Comprehensive metabolomic profiling in early IgA nephropathy patients reveals urine glycine as a prognostic biomarker

被引:19
作者
Park, Sehoon [1 ,2 ]
Lee, Jueun [3 ]
Yang, Seung Hee [4 ]
Lee, Hajeong [3 ]
Kim, Joo Young [4 ]
Park, Minkyoung [4 ]
Kim, Kyu Hong [4 ]
Moon, Jong Joo [5 ]
Cho, Semin [5 ]
Lee, Soojin [5 ]
Kim, Yaerim [6 ]
Lee, Jung Pyo [5 ,7 ]
Jeong, Chang Wook [4 ,7 ,8 ]
Kwak, Cheol [9 ]
Joo, Kwon Wook [4 ,5 ,7 ]
Lim, Chun Soo [4 ,5 ,8 ]
Kim, Yon Su [1 ,4 ,5 ,7 ]
Hwang, Geum-Sook [3 ,10 ]
Kim, Dong Ki [4 ,5 ,7 ]
机构
[1] Seoul Natl Univ, Dept Biomed Sci, Coll Med, Seoul, South Korea
[2] Armed Forces Capital Hosp, Dept Internal Med, Gyeonggi Do, South Korea
[3] Korea Basic Sci Inst, Western Seoul Ctr, Integrated Metabol Res Grp, Seoul 03759, South Korea
[4] Seoul Natl Univ, Kidney Res Inst, Seoul, South Korea
[5] Seoul Natl Univ Hosp, Dept Internal Med, Seoul, South Korea
[6] Keimyung Univ, Dept Internal Med, Sch Med, Daegu, South Korea
[7] Seoul Natl Univ, Dept Internal Med, Coll Med, 101 Daehak Ro, Seoul 03080, South Korea
[8] Seoul Natl Univ, Dept Internal Med, Boramae Med Ctr, Seoul, South Korea
[9] Seoul Natl Univ Hosp, Dept Urol, Seoul, South Korea
[10] Ewha Womans Univ, Dept Chem & Nano Sci, Seoul, South Korea
关键词
glomerulonephritis; glycine; IgA nephropathy; metabolomics; prognosis;
D O I
10.1111/jcmm.16520
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Identification of a urinary metabolite biomarker with diagnostic or prognostic significance for early immunoglobulin A nephropathy (IgAN) is needed. We performed nuclear magnetic resonance-based metabolomic profiling and identified 26 metabolites in urine samples. We collected urine samples from 201, 77, 47, 36 and 136 patients with IgAN, patients with membranous nephropathy, patients with minimal change disease, patients with lupus nephritis and healthy controls, respectively. We determined whether a metabolite level is associated with the prognosis of IgAN through Cox regression and continuous net reclassification improvement (cNRI). Finally, in vitro experiments with human kidney tubular epithelial cells (hTECs) were performed for experimental validation. As the results, the urinary glycine level was higher in the IgAN group than the control groups. A higher urinary glycine level was associated with lower risk of eGFR 30% decline in IgAN patients. The addition of glycine to a predictive model including clinicopathologic information significantly improved the predictive power for the prognosis of IgAN [cNRI 0.72 (0.28-0.82)]. In hTECs, the addition of glycine ameliorated inflammatory signals induced by tumour necrosis factor-alpha. Our study demonstrates that urinary glycine may have diagnostic and prognostic value for IgAN and indicates that urinary glycine is a protective biomarker for IgAN.
引用
收藏
页码:5177 / 5190
页数:14
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