MTHFR and chronic kidney disease: In addition to CBS deficiency, elevated plasma Hcy can also originate from (1) genetic defects in Hcy metabolism (e.g., methylenetetrahydrofolate reductase (MTHFR) mutations impairing remethylation), (2) acquired deficiencies of vitamin cofactors (B6, B12, or folate) required for Hcy processing, or (3) secondary metabolic disturbances associated with aging or chronic kidney disease [3,4].