Investigation Of Renal Disease By Urinary Metabolomic Analysis

Kidney disease is a common intractable disease that seriously jeopardizes human health.It has a long course of disease and is prone to recurrence,and often misses the best diagnosis and treatment time because the early symptoms are not obvious.The development of kidney disease to the end stage will lead to the loss of renal function with a series of metabolic disorders and the clinical manifestations are uremia,even life-threatening.Metabolomics techniques combining NMR(nuclear magnetic resonance)with statistical analysis provide a feasible methodological strategy for the study of the diagnosis and prognosis of kidney disease.In this study,a metabolomics method based on NMR was used to analyze the metabolic mechanism of obstructive nephropathy and uremia,providing scientific experimental data for the clinical diagnosis and prognosis of related renal diseases.The contents of this research mainly include two parts:The first part used NMR-based metabolomics technology to analyze metabolic changes during severe obstructive hydronephrosis and recovery of post-obstruction in rabbits.The metabolite changes can be used to identify the potential biomarkers for the severity of obstruction and the recovery after obstruction.The gradually decreased levels of 3-hydroxykynurenine,3-methylhistidine,creatinine,guanidoacetate,meta-¶-hydroxyphenylacetate and phenylacetylglycine and the gradually increased levels of acetate,alanine,citrate,glycine,lactate and methionine in urine could be regarded as the potential biomarkers for the occurrence and severity of ureteral obstruction.And the reduced levels of 3-methylhistidine,creatinine,guanidoacetate,hippurate,meta-hydroxyphenylacetate and methylguanidine and the elevated levels of 2-aminoisobutyrate,acetylcholine,citrate,lactate,lysine,valine and a-ketoglutarate in urine compared with the obstructed level could characterize the metabolic recovery of ureteral obstruction.At the same time,the results also demonstrated the practicability and availability of recovering renal functions of the patients with severe hydronephrosis in clinical practice by removing causes for obstruction.In the second part,clinical uremia was investigated by the combination of NMR spectroscopy,statistical analysis and urinary biochemical assays to provide the basis of the metabolic characteristics of uremia.The characteristic metabolites of uremia were identified from the urine of the uremia patients.The results showed that the urinary levels of 2-hydroxyisobutyrate,3-hydroxybutyrate,acetone,butyrate,glutamate,sarcosine,creatinine,lysine,N,N-dimethylglycine,citrate,asparagine,ethanol and ethanolamine were lower,while the urinary levels of branched-chain amino acids(including leucine,valine and isoleucine),taurine,lactate and glucose were higher in the patients with uremia than in the healthy subjects.The corresponding disturbed metabolic pathways were derived from the characteristic metabolites,in which amino acid,energy and lipid metabolisms were involved.The specific characteristic metabolites of uremia will be helpful to understand the underlying biochemical mechanism of the onset of uremia.