Wu Henry H L, Wang Angela Yee-Moon
Department of Renal Medicine, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, United Kingdom; Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom.
Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong, China.
Vitam Horm. 2022;119:325-353. doi: 10.1016/bs.vh.2022.01.011. Epub 2022 Feb 25.
Chronic Kidney Disease (CKD) is an emerging public health issue with a fast-growing global prevalence. Impairment in vitamin B12 metabolism is considered a nontraditional risk factor of poor outcomes associated with CKD, and there is greater interest from the scientific community than ever before to explore the role and influence of vitamin B12 in CKD. Homocysteine metabolism forms an important component of the vitamin B12 metabolic pathway. Hyperhomocysteinemia is frequently observed in CKD and End-Stage Kidney Disease (ESKD), but its representation as a prognostic marker for CKD outcomes is still not fully clear. This chapter reviews the vitamin B12 and homocysteine metabolic pathways and their dysfunction in CKD states. Biochemical factors and the MTHFR genetic polymorphisms which disrupt vitamin B12 and homocysteine metabolism are explored. The mechanisms of homocysteine-mediated and vitamin B12-mediated tissue damage in CKD are discussed. This chapter reviews current perspective on definition and measurement of plasma vitamin B12 levels in the CKD population. Updated evidence investigating the prognostic role of vitamin B12 for CKD outcomes is presented. Findings from major clinical trials conducted relating to outcomes from multivitamin (including folic acid and vitamin B12) supplementation in nondialysis and dialysis-dependent CKD are highlighted. The prognostic value of vitamin B12 and effects of vitamin B12 supplementation in the context of kidney transplantation and acute kidney injury is also reviewed. Future research considerations are summarized based on evidence gaps in our knowledge base of this topic. Greater abundance of high-level evidence to guide an approach toward vitamin B12 measurement, monitoring and supplementation in CKD may contribute to improved clinical outcomes.
慢性肾脏病（CKD）是一个新出现的公共卫生问题，其全球患病率正在迅速上升。维生素B12代谢受损被认为是与CKD相关的不良结局的非传统危险因素，科学界对探索维生素B12在CKD中的作用和影响的兴趣比以往任何时候都更大。同型半胱氨酸代谢是维生素B12代谢途径的重要组成部分。高同型半胱氨酸血症在CKD和终末期肾病（ESKD）中经常观察到，但其作为CKD结局的预后标志物的表现仍不完全清楚。本章回顾了维生素B12和同型半胱氨酸代谢途径及其在CKD状态下的功能障碍。探讨了破坏维生素B12和同型半胱氨酸代谢的生化因素和MTHFR基因多态性。讨论了同型半胱氨酸介导和维生素B12介导的CKD组织损伤机制。本章回顾了当前关于CKD人群血浆维生素B12水平定义和测量的观点。介绍了关于维生素B12对CKD结局预后作用的最新研究证据。重点介绍了在非透析和依赖透析的CKD中进行的与多种维生素（包括叶酸和维生素B12）补充结局相关的主要临床试验结果。还回顾了维生素B12在肾移植和急性肾损伤背景下的预后价值和补充维生素B12的效果。基于我们在该主题知识库中的证据空白，总结了未来的研究考虑因素。更多丰富的高级证据来指导CKD中维生素B12测量、监测和补充的方法可能有助于改善临床结局。
