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Table 1 Mesoamerican studies assessing the role of pesticides in CKD

From: Pesticide exposures and chronic kidney disease of unknown etiology: an epidemiologic review

Reference & country Study design Study population Pesticide exposure assessment Case definition/outcome(s) Main findings Pesticide association
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Validity and explanation valuea
Rugama et al., 2001 [85]
Nicaragua
Retrospective hospital-based case-control CKD hospitalizations during 2000: 165 cases, 334 non-CKD random hospital controls Pesticide use yes/no, extracted from clinical records CKD diagnosis at admission OR pesticide exposure = 5.5 [2.8 – 10.7] Positive association with pesticide exposure
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Prevalent cases; high risk of bias from exposure misclassification; high risk of confounding
Explanation value: low
Gracía-Trabanino et al., 2005 [86]
El Salvador
Cross-sectional survey Volunteer sample of 353 adult M, 292 coastal and 62 at 500 m above sea level (masl) Questionnaire:
Agricultural occupation yes/no
Pesticide exposure yes/no
Proteinuria >15 mg/L
CKD defined as SCr ≥1.5 mg/dL among proteinuria positive subjects
For proteinuria:
OR agricultural work = 1.62 [0.75-3.49]
OR pesticide exposure = 0.79 [0.42-3.47]
For SCr ≥1.5: no associations with agricultural work or pesticide exposures
No association with agricultural work
No association with pesticide exposure
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Cross-sectional; crude pesticide exposure assessment; possible confounding; possible selection bias in second phase
Explanation value: low
Torres-LaCourt et al., 2008 [88]
Nicaragua
Cross-sectional population-based survey Random sample of 337 adults aged 20-60 (129 M, 208 F) from 2 rural communities Questionnaire:
Current agricultural work yes/no
Mixing or applying pesticides yes/no
Previous pesticide intoxication yes/no
CKD stage 3 or higher (eGFR <60 ml/min/1.73m2) Results reported separately for the two communities, analyses not adjusted for potential confounders:
ORs current agricultural work = 1.87 [0.88-3.99] and 2.68 [1.12-6.39]
ORs mixing/applying pesticides = 2.11 [0.99-4.50] and 4.80 [2.33-9.89]
ORs previous pesticide intoxication = 1.22 [0.32-4.67] and 1.19 [0.31-4.59]
Positive association with agricultural work
Positive association with pesticide exposure
No association with previous pesticide intoxication
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Cross-sectional; crude exposure assessment; high risk for confounding
Explanation value: low
Sanoff et al., 2010 [89]
Nicaragua
Volunteer screening program with nested case-control analysis Screening: 997 volunteers aged >18 y (848 M, 149 F)
Case-control: 334 M, 112 cases
Questionnaire:
Field labor yes/no
Work with or exposure to pesticides yes/no
eGFR
Screening: <60 vs ≥ 60 ml/min/1.73m2
Case control: <60 vs ≥ 80 ml/min/1.73m2
Screening:
OR agricultural field labor = 2.48 [1.59-3.89]
OR pesticides = 1.38 [0.90-2.11]
Case -control:
OR agricultural field labor = 2.38 [1.44-3.93]
OR pesticides = 1.57 [0.97-2.55]
Positive association for agricultural field labor
Weak positive association with pesticide exposure
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Screening survey; crude exposure assessment; insufficient adjustment for potential confounders; likely selection bias
Explanation value: medium
O’Donnell et al., 2011 [90]
Nicaragua
Cross-sectional population-based survey; nested case-control analysis Random sample of 771 individuals aged ≥18 (298 M, 473 F) from 300 eligible households
Case-control: 98 cases, 221 controls
Questionnaire:
Agricultural work yes/no
Pesticide exposure yes/no
Mixing or applying pesticides yes/no
CKD ≥ stage 3 (eGFR <60 ml/min/1.73m2) Unadjusted/sex and age adjusted logistic regressions:
OR agricultural work = 2.09 [1.08-4.05]/1.00 [0.44-2.27])
OR any pesticide exposure = 2.45 [1.31 – 4.57]/1.85 [0.84, 4.07])
OR mixing or applying pesticides = 1.78 [1.09 – 2.91]/1.32 [0.66-2.64]
No association with agricultural work
Weak positive association with any pesticide exposure
No association with mixing or applying pesticides
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Cross-sectional; crude exposure assessment; likely confounding; likely selection bias
Explanation value: medium
Orantes et al., 2011 [91]
El Salvador
