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Exploring potential predictors of Henoch-Schönlein purpura nephritis: a pilot investigation on urinary metabolites

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Abstract

Henoch-Schönlein purpura nephritis (HSPN) is the most severe manifestation of Henoch-Schönlein purpura (HSP). This study aimed to determine the role of urine metabolomics in predicting HSPN and explore the potential mechanisms of HSP. A liquid chromatography-tandem mass spectrometry-based untargeted metabolomics analysis was performed to investigate the urinary metabolic profiles of 90 participants, comprising 30 healthy children (group CON) and 60 patients with HSP, including 30 HSP patients without renal involvement (group H) and 30 HSPN patients (group HSPN). The differentially expressed metabolites (DEMs) were identified using orthogonal partial least squares discriminant analysis (OPLS-DA), and subsequent bioinformatics analysis was conducted to elucidate the perturbed metabolic pathways. A total of 43 DEMs between H and HSPN groups were analyzed by the Kyoto Encyclopedia of Gene and Genome (KEGG) database, and the result indicates that glycine, serine and threonine metabolism, and cysteine and methionine metabolism were significantly disturbed. A composite model incorporating propionylcarnitine and indophenol sulfate was developed to assess the risk of renal involvement in pediatric patients with HSP.

   Conclusion: This study reveals the metabolic alterations in healthy children, HSPN patients, and HSP patients without renal involvement. Furthermore, propionylcarnitine and indophenol sulfate may be potential predictive biomarkers of the occurrence of HSPN.

What is Known:

• HSP is the predominant type of vasculitis observed in children. The long-term prognosis of HSP is contingent upon the extent of renal impairment. In severe nephritis, a delay in appropriate treatment may lead to fibrosis progression and subsequent development of chronic kidney disease (CKD), even leading to renal failure.

• The application of metabolomics in investigating diverse renal disorders has been documented. Urine is a robust and sensitive medium for metabolomics detection.

What is New:

• The metabolic profiles were identified in urine samples of healthy children and those with HSP at the early stage of the disease. Different metabolites were identified between HSP patients without nephritis and those who developed HSPN.

• These different metabolites may affect oxidative stress in the progression of HSPN.

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Availability of data and materials

All the data are available from the corresponding author upon reasonable request.

Abbreviations

AUC:

Area under the curve

CI:

Confidence interval

CKD:

Chronic kidney disease

DEMs:

Differentially expressed metabolites

ESI:

Electrospray ionization

HMDB:

Human metabolome database

HSP:

Henoch-Schönlein purpura

HSPN:

Henoch-Schönlein purpura nephritis

IgAV:

IgA vasculitis

IgAVN:

IgA vasculitis nephritis

IS:

Indoxyl sulfate

KEGG:

Kyoto Encyclopedia of Gene and Genome

LC–MS/MS:

Liquid chromatography-tandem mass spectrometry

OPLS-DA:

Orthogonal partial least squares discriminant analysis

PCA:

Principal component analysis

ROC:

Receiver operating characteristic

ROS:

Reactive oxygen species

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Acknowledgements

The authors wish to extend their appreciation to the children and their families and the personnel at the health physical examination center of the Children’s Hospital of Soochow University for their assistance and support in participant recruitment.

Funding

The study was supported by the Medical Research Project of the Jiangsu Commission of Health (K2023049).

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Author notes

  1. Minyi Yu and Xiaoxiang Song contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology, Children’s Hospital of Soochow University, Suzhou, 215000, China

    Minyi Yu, Xiaoxiang Song, Jie Guo & Qihua Feng

  2. Department of Infectious Diseases, Children’s Hospital of Soochow University, Suzhou, 215000, China

    Jianmei Tian

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Contributions

MY, XS, and JT were responsible for study conceptualization. JG collected the urine samples and the clinical data. MY and XS generated data, analyzed results, and drafted the manuscript. QF and JT reviewed and edited the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jianmei Tian.

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Ethics approval and consent to participate

The study was approved by the ethics committee of the Children’s Hospital of Soochow University (2023CS180) and conducted under the Declaration of Helsinki. Informed consent was obtained from all patients’ parents.

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The authors declare no competing interests.

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Communicated by Peter de Winter

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Yu, M., Song, X., Guo, J. et al. Exploring potential predictors of Henoch-Schönlein purpura nephritis: a pilot investigation on urinary metabolites. Eur J Pediatr (2024). https://doi.org/10.1007/s00431-024-05573-9

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