Diagnostic value of plasma tryptophan and symmetric dimethylarginine levels for acute kidney injury among tacrolimus-treated kidney transplant patients by targeted metabolomics analysis

Feng Zhang,Qinghua Wang,Tianyi Xia,Xia Tao,Shouhong Gao,Shen’An Chan,Wansheng Chen,Xiaojuan Xiong,Yan Wen,Shangxi Fu

doi:10.1038/s41598-018-32958-2

Abstract

Few literatures have evaluated the exact role of metabolomics in the identification process of potential biomarkers for acute kidney injury among the patients receiving renal transplantation. On top of this, the success of metabolomics in biomarker translation seems to lie in the robust quantitative method. As such, a single-center retrospective observational study was conducted enrolling 42 patients underwent renal transplantation with/without acute kidney injury, as well as 24 healthy volunteers, in Shanghai Changzheng Hospital. Plasma amino acid metabolic patterns for the participants were investigated by targeted UHPLC-MS/MS metabolic profiling. The most significant changes of the explored metabolites were related to the disturbance of tryptophan metabolism and arginine metabolism. Abnormal circulating tryptophan and symmetric dimethylarginine were identified to be potential biomarkers of acute kidney injury, combination of which showed a higher area under receiver-operator curve value (AUC = 0.901), improved sensitivity (0.889) and specificity (0.831) compared with creatinine only. Overall, these results revealed that targeted metabolomics analysis would be a potent and promising strategy for identification and pre-validation of biomarkers of acute kidney injury in renal transplantation patients.

Highlights

Acute kidney injury (AKI) is increasingly common and associated with transplant failure and death in renal transplantation patients
Arg was degraded to Cit by nitric oxide synthase (NOS), but Arg could be synthesized from Cit via the urea cycle enzymes argininosuccinate synthetase (ASS) and argininosuccinatelyase (ASL), which were mainly located in the proximal tubular cells[22]
Cit/Arg ratio showed no significant difference between NA and NB groups, Cit and Arg levels were higher in NB than those in NA group, which might be derived from the potential bidirectional conversion

Summary

Introduction

Acute kidney injury (AKI) is increasingly common and associated with transplant failure and death in renal transplantation patients. Our previous research revealed that concentrations of total AAs and many AAs, such as alanine, lysine, aspartic acid, serine, and methionine, were significantly altered in renal transplantation patients when compared to the healthy volunteers[14] This finding shed light on the meaning of the AA profile in renal transplantation patients, characterization of which would be necessary for understanding AKI process and identifying potential biomarkers for kidney dysfunction. The targeted metabolomics study was conducted in 42 patients underwent renal transplantation with/without acute kidney injury and 24 healthy volunteers, in a single-center retrospective observational study In this pre-validation study, the diagnostic accuracy of potential AA biomarkers was investigated using receiver operating characteristic (ROC) analysis

Methods

Results

Conclusion