ArticlePloS one2014
Ischemic acute kidney injury perturbs homeostasis of serine enantiomers in the body fluid in mice: early detection of renal dysfunction using the ratio of serine enantiomers.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 76 citations in OpenAlex.
- Application of Analytical Techniques to Chiral Amino Acid Profiling in Clinical Samples: Bridging Chemistry and Disease Research.Chirality · 2026Review
- Biomolecular and cellular chirality: Novel diagnostic perspectives for diseases.APL bioengineering · 2026Review
- Sources and Metabolism of D-Amino Acids and Their Roles as Biomarkers in Kidney Disease: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- d-amino acids: new functional insights.The FEBS journal · 2025Review
- Mammalian Tolerance to Amino Acid Heterochirality.Chembiochem : a European journal of chemical biology · 2025Review
- The Potential Mechanism of D-Amino Acids - Mitochondria Axis in the Progression of Diabetic Kidney Disease.Kidney international reports · 2025Review
- Variations of blood D-serine and D-aspartate homeostasis track psychosis stages.Schizophrenia (Heidelberg, Germany) · 2024Article
- Urinary D-amino acid profiles in cats with chronic kidney disease.The Journal of veterinary medical science · 2024Article
- Plasma D-asparagine and the D/L-serine ratio reflect chronic kidney diseases in children regardless of physique.Amino acids · 2024Article
- Article
- D-Serine as a sensor and effector of the kidney.Clinical and experimental nephrology · 2023Review
- Determination of D-serine and D-alanine Tissue Levels in the Prefrontal Cortex and Hippocampus of Rats After a Single Dose of Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, with Potential Antipsychotic and Antidepressant Properties.Neurochemical research · 2023Article
- Detection and analysis of chiral molecules as disease biomarkers.Nature reviews. Chemistry · 2023Review
- Chiral resolution of plasma amino acids reveals enantiomer-selective associations with organ functions.Amino acids · 2022Article
- Measurement of glomerular filtration rate using endogenous d-serine clearance in living kidney transplant donors and recipients.EClinicalMedicine · 2022Article
- Urinary l-erythro-β-hydroxyasparagine-a novel serine racemase inhibitor and substrate of the Zn2+-dependent d-serine dehydratase.Bioscience reports · 2021Article
- D-Serine: A Cross Species Review of Safety.Frontiers in psychiatry · 2021Review
- NMDA Receptor Hypofunction in the Aging-Associated Malfunction of Peripheral Tissue.Frontiers in physiology · 2021Article
- Exome Sequencing Identifies A Nonsense Variant in DAO Associated With Reduced Energy Expenditure in American Indians.The Journal of clinical endocrinology and metabolism · 2020Article
- Serum D-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter Asc-1.Scientific reports · 2019Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The imbalance of blood and urine amino acids in renal failure has been studied mostly without chiral separation. Although a few reports have shown the presence of D-serine, an enantiomer of L-serine, in the serum of patients with severe renal failure, it has remained uncertain how serine enantiomers are deranged in the development of renal failure. In the present study, we have monitored serine enantiomers using a two-dimensional HPLC system in the serum and urine of mice after renal ischemia-reperfusion injury (IRI), known as a mouse model of acute kidney injury. In the serum, the level of D-serine gradually increased after renal IRI in parallel with that of creatinine, whereas the L-serine level decreased sharply in the early phase after IRI. The increase of D-serine was suppressed in part by genetic inactivation of a D-serine-degrading enzyme, D-amino acid oxidase (DAO), but not by disruption of its synthetic enzyme, serine racemase, in mice. Renal DAO activity was detected exclusively in proximal tubules, and IRI reduced the number of DAO-positive tubules. On the other hand, in the urine, D-serine was excreted at a rate nearly triple that of L-serine in mice with sham operations, indicating that little D-serine was reabsorbed while most L-serine was reabsorbed in physiological conditions. IRI significantly reduced the ratio of urinary D-/L-serine from 2.82 ± 0.18 to 1.10 ± 0.26 in the early phase and kept the ratio lower than 0.5 thereafter. The urinary D-/L-serine ratio can detect renal ischemia earlier than kidney injury molecule-1 (KIM-1) or neutrophil gelatinase-associated lipocalin (NGAL) in the urine, and more sensitively than creatinine, cystatin C, or the ratio of D-/L-serine in the serum. Our findings provide a novel understanding of the imbalance of amino acids in renal failure and offer a potential new biomarker for an early detection of acute kidney injury.
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