Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China,
Department of Nephrology, Kiang Wu Hospital, Macau, China.
Kidney Blood Press Res. 2023;48(1):287-296. doi: 10.1159/000530209. Epub 2023 Apr 10.
The glomerular filtration rate (GFR) is crucial for chronic kidney disease (CKD) diagnosis and therapy. Various studies have sought to recognize ideal endogenous markers to improve the estimated GFR for clinical practice. To screen out potential novel metabolites related to GFR (mGFR) measurement in CKD patients from the Chinese population, we identified more biomarkers for improving GFR estimation.
Fifty-three CKD participants were recruited from the Third Affiliated Hospital of Sun Yat-sen University in 2020. For each participant, mGFR was evaluated by utilizing the plasma clearance of iohexol and collecting serum samples for untargeted metabolomics analyses by ultrahigh-performance liquid chromatography-tandem mass spectroscopy. All participants were divided into four groups according to mGFR. The metabolite peak area data were uploaded to MetaboAnalyst 5.0 for one-way analysis of variance, principal component analysis, and partial least squares-discriminant analysis and confirmed the metabolites whose levels increased or decreased with mGFR and variable importance in projection (VIP) values >1. Metabolites were ranked by correlation with the original values of mGFR, and metabolites with a correlation coefficient >0.8 and VIP >2 were identified.
We screened out 198 metabolites that increased or decreased with mGFR decline. After ranking by correlation with mGFR, the top 50 metabolites were confirmed. Further studies confirmed the 10 most highly correlated metabolites.
We screened out the metabolites that increased or decreased with mGFR decline in CKD patients from the Chinese population, and 10 of them were highly correlated. They are potential novel metabolites to improve GFR estimation.
肾小球滤过率(GFR)对慢性肾脏病(CKD)的诊断和治疗至关重要。多项研究试图寻找理想的内源性标志物,以改善估算的 GFR 用于临床实践。为了从中国人群中筛选出与 CKD 患者 mGFR 测量相关的潜在新型代谢物,我们确定了更多用于改善 GFR 估算的生物标志物。
2020 年,中山大学附属第三医院招募了 53 名 CKD 参与者。对于每个参与者,通过利用 iohexol 的血浆清除率评估 mGFR,并收集血清样本,通过超高效液相色谱-串联质谱法进行非靶向代谢组学分析。所有参与者根据 mGFR 分为四组。将代谢物峰面积数据上传至 MetaboAnalyst 5.0,进行单因素方差分析、主成分分析和偏最小二乘判别分析,并确认与 mGFR 呈正相关或负相关的代谢物及其 VIP 值 >1。按与 mGFR 原始值的相关性对代谢物进行排序,确定与原始 mGFR 值相关性 >0.8 和 VIP >2 的代谢物。
我们筛选出了 198 种随 mGFR 下降而增加或减少的代谢物。根据与 mGFR 的相关性进行排序后,确认了前 50 种代谢物。进一步的研究证实了与 mGFR 相关性最高的 10 种代谢物。
我们从中国人群中筛选出与 CKD 患者 mGFR 下降相关的增加或减少的代谢物,其中 10 种代谢物与 mGFR 高度相关。它们是潜在的新型代谢物,可改善 GFR 估算。