Testing the homocysteine hypothesis in end-stage renal disease: Problems and a possible solution

Area of Science:

• Cardiovascular Science
• Nephrology
• Nutritional Science

Background:

• The homocysteine hypothesis posits that elevated homocysteine levels act as a vascular toxin, relevant in both general populations and patients with renal failure.
• The Kidney and End State Renal Disease Study (HOST) was designed to test this hypothesis.

Purpose of the Study:

• To evaluate the validity of the homocysteine hypothesis in the context of end-stage renal disease.
• To identify potential confounding factors and limitations in the ongoing HOST study.
• To explore alternative therapeutic strategies for homocysteine reduction.

Main Methods:

• The study critically examines the design and potential limitations of the HOST study.
• It discusses the impact of folic acid fortification in the American food supply on the HOST's treatment efficacy.
• It raises concerns about high-dose vitamin supplementation (folic acid, pyridoxine) and reverse epidemiology confounding the HOST results.

Main Results:

• Emerging data suggest the HOST study's results may be inconclusive.
• Folic acid's therapeutic effect in the HOST may be diminished due to widespread food fortification.
• Potential confounding from high-dose vitamins and reverse epidemiology may compromise the HOST's findings.

Conclusions:

• Parenteral vitamin B12 presents a promising therapeutic approach for reducing homocysteine in end-stage renal disease patients.
• Clinical trials investigating parenteral vitamin B12 are recommended to test the homocysteine hypothesis, avoiding the limitations of the HOST study.