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Biomarkers of kidney injury among children in a high-risk region for chronic kidney disease of uncertain etiology

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Abstract

Background

Mesoamerican Nephropathy (MeN), a form of chronic kidney disease of uncertain etiology, is a leading cause of death in Central America. The disease often presents in young adult male agricultural workers and progresses rapidly. Given the young age at presentation, we hypothesized that children in Central America experience subclinical kidney injury prior to working life.

Methods

We assessed specimens from a cross-sectional study of youth, aged 7–17 years, predominantly residing in a high-risk region of Nicaragua (n = 210). We evaluated urinary concentrations and risk factors for kidney injury biomarkers neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), monocyte chemoattractant protein 1 (MCP-1), and chitinase-3-like protein 1 (YKL-40). We evaluated the association between biomarkers and contemporaneous eGFR and compared biomarker concentrations with reference values from healthy children in other countries.

Results

Median uNGAL, uIL-18, and uKIM-1 concentrations exceeded healthy reference values. A one-year increase in age was associated with 40% increase in odds of being in the highest quartile of uNGAL (OR 1.4; (95%CI 1.2, 1.5); p < 0.0001). Youth who reported ever experiencing dysuria had 2.5 times the odds of having uNGAL concentrations in the top quartile (OR 2.5; (95%CI 1.4, 4.6); p = 0.003). Girls had significantly higher concentrations of all biomarkers than boys. Nine percent of children demonstrated low eGFR (≤ 100 ml/min/1.73 m2), while 29% showed evidence of hyperfiltration (eGFR ≥ 160 ml/min/1.73 m2), both potentially indicative of renal dysfunction.

Conclusions

Children residing in regions of Nicaragua at high risk for MeN may experience subclinical kidney injury prior to occupational exposures.

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Data availability

Data analyzed in this study are included in this published article as supplementary information.

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Acknowledgments

The authors gratefully acknowledge study participants, their families, and the BU Nicaragua study team for their time and efforts. We thank Sinead Keogh and Iris Delgado at Boston University for research assistance. The authors also express gratitude to Dr. Michael McClean at Boston University for his guidance and expertise.

Funding

The parent study was funded by the Comité Nacional de Productores de Azúcar (CNPA) in Nicaragua. The nested study was funded by the Fundación Renal Iñigo Alvarez de Toledo (FRIAT) in Spain. The funders had no role in study design, collection, analysis, and interpretation of data, or in the preparation or writing of this manuscript.

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Authors and Affiliations

  1. Department of Environmental Health, Boston University School of Public Health, 715 Albany St., 430W, Boston, MA, 02118, USA

    Jessica H. Leibler & Madeleine K. Scammell

  2. Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain

    Oriana Ramirez-Rubio

  3. Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA

    Oriana Ramirez-Rubio, Juan José Amador Velázquez, Damaris López Pilarte, Salini Gadupudi & Daniel R. Brooks

  4. Division of Nephrology, Department of Medicine, Johns Hopkins Medicine, Baltimore, MD, USA

    Wassim Obeid & Chirag R. Parikh

  5. Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA, USA

    David J. Friedman

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  1. Jessica H. Leibler
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  2. Oriana Ramirez-Rubio
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Contributions

DRB, ORR, and JJAV conceived and designed the parent study. ORR, JJAV, and DLP carried out participant enrollment and managed data collection in Nicaragua. JHL, DRB, and ORR conceived the nested study. WO and CRP conducted and managed laboratory analyses of biomarkers and guided data interpretation. JHL led data analysis and specimen management and wrote the manuscript. MLS and DJF provided guidance and expertise on data analysis and interpretation. SG assisted in data analysis and manuscript preparation. All authors contributed to the final manuscript.

Corresponding author

Correspondence to Jessica H. Leibler.

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Conflict of interest

JHL, JJA, DLP, and DRB have received funding from Azucareros del Istmo Centroamericano (AICA) to support a study of agricultural workers in Nicaragua. AICA had no role in the current study.

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Leibler, J.H., Ramirez-Rubio, O., Velázquez, J.J.A. et al. Biomarkers of kidney injury among children in a high-risk region for chronic kidney disease of uncertain etiology. Pediatr Nephrol 36, 387–396 (2021). https://doi.org/10.1007/s00467-020-04595-3

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