Background: d-serine, a long-term undetected enantiomer of serine, is a biomarker that reflects kidney function and disease activity. The physiologic functions of d-serine are unclear.
Methods: The dynamics of d-serine were assessed by measuring d-serine in human samples of living kidney donors using two-dimensional high-performance liquid chromatography, and by autoradiographic studies in mice. The effects of d-serine on the kidney were examined by gene expression profiling and metabolic studies using unilateral nephrectomy mice, and genetically modified cells.
Results: Unilateral nephrectomy in human living kidney donors decreases urinary excretion and thus increases the blood level of d-serine. d-serine is quickly and dominantly distributed to the kidney on injection in mice, suggesting the kidney is a main target organ. Treatment of d-serine at a low dose promotes the enlargement of remnant kidney in mouse model. Mechanistically, d-serine activates the cell cycle for tissue remodeling through an mTOR-related pathway.
Conclusions: d-serine is a physiologic molecule that promotes kidney remodeling. Besides its function as a biomarker, d-serine has a physiologic activity that influences kidney function.
Keywords: basic science; biomarker; cell cycle; chronic kidney disease; d-serine; glomerular filtration rate; kidney remodeling; kidney transplantation; mTOR; physiological activity; renal-physiology; urinary excretion.
Copyright © 2021 by the American Society of Nephrology.