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.

Intra-body dynamics of d-serine reflects the origin of kidney diseases

“…Because FE of l- serine is usually well conserved and less affected than that of d- serine by kidney tubular injury [ 7 ], an increased FE of l- serine may be an overlooked factor that can distinguish DN. The dynamics of d -serine was balanced by such factors as food intake, synthesis through a racemic reaction in brain [ 20 ] and by gut microbiota [ 21 , 22 ], and urinary excretion [ 7 , 9 ]. On the other hand, the blood level of d -serine is well regulated by the kidney through the adjustment of urinary excretion, and this feature is the key for the strong correlation with GFR [ 7 , 9 ].…”

“…The dynamics of d -serine was balanced by such factors as food intake, synthesis through a racemic reaction in brain [ 20 ] and by gut microbiota [ 21 , 22 ], and urinary excretion [ 7 , 9 ]. On the other hand, the blood level of d -serine is well regulated by the kidney through the adjustment of urinary excretion, and this feature is the key for the strong correlation with GFR [ 7 , 9 ]. In the presence of kidney diseases, however, the correlation between d -serine and eGFR became weaker, because of the disturbance in the regulation of d -serine dynamics.…”

“…d-Serine is now emerging as a biomarker of kidney diseases [6][7][8][9]. d-Serine, one of the d-amino acids, is a mirrorimaged enantiomer (chiral body) of serine that is present only in trace amounts in nature unlike abundant l-serine [10,11].…”

Subchronic Tolerance Trials of Graded Oral Supplementation with Phenylalanine or Serine in Healthy Adults

“…Finally, serine can also be diverted to its enantiomer (D-serine). Yet, because serine racemase, which catalyzes the stereochemical inversion of serine to D-serine, is present mainly in the brain [29], we hypothesized that serine supplementation would not have resulted in an increased circulating D-serine, and we did not evaluate it.…”

Advances in D-Amino Acids in Neurological Research

“…As all four of these amino acids modulate the NMDA receptor, there has been significant interest in their regulation, which will be discussed in detail later in this review. The primary method for eliminating D-amino acids is that they are transported to the kidneys and metabolized before being excreted [ 93 , 94 , 95 ]. While both DAAO and DDO are expressed in the brain, the highest levels of expression for DAAO are in the liver and kidneys, and the highest level of expression for DDO is in the heart [ 28 , 96 ].…”