Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Clinical Research Article
  • Published:

Hyperuricemia is associated with the progression of IgA nephropathy in children

Pediatric Research volume 94, pages 1057–1066 (2023)Cite this article

Abstract

Background

The objective of the study was to explore the potential biomarkers and risk factors in children with immunoglobulin A nephropathy (IgAN).

Methods

Untargeted metabolomics analysis was performed on children with IgAN before and after treatment. Subsequently, a retrospective study involving the past 15 years and a follow-up study were performed to verify the role of hyperuricemia in IgAN children.

Results

Serum metabolomics analyses showed that levels of serum xanthosine were closely related to the outcome of IgAN, and KEGG analyses showed that differential metabolites were significantly enriched in purine metabolism. Furthermore, retrospectively analyses of 252 children with IgAN showed that hyperuricemia was associated with poorer renal outcome. Logistic regression analysis showed that BMI, serum creatinine, eGFR, Lee’s grade III, and crescents were risk factors of hyperuricemia in children with IgAN. Kaplan–Meier analysis revealed that kidney progression-free survival in IgAN children with hyperuricemia was lower than that without hyperuricemia, especially in females.

Conclusions

We first performed a dynamic metabolomics study to reveal that hyperuricemia is closely related to the progression of IgAN in children. Then retrospective and follow-up studies confirmed that hyperuricemia is an important risk factor for poor renal outcomes. We need to pay more attention to the hyperuricemia in children with IgAN.

Impact

  • We first performed a dynamic metabolomics study to reveal that hyperuricemia was closely related to the progression of IgAN in children.

  • Retrospective analyses in past 15 years confirmed that IgAN children with hyperuricemia had poorer renal function and worse renal pathology.

  • The BMI, Scr, eGFR, Lee’s grade III, and crescents were risk factors of hyperuricemia in children with IgAN.

  • The long-term follow-up study showed that hyperuricemia was an important risk factor for poor renal outcome in children with IgAN.

  • We need to pay more attention to hyperuricemia in children with IgAN, especially in females.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Flowchart of serum samples screening for metabolomics study.
Fig. 2: Serum metabolomics analyses by UPLC-Q-TOF/MS.
Fig. 3: Clinical features of IgAN children and controls for metabolomics study.
Fig. 4: The correlation between baseline SUA and renal function in children with IgAN.
Fig. 5: Long-term outcomes in IgAN children with hyperuricemia or non-hyperuricemia.

Similar content being viewed by others

Data availability

The datasets used and analyzed in this study are available from the corresponding author upon reasonable request.

References

  1. Hassler, J. R. IgA nephropathy: a brief review. Semin. Diagn. Pathol. 37, 143–147 (2020).

    Article  PubMed  Google Scholar 

  2. Wyatt, R. J. & Hogg, R. J. Evidence-based assessment of treatment options for children with IgA nephropathies. Pediatr. Nephrol. 16, 156–167 (2001).

    Article  CAS  PubMed  Google Scholar 

  3. Wu, H. et al. Long-term renal survival and undetected risk factors of IgA nephropathy in Chinese children-a retrospective 1243 cases analysis from single centre experience. J. Nephrol. 33, 1263–1273 (2020).

    Article  PubMed  Google Scholar 

  4. Taherkhani, A., Farrokhi, Y. R., Mohseni, M., Saidijam, M. & Arefi, O. A. Chronic kidney disease: a review of proteomic and metabolomic approaches to membranous glomerulonephritis, focal segmental glomerulosclerosis, and IgA nephropathy biomarkers. Proteome Sci. 17, 7 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Rinschen, M. M., Ivanisevic, J., Giera, M. & Siuzdak, G. Identification of bioactive metabolites using activity metabolomics. Nat. Rev. Mol. Cell Biol. 20, 353–367 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Noone, D. G. & Marks, S. D. Hyperuricemia is associated with hypertension, obesity, and albuminuria in children with chronic kidney disease. J. Pediatr. 162, 128–132 (2013).

