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Urinary cystatin C: pediatric reference intervals and comparative assessment as a biomarker of renal injury among children in the regions with high burden of CKDu in Sri Lanka

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Abstract

Background

Cystatin C (Cys-C) is an emerging biomarker of renal diseases and its clinical use, particularly for screening the communities affected by chronic kidney disease of unknown etiology (CKDu), is hindered due to the lack of reference intervals (RIs) for diverse ethnic and age groups. The present study aimed to define RIs for urinary Cys-C (uCys-C) for a healthy pediatric population in Sri Lanka and in turn compare the renal function of the residential children in CKDu endemic and non-endemic regions in Sri Lanka.

Methods

A cross-sectional study was conducted with 850 healthy children (10–17 years) from selected locations for reference interval establishment, while a total of 892 children were recruited for the comparative study. Urine samples were collected and analyzed for Cys-C, creatinine (Cr) and albumin. Cr-adjusted uCys-C levels were partitioned by age, and RIs were determined with quantile regression (2.5th, 50th and 97.5th quantiles) at 90% confidence interval.

Results

The range of median RIs for uCys-C in healthy children was 45.94–64.44 ng/mg Cr for boys and 53.58–69.97 ng/mg Cr for girls. The median (interquartile range) uCys-C levels of children in the CKDu endemic and non-endemic regions were 58.18 (21.8–141.9) and 58.31 (23.9–155.3) ng/mg Cr with no significant difference (P = 0.781). A significant variation of uCys-C was noted in the children across age.

Conclusions

Notably high uCys-C levels were observed in children with elevated proteinuria. Thus, uCys-C could be a potential biomarker in identifying communities at high risk of CKDu susceptibility.

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Data availability

The datasets generated during and/or analyzed during the current study are not publicly available due restrictions under the approval of the ethics review board, but are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank all the participants children who participated in the study, parents, academic and nonacademic staff members of the schools, government authorities school principals, teachers, and parents for their valuable support.

Funding

This research was funded by the Accelerating Higher Education Expansion and Development (AHEAD) Operation of the Ministry of Higher Education funded by the World Bank (No. AHEAD DOR 02/40).

Author information

Authors and Affiliations

  1. Department of Zoology, Faculty of Science, University of Ruhuna, Matara, 81000, Sri Lanka

    Patabandi Maddumage Mihiri Ayesha Sandamini, Pallage Mangala Chathura Surendra De Silva, Thibbotuwa Deniya Kankanamge Sameera Chathuranga Gunasekara, Sakuntha Dewaka Gunarathna & Ranawake Arachchige Isini Pinipa

  2. Department of Nephrology, Sri Jayewardenepura General Hospital, Colombo, 10100, Sri Lanka

    Chula Herath

  3. Department of Pharmacology, Faculty of Medicine, University of Ruhuna, Galle, 80000, Sri Lanka

    Sudheera Sammanthi Jayasinghe

  4. Department of Biosystems Technology, Faculty of Technology, University of Ruhuna, Matara, 81000, Sri Lanka

    Ediriweera Patabandi Saman Chandana

  5. The Nicholas School of the Environment, Duke University, Durham, NC, 27708, USA

    Nishad Jayasundara

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  1. Patabandi Maddumage Mihiri Ayesha Sandamini
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Contributions

SPMMA contributed to data curation, formal analysis, investigation, software, visualization, writing of the original draft, review and editing. DSPMCS contributed to conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, resources, software, supervision, validation, review and editing. GTDKSC contributed to data curation, formal analysis, investigation, software, visualization, writing of the original draft, review and editing. GSD contributed to data curation, formal analysis, and investigation. PRAI contributed to data curation and investigation. HC, JSS and CEPS contributed to resources, supervision, validation, review and editing. JN contributed to conceptualization, project administration, resources, supervision, validation, review and editing.

Corresponding author

Correspondence to Pallage Mangala Chathura Surendra De Silva.

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Ethical approval

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Review Committee of the Faculty of Medicine, University of Ruhuna (reference no: 2020.P.124; date: 29.01.2021). Informed consent to participate in the study have been obtained from the children and their parents.

Conflict of interest

No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article. None of the authors was involved in the journal’s review of, or decisions related to, this manuscript. The authors have no conflict of interest to declare.

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Sandamini, P.M.M.A., De Silva, P.M.C.S., Gunasekara, T.D.K.S.C. et al. Urinary cystatin C: pediatric reference intervals and comparative assessment as a biomarker of renal injury among children in the regions with high burden of CKDu in Sri Lanka. World J Pediatr 18, 196–205 (2022). https://doi.org/10.1007/s12519-022-00513-9

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  • DOI: https://doi.org/10.1007/s12519-022-00513-9

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