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A multiple-metabolites model to predict preliminary renal injury induced by iodixanol based on UHPLC/Q-Orbitrap-MS and 1H-NMR

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Abstract

Background & aims

There are some problems, such as unclear pathological mechanism, delayed diagnosis, and inaccurate therapeutic target of Contrast-induced acute kidney injury (CI-AKI). It is significantly important to find biomarkers and therapeutic targets that can indicate renal injury in the early stage of CI-AKI. This study aims to establish a multiple-metabolites model to predict preliminary renal injury induced by iodixanol and explore its pathogenesis.

Methods

Both UHPLC/Q-Orbitrap-MS and 1H-NMR methods were applied for urine metabolomics studies on two independent cohorts who suffered from a preliminary renal injury caused by iodixanol, and the multivariate statistical analysis and random forest (RF) algorithm were used to process the related date.

Results

In the discovery cohort (n = 169), 6 metabolic markers (leucine, indole, 5-hydroxy-L-tryptophan, N-acetylvaline, hydroxyhexanoycarnine, and kynurenic acid) were obtained by the cross-validation between the RF and liquid chromatography-mass spectrometry (LC–MS). Secondly, the 6 differential metabolites were confirmed by comparison of standard substance and structural identification of 1H-NMR. Subsequently, the multiple-metabolites model composed of the 6 biomarkers was validated in a validation cohort (n = 165).

Conclusions

The concentrations of leucine, indole, N-acetylvaline, 5-hydroxy-L-tryptophan, hydroxyhexanoycarnitine and kynurenic acid in urine were proven to be positively correlated with the degree of renal injury induced by iodixanol. The multiple-metabolites model based on these 6 biomarkers has a good predictive ability to predict early renal injury caused by iodixanol, provides treatment direction for injury intervention and a reference for reducing the incidence of clinical CI-AKI further.

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Funding

The research was funded by the Major Program from the National Natural Sciences Foundation of China (82192914), Important Drug Development Fund, Ministry of Science and Technology of China (2019ZX09201005-002-007) and Tianjin Committee of Science and Technology, China (20ZYJDJC00120).

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Authors and Affiliations

  1. State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of China

    Liying Cheng, Liming Wang, Biying Chen, Chenxi Wang, Xiumei Gao & Lifeng Han

  2. First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210000, People’s Republic of China

    Mengxi Wang

  3. Tianjin Key Laboratory of Clinical Multi-Omics, Airport Economy Zone, Tianjin, 300308, People’s Republic of China

    Jie Li

  4. Department of Nephrology, Fuwai Huazhong Cardiovascular Hospital, Zhengzhou, 451464, People’s Republic of China

    Zhu Zhang

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  1. Liying Cheng
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  2. Liming Wang
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  3. Biying Chen
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  4. Chenxi Wang
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  5. Mengxi Wang
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  8. Zhu Zhang
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  9. Lifeng Han
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Contributions

LC collected and analyzed the experimental data. The manuscript was drafted by LC. LW and BC participated in research design. CW, MW and JL revised the paper. XG, ZZ, and LH guided the experiment and provided funding for the research. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Xiumei Gao, Zhu Zhang or Lifeng Han.

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Cheng, L., Wang, L., Chen, B. et al. A multiple-metabolites model to predict preliminary renal injury induced by iodixanol based on UHPLC/Q-Orbitrap-MS and 1H-NMR. Metabolomics 18, 85 (2022). https://doi.org/10.1007/s11306-022-01942-3

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