Urine metabolomics reveals biomarkers and the underlying pathogenesis of diabetic kidney disease

Luo, Maolin1,2; Zhang, Zeyu1,3; Lu, Yongping1; Feng, Weifeng4; Wu, Hongwei1; Fan, Lijing1; Guan, Baozhang1; Dai, Yong3; Tang, Donge3; Dong, Xiangnan1; Yun, Chen5; Hocher, Berthold1,5,6; Liu, Haiping7; Li, Qiang8; Yin, Lianghong1

2022-10-01

10.1007/s11255-022-03326-x

INTERNATIONAL UROLOGY AND NEPHROLOGY   Impact Factor & Quartile

0301-1623

1573-2584

Purpose Diabetic kidney disease (DKD) is the most common complication of type 2 diabetes mellitus (T2DM), and its pathogenesis is not yet fully understood and lacks noninvasive and effective diagnostic biomarkers. In this study, we performed urine metabolomics to identify biomarkers for DKD and to clarify the potential mechanisms associated with disease progression. Methods We applied a liquid chromatography-mass spectrometry-based metabolomics method combined with bioinformatics analysis to investigate the urine metabolism characteristics of 79 participants, including healthy subjects (n = 20), T2DM patients (n = 20), 39 DKD patients that included 19 DKD with microalbuminuria (DKD + micro) and 20 DKD with macroalbuminuria (DKD + macro). Results Seventeen metabolites were identified between T2DM and DKD that were involved in amino acid, purine, nucleotide and primarily bile acid metabolism. Ultimately, a combined model consisting of 2 metabolites (tyramine and phenylalanylproline) was established, which had optimal diagnostic performance (area under the curve (AUC) = 0.94). We also identified 19 metabolites that were co-expressed within the DKD groups and 41 metabolites specifically expressed in the DKD + macro group. Ingenuity pathway analysis revealed three interaction networks of these 60 metabolites, involving the sirtuin signaling pathway and ferroptosis signaling pathway, as well as the downregulation of organic anion transporter 1, which may be important mechanisms that mediate the progression of DKD. Conclusions This work reveals the metabolic alterations in T2DM and DKD, constructs a combined model to distinguish them and delivers a novel strategy for studying the underlying mechanism and treatment of DKD.

Diabetic kidney disease Metabolomics Ingenuity pathway analysis Sirtuin signaling Ferroptosis OAT1

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English

Others

Guangdong Province Blood Depuration Clinical Engineering Technology Research Center[507204531040] ; 2019 Dongguan Social Science and Technology Development (key) project[201950715002195] ; Guangdong Province Union Training Postgraduate Demonstration base[20190630] ; Guangdong Science and Technology Projects[2020A1313030112] ; Guangzhou International Conference capital construction project[X20210101] ; Postdoctoral Fund of the First Affiliated Hospital, Jinan University[809001] ; Young Innovative Talents Project of General Colleges and Universities in Guangdong Province[2018KQNCX010] ; GuangDong Basic and Applied Basic Research Foundation[2020A1515111209] ; Key Diabetes Specialty Construction of Liwan District People's Hospital[201804001]

Urology & Nephrology

Urology & Nephrology

WOS:000869635700001

SPRINGER

CLINICAL MEDICINE

Web of Science

1.Jinan Univ, Affiliated Hosp 1, Dept Nephrol & Blood Purificat, Guangzhou 510632, Peoples R China
2.Peoples Hosp Liwan Dist, Dept Endocrinol & Metab, Guangzhou 510380, Peoples R China
3.Jinan Univ, Southern Univ Sci & Technol, Clin Med Coll 2, Shenzhen Peoples Hosp,Affiliated Hosp 1, Shenzhen 518020, Peoples R China
4.Jinan Univ, Affiliated Hosp 1, Dept Tradit Chinese Med, Guangzhou 510632, Peoples R China
5.Charite Univ Med Berlin, Campus Mitte, Dept Nephrol, Berlin, Germany
6.Univ Med Ctr Mannheim, Dept Med Nephrol, Heidelberg, Germany
7.Second Peoples Hosp Lianping Cty, Heyuan 517139, Guangdong, Peoples R China
8.Guangzhou Univ Tradit Chinese Med, Dongguan Hosp, Guangzhou 523000, Guangdong, Peoples R China

Luo, Maolin,Zhang, Zeyu,Lu, Yongping,et al. Urine metabolomics reveals biomarkers and the underlying pathogenesis of diabetic kidney disease[J]. INTERNATIONAL UROLOGY AND NEPHROLOGY,2022.

Luo, Maolin.,Zhang, Zeyu.,Lu, Yongping.,Feng, Weifeng.,Wu, Hongwei.,...&Yin, Lianghong.(2022).Urine metabolomics reveals biomarkers and the underlying pathogenesis of diabetic kidney disease.INTERNATIONAL UROLOGY AND NEPHROLOGY.

Luo, Maolin,et al."Urine metabolomics reveals biomarkers and the underlying pathogenesis of diabetic kidney disease".INTERNATIONAL UROLOGY AND NEPHROLOGY (2022).