慢性肾脏疾病晚期患者的尿代谢组学特征分析
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摘要
目的研究尿代谢物在慢性肾脏疾病(CKD)晚期患者中的变化及与肾脏疾病发展的相关性。方法通过NMR分析15例患者和15例健康人的尿代谢组分,进行主成分分析(PCA)检验,并进一步运用液相色谱-三重四极杆质谱法分析另外16例CKD患者和15例对照的尿液样本进行验证,并鉴定CKD和非CKD尿样之间的尿代谢物。结果发现CKD和非CKD尿样之间有七种尿代谢物显著不同(P<0.05),其中枸橼酸盐、牛磺酸、5-羟脯氨酸在CKD患者中显著降低(P<0.05),而谷氨酸、鸟苷酸乙酸酯、α-苯乙酰谷氨酰胺和N-氧化三甲胺显著上升(P<0.05)。根据这些代谢物的变化趋势,5例CKD患者中有4例被鉴定为CKD患者(80%准确性),7例健康人中有6例被划分到对照区(86%准确性)。结论该方法特异度高,可以用来预测CKD,其临床引用前景良好。
Objective To study the changes of urinary metabolites in patients with advanced chronic renal disease and their correlation with the development of renal diseases.Methods In order to identify such markers as a proof of principle and determine if a metabolite signature corresponding to CKD can be found in urine.In the discovery stage,NMR was applied to determine the urine metabolome of 15 patients with CKD and compared that with the metabolome of 15 healthy individuals and found a classification pattern clearly indicative of CKD.A validation cohort of urine samples from an additional 16 patients with CKD and 15 controls was then analyzed by(Selected Reaction Monitoring)liquid chromatography-triple quadrupole mass spectrometry between CKD and non-CKD urine samples.Results The results indicated a group of seven urinary metabolites differed between CKD and non-CKD urine samples(P<0.05).Among which,citrate,taurine and 5-oxoproline(P<0.05)were significantly decreased,while glutamate,guanidoacetate,a-phenylacetylglutamine and trimethylamine N-oxide(P<0.05)were significantly increased.According to the change trend of these metabolites,four of five in patients with chronic kidney disease(CKD)had been identified as CKD(80%accuracy),six of the seven health people were divided into the control area(86% accuracy).Conclusion This method has high specificity,and can be used to predict chronic kidney disease(CKD),which has good prospects for clinical reference.
Objective To study the changes of urinary metabolites in patients with advanced chronic renal disease and their correlation with the development of renal diseases.Methods In order to identify such markers as a proof of principle and determine if a metabolite signature corresponding to CKD can be found in urine.In the discovery stage,NMR was applied to determine the urine metabolome of 15 patients with CKD and compared that with the metabolome of 15 healthy individuals and found a classification pattern clearly indicative of CKD.A validation cohort of urine samples from an additional 16 patients with CKD and 15 controls was then analyzed by(Selected Reaction Monitoring)liquid chromatography-triple quadrupole mass spectrometry between CKD and non-CKD urine samples.Results The results indicated a group of seven urinary metabolites differed between CKD and non-CKD urine samples(P<0.05).Among which,citrate,taurine and 5-oxoproline(P<0.05)were significantly decreased,while glutamate,guanidoacetate,a-phenylacetylglutamine and trimethylamine N-oxide(P<0.05)were significantly increased.According to the change trend of these metabolites,four of five in patients with chronic kidney disease(CKD)had been identified as CKD(80%accuracy),six of the seven health people were divided into the control area(86% accuracy).Conclusion This method has high specificity,and can be used to predict chronic kidney disease(CKD),which has good prospects for clinical reference.
引文
[1]DRAWZ P,AHMAN M.Chronic kidney disease[J].Annals of Internal Medicine,2015,162(11):ITC1.
[2]文集,谢席胜,张明华,等.基于创新中医理论辨证施治慢性肾脏疾病的临床研究[J].四川大学学报(医学版),2014,45(1):34-38.WEN Ji,XIE Xisheng,ZHANG Minghua,et al.Management of chronic kindney disease guided by the theory of traditional Chinese Medicine:an experimental study[J].Journal of Sichuan University(Medical Edition),2014,45(1):34-38.
[3]张晓敏,刘宏,刘必成.高尿酸血症与慢性肾脏病发生发展关系的研究进展[J].东南大学学报(医学版),2013,32(1):114-117.ZHANG Xiaomin,LIU Hong,LIU Bicheng.Progress in the relationship between hyperuricemia and the development of chronic kidney disease[J].Journal of Southeast University(Medical Edition),2013,32(1):114-117.
[4]阙凤连,肖文霞,吴一行.2型糖尿病患者内生肌酐清除率与慢性并发症的关系[J].广东医学,2014,35(13):2022-2024.QUE Fenglian,XIAO Wenxia,WU Yixing.Relationship between creatinine clearance and chronic complications in patients with type 2diabetes[J].Guangdong Medicine,2014,35(13):2022-2024.
[5]PERALYA C A,SHLIPAK M G,JUDD S,et al.Detection of chronic kidney disease with creatinine,cystatin C and urine albumin-to-creatinine ratio and association with progression to end-stage renal disease and mortality[J].the Journal of the American Medical Association,2011,305(15):1545-1552.
