Background: Homocysteine (Hcy) is an intermediate of methionine metabolism. Hyperhomocysteinemia (HHcy) can result from a deficiency in the enzymes or vitamin cofactors required for Hcy metabolism. Patients with renal disease tend to be hyperhomocysteinemic, particularly as renal function declines, although the underlying cause of HHcy in renal disease is not entirely understood. Summary: HHcy is considered a risk or pathogenic factor in the progression of chronic kidney disease (CKD) as well as the cardiovascular complications. Key Messages: In this review, we summarize both clinical and experimental findings that reveal the contribution of Hcy as a pathogenic factor to the development of CKD. In addition, we discuss several important mechanisms mediating the pathogenic action of Hcy in the kidney, such as local oxidative stress, endoplasmic reticulum stress, inflammation and hypomethylation.

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