    Article  CAS  PubMed  Google Scholar 

  7. Mian, A. N. & Schwartz, G. J. Measurement and estimation of glomerular filtration rate in children. Adv. Chronic Kidney Dis. 24, 348–356 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Trimarchi, H. et al. Oxford Classification of IgA nephropathy 2016: an update from the IgA Nephropathy Classification Working Group. Kidney Int. 91, 1014–1021 (2017).

    Article  PubMed  Google Scholar 

  9. Xia, X. et al. Serum uric acid and mortality in chronic kidney disease: a systematic review and meta-analysis. Metabolism 65, 1326–1341 (2016).

    Article  CAS  PubMed  Google Scholar 

  10. Ponticelli, C., Podestà, M. A. & Moroni, G. Hyperuricemia as a trigger of immune response in hypertension and chronic kidney disease. Kidney Int. 98, 1149–1159 (2020).

    Article  CAS  PubMed  Google Scholar 

  11. Moriyama, T. et al. High uric acid level is a risk factor for progression of IgA nephropathy with chronic kidney disease stage G3a. J. Nephrol. 28, 451–456 (2015).

    Article  CAS  PubMed  Google Scholar 

  12. Shu, D. et al. Risk factors of progressive IgA nephropathy which progress to end stage renal disease within ten years: a case-control study. BMC Nephrol. 18, 11 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Molfino, T. et al. Hyperuricemia and obesity in North American and European Children with IgA nephropathy. Int. J. Nephrol. Kidney Fail. https://doi.org/10.16966/2380-5498.126 (2016).

  14. Chen, T. et al. Prediction and risk stratification of kidney outcomes in IgA nephropathy. Am. J. Kidney Dis. 74, 300–309 (2019).

    Article  PubMed  Google Scholar 

  15. Alexander, S. et al. Epidemiology, baseline characteristics and risk of progression in the first South-Asian prospective longitudinal observational IgA nephropathy cohort. Kidney Int. Rep. 6, 414–428 (2021).

    Article  PubMed  Google Scholar 

  16. Russo, E. et al. Long-term blood pressure behavior and progression to end-stage renal disease in patients with immunoglobulin A nephropathy: a single-center observational study in Italy. J. Hypertens. 38, 925–935 (2020).

    Article  CAS  PubMed  Google Scholar 

  17. Choi, W. J. et al. The serum uric acid level is related to the more severe renal histopathology of female IgA nephropathy patients. J. Clin. Med. 10, 1885 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Myers, G. L. et al. Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program. Clin. Chem. 52, 5–18 (2006).

    Article  CAS  PubMed  Google Scholar 

  19. Chertow, G. M., Burdick, E., Honour, M., Bonventre, J. V. & Bates, D. W. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J. Am. Soc. Nephrol. 16, 3365–3370 (2005).

    Article  PubMed  Google Scholar 

  20. Uwaezuoke, S. N., Ayuk, A. C., Muoneke, V. U. & Mbanefo, N. R. Chronic kidney disease in children: using novel biomarkers as predictors of disease. Saudi J. Kidney Dis. Transpl. 29, 775–784 (2018).

    Article  PubMed  Google Scholar 

  21. Zhu, B. et al. Uric acid as a predictor of immunoglobulin A nephropathy progression: a cohort study of 1965 cases. Am. J. Nephrol. 48, 127–136 (2018).

    Article  CAS  PubMed  Google Scholar 

  22. Liu, R. et al. Prevalence of hyperuricemia and gout in Mainland China from 2000 to 2014: a systematic review and meta-analysis. Biomed. Res. Int. 2015, 762820 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Jutabha, P. et al. Apical voltage-driven urate efflux transporter NPT4 in renal proximal tubule. Nucleosides Nucleotides Nucleic Acids 30, 1302–1311 (2011).

