D-Amino acids and kidney diseases

Abstract

D-Amino acids are the recently detected enantiomers of L-amino acids. Accumulating evidence points their potential in solving the long-standing critical problems associated with the management of both chronic and acute kidney diseases. This includes estimating kidney function, early diagnosis and prognosis of chronic kidney disease, and disease monitoring. Among the D-amino acids, D-serine levels in the blood are strongly correlated with the glomerular filtration rate and are useful for estimating the function of the kidney. Urinary D-serine also reflects other conditions. The kidney proximal tubule reabsorbs serine with chiral-selectivity, with D-serine being reabsorbed much less efficiently than L-serine, and urinary excretion of D-serine is sensitive to the presence of kidney diseases. Therefore, assessing the intra-body dynamics of D-serine by measuring its level in blood and urinary excretion can be used to detect kidney diseases and assess pathophysiology. This new concept, the intra-body dynamics of D-serine, can be useful in the comprehensive management of kidney disease.

Keywords: Biomarker; D-Amino acids; D-Serine; Early screening; Glomerular filtration rate; Kidney disease; Prognosis.

Fig. 1

d-Amino acids and kidney disease. a Each amino acid, except glycine, has a chiral center and consists of two enantiomers, l- and d-amino acids. b Monitoring d-amino acids enables comprehensive management of kidney diseases, from early detection, assessment of kidney function, monitoring disease activity, and prediction of prognosis

Fig. 2

Monitoring intra-body dynamics of d-serine for assessment of the kidney diseases activity. a Higher blood levels of d-serine are associated with worse prognosis of patients with CKD. Note that this trend is chiral-selective and is not observed in l-serine. b Blood levels of d-serine are well correlated with inulin clearance, the golden standard for glomerular filtration rate, a key feature in predicting GFR. This correlation is compatible with that of creatinine. LN log-natural transformed. c In the recovery phase of a patient with acutely worsened kidney, blood levels of d-serine dynamically responded to treatment. This trend paralleled the changes in blood creatinine. d Plotting of intra-body dynamics of d-serine indexed by plasma levels and fractional excretions (FE). The profile of non-CKD conditions has been represented to be restricted within a certain range (dotted eclipse, 95% CI), whereas that of CKD condition has been represented to be broad and mostly outside the eclipse. The profile shifts from 1 to 6 in the recovery course of acutely worsened kidney. Figures are adopted from references [–5] with modifications

Fig. 3

Regulation of intra-body dynamics of d-amino acids by the kidneys. d-Amino acids, either orally consumed or produced by serine racemase in case of d-serine, are delivered to the kidneys. Filtrated d-amino acids by the kidneys are either excreted via urine or reabsorbed to re-enter blood circulation. Images are modified from Servier Medical Art, licensed under a Creative Commons Attribution 3.0 Generic License. https://smart.servier.com/