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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. [ABSTRACT FROM AUTHOR]

Background. An epidemic of chronic kidney disease (CKD) of non-traditional aetiology has been recently recognized by health authorities as a public health priority in Central America. Previous studies have identified strenuous manual work, agricultural activities and residence at low altitude as potential risk factors; however, the aetiology remains unknown. Because individuals are frequently diagnosed with CKD in early adulthood, we measured biomarkers of kidney injury among adolescents in different regions of Nicaragua to assess whether kidney damage might be initiated during childhood. Methods. Participants include 200 adolescents aged 12-18 years with no prior work history from four different schools in Nicaragua. The location of the school served as a proxy for environmental exposures and geographic locations were selected to represent a range of factors that have been associated with CKD in adults (e.g. altitude, primary industry and CKD mortality rates). Questionnaires, urine dipsticks and kidney injury biomarkers [interleukin-18, N-acetyl-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL) and albumin-creatinine ratio] were assessed. Biomarker con-centrations were compared by school using linear regression models. Results. Protein (3.5%) and glucose (1%) in urine measured by dipstick were rare and did not differ by school. Urine biomarkers of tubular kidney damage, particularly NGAL and NAG, showed higher concentrations in those schools and regions within Nicaragua that were defined a priori as having increased CKD risk. Painful urination was a frequent self-reported symptom. Conclusions. Although interpretation of these urine biomarkers is limited because of the lack of population reference values, results suggest the possibility of early kidney damage prior to occupational exposures in these adolescents. [ABSTRACT FROM AUTHOR]

Background: In Central America, an epidemic of chronic kidney disease of unknown cause disproportionately affects young male agricultural workers., Study Design: Longitudinal cohort study., Setting & Participants: 284 sugarcane workers in 7 jobs were recruited from one company in northwestern Nicaragua. Blood and urine samples were collected before and near the end of the 6-month harvest season., Predictors: Job category (cane cutter, seeder, seed cutter, agrichemical applicator, irrigator, driver, and factory worker); self-reported water and electrolyte solution intake., Outcomes & Measurements: Changes in levels of urinary kidney injury biomarkers normalized to urine creatinine level, including neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), N-acetyl-β-d-glucosaminidase (NAG), and albumin; serum creatinine-based estimated glomerular filtration rate (eGFR)., Results: Mean eGFR was 113 mL/min/1.73 m(2) and <5% of workers had albuminuria. Field workers had increases in NGAL and IL-18 levels that were 1.49 (95% CI, 1.06 to 2.09) and 1.61 (95% CI, 1.12 to 2.31) times as high, respectively, as in non-field workers. Cane cutters and irrigators had the greatest increases in NGAL levels during the harvest, whereas cane cutters and seeders had the greatest increases in IL-18 levels. Electrolyte solution consumption was associated with lower mean NGAL and NAG levels among cane cutters and lower mean IL-18 and NAG levels among seed cutters; however, there was no overall effect of hydration among all workers. On average, workers with the largest increases in NGAL and NAG levels during the harvest had declines in eGFRs of 4.6 (95% CI, 1.0 to 8.2) and 3.1 (95% CI, -0.6 to 6.7) mL/min/1.73 m(2), respectively., Limitations: Surrogate exposure measure, loss to follow-up., Conclusions: Results are consistent with the hypothesis that occupational heat stress and volume depletion may be associated with the development of kidney disease, and future studies should directly measure these occupational factors. The presence of urine tubular injury markers supports a tubulointerstitial disease that could occur with repeated tubular injury., (Copyright © 2016 National Kidney Foundation, Inc. All rights reserved.)

Background: There is an epidemic of chronic kidney disease (CKD) of unknown etiology in Central American workers., Objectives: To investigate changes and job-specific differences in kidney function over a 6-month sugarcane harvest season, explore the potential role of hydration, and measure proteinuria., Methods: We recruited 284 Nicaraguan sugarcane workers performing seven distinct tasks. We measured urine albumin and serum creatinine and estimated glomerular filtration rate (eGFR)., Results: eGFR varied by job and decreased during the harvest in seed cutters (-8·6 ml/min/1·73 m(2)), irrigators (-7·4 ml/min/1·73 m(2)), and cane cutters (-5·0 ml/min/1·73 m(2)), as compared to factory workers. The number of years employed at the company was negatively associated with eGFR. Fewer than 5% of workers had albumin-to-creatinine ratio (ACR) >30 mg/g., Conclusions: The decline in kidney function during the harvest and the differences by job category and employment duration provide evidence that one or more risk factors of CKD are occupational.