    Article  CAS  PubMed  Google Scholar 

  24. Xu, Y. et al. Association between dyslipidaemia and the risk of hyperuricaemia: a six-year longitudinal cohort study of elderly individuals in China. Ann. Med. 54, 2402–2410 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Sun, J. et al. Mediation effect of obesity on the association between triglyceride-glucose index and hyperuricemia in Chinese hypertension adults. J. Clin. Hypertens. 24, 47–57 (2022).

    Article  CAS  Google Scholar 

  26. Zha, D., Wu, S., Gao, P. & Wu, X. Telmisartan attenuates uric acid-induced epithelial-mesenchymal transition in renal tubular cells. Biomed. Res. Int. 2019, 3851718 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kovács, T. et al. Metabolic syndrome and other cardiovascular risk factors associated with the progression of IgA nephropathy. Clin. Kidney J. 6, 395–401 (2013).

    Article  PubMed  Google Scholar 

  28. Kataoka, H. et al. Overweight and obesity accelerate the progression of IgA nephropathy: prognostic utility of a combination of BMI and histopathological parameters. Clin. Exp. Nephrol. 16, 706–712 (2012).

    Article  CAS  PubMed  Google Scholar 

  29. Wu, C., Wang, A. Y., Li, G. & Wang, L. Association of high body mass index with development of interstitial fibrosis in patients with IgA nephropathy. BMC Nephrol. 19, 381 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lu, P. et al. Serum uric acid level is correlated with the clinical, pathological progression and prognosis of IgA nephropathy: an observational retrospective pilot-study. Peer J. 8, e10130 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Zhou, J. et al. Plasma uric acid level indicates tubular interstitial leisions at early stage of IgA nephropathy. BMC Nephrol. 15, 11 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Haas, M. et al. A multicenter study of the predictive value of crescents in IgA nephropathy. J. Am. Soc. Nephrol. 28, 691–701 (2017).

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Funding

This work was supported by the Sun Yat-sen University Basic Scientific Research Young Teacher Training Project (grant number: 19ykpy65); Guangdong Basic and Applied Basic Research Foundation (grant number: 2019A1515010694); Science and Technology Planning Project of Guangzhou, China (grant number: 202201011400); College Student Innovation and Entrepreneurship Program of Sun Yat-sen University (grant number: 202210651).

Author information

Author notes

  1. These authors contributed equally: Yuanyuan Xu, Xiaohong Zheng, Hongjie Zhuang.

Authors and Affiliations

  1. Department of Pediatric Nephrology and Rheumatology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

    Yuanyuan Xu, Xiaohong Zheng, Hongjie Zhuang, Ying Mo & Xiaoyun Jiang

  2. Division of Joint Surgery, Department of Orthopaedic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

    Hongyi Liao

  3. Laboratory of General Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

    Wen Li

Authors
  1. Yuanyuan Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaohong Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hongjie Zhuang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hongyi Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ying Mo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaoyun Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wen Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Y.X., Y.M., X.J., and W.L. contributed to the study design. Y.X., H.Z., and H.L. contributed to the serum sample and data collections. Y.X., X.Z., and H.Z. contributed to the data analysis and writing of the manuscript. Y.M., X.J., and W.L. contributed to the project supervision and review and editing of the manuscript, and all authors read and approved the final manuscript.

Corresponding authors

Correspondence to Ying Mo, Xiaoyun Jiang or Wen Li.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

This study was approved by the ethics committee of the First Affiliated Hospital of Sun Yat-sen University (No. [2016] 040 and [2020] 499). All the children and their guardians were informed and signed consent forms before the study.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, Y., Zheng, X., Zhuang, H. et al. Hyperuricemia is associated with the progression of IgA nephropathy in children. Pediatr Res 94, 1057–1066 (2023). https://doi.org/10.1038/s41390-023-02538-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41390-023-02538-w

Search

Advanced search

Quick links