP is severely deficient, making PLP-specific measurement essential 5

Prevention and Treatment

The KDOQI guidelines recommend 10 mg daily pyridoxine-HCl for adult hemodialysis patients to correct documented deficiency 4, 6:

• Standard supplementation: 10 mg/day pyridoxine-HCl rapidly corrects abnormal EGPT index and maintains normal values in hemodialysis patients 7
• Lower doses are inadequate: Supplements of 5 mg/day or less often fail to maintain normal status, particularly during sepsis or when taking pyridoxine antagonists 7
• With erythropoietin therapy: 20 mg/day is recommended due to increased consumption for hemoglobin synthesis 1
• During peritonitis or sepsis: 10 mg/day may be necessary even for peritoneal dialysis patients who typically require lower doses 7

Monitoring During Treatment

The ESPEN guidelines emphasize that supplementation should be guided by serum levels and dialysis losses, as water-soluble vitamins require special attention with increased requirements during kidney failure and large effluent losses during kidney replacement therapy 4

Common Pitfalls

• Assuming normal total vitamin B6 means adequate status: Always measure plasma PLP specifically, not just total vitamin B6 5
• Attributing all symptoms to uremia: While nausea and uremic symptoms are primarily from inadequate dialysis, vitamin B6 deficiency can worsen these manifestations 3, 1
• Underdosing supplementation: 5 mg/day or less is frequently insufficient for hemodialysis patients 7
• Ignoring increased needs with EPO: Erythropoietin therapy substantially increases vitamin B6 requirements 1