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

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.

Keywords: Acute kidney injury; Chronic kidney disease; Interleukin 18; Kidney injury molecule-1; Mesoamerican nephropathy; Neutrophil gelatinase-associated lipocalin.