PMID- 37736814 OWN - NLM STAT- MEDLINE DCOM- 20231204 LR - 20231217 IS - 1438-2199 (Electronic) IS - 0939-4451 (Print) IS - 0939-4451 (Linking) VI - 55 IP - 11 DP - 2023 Nov TI - Metabolomic profiling of amino acids study reveals a distinct diagnostic model for diabetic kidney disease. PG - 1563-1572 LID - 10.1007/s00726-023-03330-0 [doi] AB - Diabetic kidney disease (DKD), a highly prevalent complication of diabetes mellitus, is a major cause of mortality in patients. However, identifying circulatory markers to diagnose DKD requires a thorough understanding of the metabolic mechanisms of DKD. In this study, we performed ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to reveal altered metabolic profiles of amino acids (AAs) in patients with DKD. We found decreased plasma levels of histidine and valine, increased urine levels of proline, decreased urine levels of histidine and valine, and increased saliva levels of arginine in patients with DKD compared with the levels in patients with type 2 diabetes mellitus (T2DM) and in healthy controls. Our analyses of the key metabolites and metabolic enzymes involved in histidine and valine metabolism indicated that the AAs level alterations may be due to enhanced carnosine hydrolysis, decreased degradation of homocarnosine and anserine, enhanced histidine methylation, and systemic enhancement of valine metabolism in patients with DKD. Notably, we generated a distinct diagnostic model with an AUC of 0.957 and an accuracy up to 92.2% on the basis of the AA profiles in plasma, urine and saliva differing in patients with DKD using logistic regression and receiver operating characteristic analyses. In conclusion, our results suggest that altered AA metabolic profiles are associated with the progression of DKD. Our DKD diagnostic model on the basis of AA levels in plasma, urine, and saliva may provide a theoretical basis for innovative strategies to diagnose DKD that may replace cumbersome kidney biopsies. CI - (c) 2023. The Author(s). FAU - Wang, Jiao AU - Wang J AD - Department of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China. AD - Research Institute of Nephrology, Zhengzhou University, Zhengzhou, 450000, China. AD - Henan Province Research Center For Kidney Disease, Zhengzhou, 450000, China. FAU - Zhou, Chunyu AU - Zhou C AD - Research Institute of Nephrology, Zhengzhou University, Zhengzhou, 450000, China. AD - Henan Province Research Center For Kidney Disease, Zhengzhou, 450000, China. AD - Blood Purification Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China. FAU - Zhang, Qing AU - Zhang Q AD - Research Institute of Nephrology, Zhengzhou University, Zhengzhou, 450000, China. aquamarine61@163.com. AD - Henan Province Research Center For Kidney Disease, Zhengzhou, 450000, China. aquamarine61@163.com. FAU - Liu, Zhangsuo AU - Liu Z AD - Research Institute of Nephrology, Zhengzhou University, Zhengzhou, 450000, China. zhangsuoliu@zzu.edu.cn. AD - Henan Province Research Center For Kidney Disease, Zhengzhou, 450000, China. zhangsuoliu@zzu.edu.cn. AD - Blood Purification Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China. zhangsuoliu@zzu.edu.cn. AD - Traditional Chinese Medicine Integrated Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China. zhangsuoliu@zzu.edu.cn. LA - eng GR - 222300420345/Natural Science Foundation of Henan Province/ GR - 222300420343/Natural Science Foundation of Henan Province/ GR - LHGJ20200328/Henan Medical Science and Technology Research Program Joint Construction Project/ GR - LHGJ20200290/Henan Medical Science and Technology Research Program Joint Construction Project/ GR - SBGJ202103080/Henan Medical Science and Technique Foundation/ PT - Journal Article DEP - 20230922 PL - Austria TA - Amino Acids JT - Amino acids JID - 9200312 RN - 0 (Amino Acids) RN - 4QD397987E (Histidine) RN - 0 (Amines) RN - HG18B9YRS7 (Valine) SB - IM MH - Humans MH - *Diabetic Nephropathies/metabolism MH - Amino Acids MH - *Diabetes Mellitus, Type 2/metabolism MH - Histidine MH - Chromatography, Liquid MH - Tandem Mass Spectrometry MH - Amines MH - Valine PMC - PMC10689543 OTO - NOTNLM OT - Amino acids OT - Diabetic kidney disease OT - Diagnostic model OT - LC-MS/MS OT - Metabolomics COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/09/22 12:43 MHDA- 2023/12/04 12:42 PMCR- 2023/09/22 CRDT- 2023/09/22 06:28 PHST- 2023/07/17 00:00 [received] PHST- 2023/08/30 00:00 [accepted] PHST- 2023/12/04 12:42 [medline] PHST- 2023/09/22 12:43 [pubmed] PHST- 2023/09/22 06:28 [entrez] PHST- 2023/09/22 00:00 [pmc-release] AID - 10.1007/s00726-023-03330-0 [pii] AID - 3330 [pii] AID - 10.1007/s00726-023-03330-0 [doi] PST - ppublish SO - Amino Acids. 2023 Nov;55(11):1563-1572. doi: 10.1007/s00726-023-03330-0. Epub 2023 Sep 22.