Abstract
D-Amino acids, long-term undetected enantiomers of L-amino acids, are now emerging as potential biomarkers, especially for kidney diseases. Management of chronic kidney disease (CKD), a global problem with its high prevalence and poor prognosis, is currently unsatisfactory due to the difficulty in estimating kidney function and in early detection of diseases. We now show that intra-body dynamics of D-serine reflect kidney function and diseases. The blood level of D-serine correlated well with the actual glomerular filtration ratio, a key kidney function. This correlation was compatible with those of conventional kidney markers, and blood level of D-serine was relatively unaffected by such clinical factors as body size. The balance between excretion and reabsorption of amino acids by the kidney was controlled with chiral selectivity, and the reabsorption of D-serine was sensitive to the presence of CKD. The combination of blood level and urinary dynamics of D-serine effectively distinguished CKD from non-CKD. These lines of evidence provide new insights into the enantioselective amino acid dynamics in the human body that reflect disease pathophysiology. D-Serine may serve as a vital biomarker that suppress CKD onset through the precise assessment of kidney function and the diagnosis of CKD.
Highlights
Ever since the discovery of D-amino acid oxidase in the kidney[1], the physiological and pathological functions of D-amino acids in the human body have not been fully elucidated[2]
In order to examine the relationship between glomerular filtration ratio (GFR) and chiral amino acids, we measured inulin clearance, the golden standard for GFR, and simultaneously performed chiral amino metabolomics[10,11]
This study demonstrated the clinical utilities of chiral metabolomics, and provided a theoretical background for chiral amino acids as future biomarkers for chronic kidney disease (CKD)
Summary
Ever since the discovery of D-amino acid oxidase in the kidney[1], the physiological and pathological functions of D-amino acids in the human body have not been fully elucidated[2]. Chiral metabolomics of CKD patients revealed that trace amounts of D-amino acids do exist in human blood, and that the blood levels of chiral amino acids are associated with several clinical factors[5]. One of these close clinical relationships is the association between plasma D-serine and the creatinine-based estimated GFR (eGFR), a commonly-used surrogate marker for kidney function. Another important finding is that chiral amino acids are prognostic markers for CKD. Correspondence and requests for materials should be addressed to T.K
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