CHAPTER 47: Cobalamin and Nutritional Implications in Kidney Disease

This chapter primarily describes how the metabolism of vitamin B₁₂ is influenced by the progression of chronic kidney disease (CKD), i.e. decreased kidney function, and what happens subsequently in the biological process. Vitamin B₁₂ must be converted into its coenzyme forms, adenosylcobalamin and methylcobalamin, in the cell. These coenzymes function as the cofactors of methylmalonyl-CoA mutase and methionine synthase, respectively. CKD may affect the conversion from vitamin B₁₂ to the coenzyme forms and this may be why CKD induces vitamin B₁₂ deficiency by reducing the availability of this coenzyme. The best known biomarker associated with vitamin B₁₂ is homocysteine. Given that homocysteine metabolism is involved both in the synthesis and degradation of asymmetric dimethylarginine (ADMA), a potent endogenous NO-synthase inhibitor which is thought to be an independent predictor of cardiovascular mortality in end-stage renal disease, homocysteine management is clinically important in CKD patients. Since human vascular cells lack cystathionine beta-synthase, vascular endothelium may be extremely vulnerable to homocysteine loading induced by impaired remethylation. Thus homocysteine metabolism disorder should not be ignored in these patients. When vitamin B₁₂ and vitamin B₆ are viewed in terms of homocysteine metabolism, both vitamins may be linked with each other in the degradation of homocysteine.