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Metabolitic profiling of amino acids in paraquat-induced acute kidney injury

  • Xiuxian Wan
  • XinHua Li
  • Qiang Wang
  • Bin Zheng
  • Chunyu Zhou
  • Xin Kang
  • Dayong Hu
  • Hui Bao
  • Ai PengEmail author
Original article

Abstract

Background

The herbicide paraquat (1, 1′-dimethyl-4, 4′-bipyridylium dichloride; PQ) is a poison well-known to cause delayed mortality due to acute kidney injuries (AKI). This study examines the changes in serum amino acids (AAs) metabolite profiles as surrogate markers of renal cell metabolism and function after paraquat poisoning.

Methods

To identify the metabolic profiling of free serum AAs and its metabolites, serum from 40 paraquat-poisoned patients with or without AKI is collected. LC-MS/GC-MS is performed to analyze AA molecules. A Cox proportional hazard model was used to assess for incidence of AKI. Receiver operating characteristic (ROC) curve is applied to evaluate AKI occurrence and prognosis.

Results

A total of 102 serum AAs and its metabolites were identified. Compared with non-AKI patients, 37 varied significantly in AKI patients. The univariate Cox proportional hazard model analysis revealed that the estimated PQ amount, plasma PQ concentration, urine PQ concentration, APACHE, SOFA scores and 16 amino acids correlated with the incidence of AKI. Further analyses revealed that 3-methylglutarylcarnitine, 1-methylimidazoleacetate, and urea showed higher cumulative hazard ratios for the occurrence of AKI during follow-up (P < 0.05). The area under the curve (AUC) of 3-methylglutarylcarnitine, 1-methylimidazoleacetate and urea were 0.917, 0.857, 0.872, respectively.

Conclusion

3-methylglutarylcarnitine, 1-methylimidazoleacetate and urea were associated with AKI in patients with paraquat intoxication.

Keywords

Paraquat Poisoning Acute kidney injury Amino acids Metabolic pathway 

Notes

Acknowledgements

This work received the support of grants from the National Natural Science Foundation of China Nos: 81270136, 81671897 (to A.P.), No: 81500508 (to H.B.), Shanghai Pujiang Program No: 15PJ1406800 (to H.B.), Shanghai international cooperation program No: 16410724200 (to H.B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declared that they have no conflict of interest.

Supplementary material

10157_2019_1702_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 13 KB)

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Copyright information

© Japanese Society of Nephrology 2019

Authors and Affiliations

  1. 1.Department of Nephrology and RheumatologyAffiliated Shanghai Tenth Clinical Medical College of Nanjing Medical UniversityNanjingChina
  2. 2.Department of NephrologyLianyungang Oriental HospitalLianyungangChina
  3. 3.Center for Nephrology and Clinical MetabolomicsTongji University School of MedicineShanghaiChina
  4. 4.Department of NephrologyQilu Hospital of Shandong University (Qingdao)QingdaoChina

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