Sources and Metabolism of D-Amino Acids and Their Roles as Biomarkers in Kidney Disease: A Review.

The human body acquires D-amino acids from multiple sources, with intestinal microbiota being the most significant contributor, followed by dietary intake and limited synthesis within the nervous system. Microbiota-derived D-amino acids can either be excreted directly in feces or absorbed into the systemic circulation, thereby influencing host metabolism and immune responses. Dietary intake, particularly from fermented or processed foods, also contributes to circulating levels of D-amino acids. With advances in analytical methodologies such as chiral chromatography and high-resolution mass spectrometry, it is now possible to detect trace concentrations of D-amino acids in plasma, urine, and tissue samples, allowing their clinical relevance to be more fully appreciated. The kidney plays a critical role in regulating systemic D-amino acid balance, as it exhibits stereoselective handling by actively reabsorbing some and excreting others into urine. This selective regulation means that alterations in D-amino acid profiles can provide valuable insight into renal physiology and pathophysiology. Clinical studies have demonstrated that specific D-amino acid patterns, including increased fractional excretion of D-serine, are associated with diseases such as diabetic nephropathy, IgA nephropathy, and chronic kidney disease. Beyond serving as biomarkers, emerging evidence suggests that D-amino acids directly influence renal outcomes: excessive D-serine has been shown to cause tubular injury, while other microbiota-derived D-amino acids may modulate immunity or confer protection in acute kidney injury. This review aims to summarize the sources and metabolism of D-amino acids and their roles as biomarkers in kidney disease.