4.2 Article

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

期刊

CLINICAL AND EXPERIMENTAL NEPHROLOGY
卷 23, 期 4, 页码 474-483

出版社

SPRINGER
DOI: 10.1007/s10157-019-01702-z

关键词

Paraquat; Poisoning; Acute kidney injury; Amino acids; Metabolic pathway

资金

  1. National Natural Science Foundation of China [81270136, 81671897, 81500508]
  2. Shanghai Pujiang Program [15PJ1406800]
  3. Shanghai international cooperation program [16410724200]

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BackgroundThe 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.MethodsTo 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.ResultsA 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.Conclusion3-methylglutarylcarnitine, 1-methylimidazoleacetate and urea were associated with AKI in patients with paraquat intoxication.

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