[6]王小丽,刘瑞东.尿TGF-β1检测在诊断慢性肾炎中的临床应用[J].现代检验医学杂志,2015,30(1):88-90.WANG Xiaoli,LIU Ruidong.Clinical application of urinary tra-nsforming growth factor-beta(TGF-β1)measurement in diagnosing chronic nephritis[J].Journal of Modern Laboratory Medicine,2015,30(1):88-90.
[7]POSADA-AYALA M,ZUBIRI I,MARTIN-LOREN-ZO M,et al.Identification of a urine metabolomic signature in patients with advanced-stage chronic kidney disease[J].Kidney International,2014,85(1):103-111.
[8]PHISITKUL S,KHANNA A,SIMONI J,et al.A-melioration of metabolic acidosis in patients with low GFR reduced kidney endothelin production and kidney injury,and better preserved GFR[J].Kidney International,2010,77(7):617-623.
[9]GAO X,CHEN W,LI R,et al.Systematic variations associated with renal disease uncovered by parallel metabolomics of urine and serum[J].BMC Systems Biology,2012,6(1):S14.
[10]QI S,OUYANG X,WANG L,et al.A pilot metabolic profiling study in serum of patients with chronic kidney disease based on 1 H-NMR-Spectroscopy[J].Clinical and Translational Science,2012,5(5):379-385.
[11]王一多,金英玉,关秀茹.肾脏水通道蛋白-1(AQP-1)的研究进展[J].现代检验医学杂志,2016,31(3):162-164.WANG Yiduo,JIN Yingyu,GUAN Xiuru.Progress in the research of aquaporin-1(AQP-1)of the kidney[J].Journal of Modern Laboratory Medicine,2016,31(3):162-164.
[12]王尉,高志琪.慢性肾病贫血患者血清NGAL水平与缺铁状态的临床相关研究[J].现代检验医学杂志,2017,32(3):119-122.WANG Wei,GAO Zhiqi.Clinical study on NGALand iron status in patients with chronic renal anemia[J].Journal of Modern Laboratory Medicine,2017,32(3):119-122.
[2]文集,谢席胜,张明华,等.基于创新中医理论辨证施治慢性肾脏疾病的临床研究[J].四川大学学报(医学版),2014,45(1):34-38.WEN Ji,XIE Xisheng,ZHANG Minghua,et al.Management of chronic kindney disease guided by the theory of traditional Chinese Medicine:an experimental study[J].Journal of Sichuan University(Medical Edition),2014,45(1):34-38.
[3]张晓敏,刘宏,刘必成.高尿酸血症与慢性肾脏病发生发展关系的研究进展[J].东南大学学报(医学版),2013,32(1):114-117.ZHANG Xiaomin,LIU Hong,LIU Bicheng.Progress in the relationship between hyperuricemia and the development of chronic kidney disease[J].Journal of Southeast University(Medical Edition),2013,32(1):114-117.
[4]阙凤连,肖文霞,吴一行.2型糖尿病患者内生肌酐清除率与慢性并发症的关系[J].广东医学,2014,35(13):2022-2024.QUE Fenglian,XIAO Wenxia,WU Yixing.Relationship between creatinine clearance and chronic complications in patients with type 2diabetes[J].Guangdong Medicine,2014,35(13):2022-2024.
[5]PERALYA C A,SHLIPAK M G,JUDD S,et al.Detection of chronic kidney disease with creatinine,cystatin C and urine albumin-to-creatinine ratio and association with progression to end-stage renal disease and mortality[J].the Journal of the American Medical Association,2011,305(15):1545-1552.
[6]王小丽,刘瑞东.尿TGF-β1检测在诊断慢性肾炎中的临床应用[J].现代检验医学杂志,2015,30(1):88-90.WANG Xiaoli,LIU Ruidong.Clinical application of urinary tra-nsforming growth factor-beta(TGF-β1)measurement in diagnosing chronic nephritis[J].Journal of Modern Laboratory Medicine,2015,30(1):88-90.
[7]POSADA-AYALA M,ZUBIRI I,MARTIN-LOREN-ZO M,et al.Identification of a urine metabolomic signature in patients with advanced-stage chronic kidney disease[J].Kidney International,2014,85(1):103-111.
[8]PHISITKUL S,KHANNA A,SIMONI J,et al.A-melioration of metabolic acidosis in patients with low GFR reduced kidney endothelin production and kidney injury,and better preserved GFR[J].Kidney International,2010,77(7):617-623.
[9]GAO X,CHEN W,LI R,et al.Systematic variations associated with renal disease uncovered by parallel metabolomics of urine and serum[J].BMC Systems Biology,2012,6(1):S14.
[10]QI S,OUYANG X,WANG L,et al.A pilot metabolic profiling study in serum of patients with chronic kidney disease based on 1 H-NMR-Spectroscopy[J].Clinical and Translational Science,2012,5(5):379-385.
[11]王一多,金英玉,关秀茹.肾脏水通道蛋白-1(AQP-1)的研究进展[J].现代检验医学杂志,2016,31(3):162-164.WANG Yiduo,JIN Yingyu,GUAN Xiuru.Progress in the research of aquaporin-1(AQP-1)of the kidney[J].Journal of Modern Laboratory Medicine,2016,31(3):162-164.
[12]王尉,高志琪.慢性肾病贫血患者血清NGAL水平与缺铁状态的临床相关研究[J].现代检验医学杂志,2017,32(3):119-122.WANG Wei,GAO Zhiqi.Clinical study on NGALand iron status in patients with chronic renal anemia[J].Journal of Modern Laboratory Medicine,2017,32(3):119-122.