Community screening and cross-sectional survey 775 individuals age ≥ 18, (343 M, 432 F) Questionnaire:
Agricultural occupation yes/no
Contact with agrichemicals yes/no
CKD stages 1-5 (2 determinations with a 3-month interval) OR agricultural occupation = 1.35 [0.63–2.88]
OR contact with agrichemicals = 1.23 [0.66 – 2.31]
No association for agricultural occupation
No association for contact with agrichemicals
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Cross-sectional; crude exposure assessment; risk for confounding; incomplete strategy for statistical analyses
Explanation value: medium
Laux et al., 2012 [93]
Nicaragua
Community-based cross-sectional survey 267 adults (120 M, 147 F) Questionnaire:
Work with pesticides yes/no
Proteinuria OR work with pesticides = 1.09 [0.6–1.98] No association with pesticide exposure
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Cross-sectional; crude exposure assessment; study conducted in non-CKDu area
Explanation value: medium
Raines et al., 2014 [45]
Nicaragua
Cross-sectional population-based survey; nested case-control analysis 424 adults (166 M, 258 F)
280 in case-control analysis (78 cases)
Questionnaire:
Agricultural worker yes/no
Among subset of agricultural workers:
Lifetime days of:
-mixing pesticides
-applying pesticides
Self-reported history of accidentally inhaling pesticides
Degree of use of personal protective equipment (PPE)
eGFR <60 ml/min/1.73 m2
Case-control: <60 vs ≥ 90 ml/min/1.73 m2
OR agricultural worker 2.05 [0.61-6.90]
Subset agricultural workers:
Lifetime days of mixing and applying pesticides: p = 0.13 and p = 0.22 respectively
Level of PPE: p = 0.35
OR for accidental inhalation of pesticides = 3.14 [1.12 – 8.78]
Weak association with agricultural work
No association with main pesticide exposure indicators
No association with PPE
Accidental inhalation of pesticides associated with low eGFR, but pesticide inhalation without further specifications is not interpretable
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Cross-sectional; unclear exposure indicators, possible confounding
Explanation value: medium
Laws et al., 2015 & Laws et al., 2016 [73, 74]
Nicaragua
Cohort 284 sugarcane workers (251 M, 33 F), incl. 29 agrichemical applicators Job title: agrichemical applicator eGFR (ml/min/1.73m2)
Biomarkers of early kidney injury NGAL, NAG, IL-18, albuminuria
Mean change eGFR for pesticide applicators during harvest season −3.8 (−9.9, 2.3)
Mean changes of early injury markers for pesticide applicators during harvest season:
NGAL −0.1 μg/g (p = 0.9)
NAG -0.12 μg/g (p = 0.6)
IL-18 -1.2 ng/g (p = 0.6)
ACR +0.3 mg/g (p = 0.8)
No association between a job of spraying pesticides with decrease in kidney function or increase in indicators of early tubular damage over one cutting season
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Cohort design with short 6-month follow up; crude assessment with jobtitle for current exposure
Explanation value: medium
García-Trabanino et al., 2015 [94]
El Salvador
Cross-sectional occupational survey 189 sugarcane cutters (168 M, 21 F) Questionnaire:
Pesticide use yes/no
Use of specific pesticides yes/no:
Herbicides: glyphosate, paraquat, 2,4-D, triazines
Insecticides: specific organophosphates, carbamates, pyrethroids
eGFR <60 ml/min/1.73 m2 Ever use of any pesticide not associated with low eGFR
Ever use of carbamate insecticides: 74% among workers with reduced eGFR vs 29% among remaining workers and a significant predictor in multivariate model
Association with ever use of carbamate insecticides
No association with other groups of pesticides
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Cross-sectional; exposure assessment specific for chemical groups, but unquantified; multiple comparisons
Explanation value: medium
Wesseling et al., 2016 [99]
Nicaragua
Occupational cross-sectional study 86 sugarcane cutters, 56 construction workers, 52 subsistence farmers, all males Questionnaire:
Pesticide use ever yes/no
Use of specific pesticides yes/no: glyphosate, paraquat, 2,4-D, chlorpyrifos, cypermethrin
eGFR <80 ml/min/1.73 m2 Ever use of any pesticide and ever use of specific pesticides not associated with reduced eGFR, for all workers combined and in analyses restricted to cane cutters No association with ever use of pesticides
No association with any of the specific pesticides
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Cross-sectional; exposure assessment specific for chemical groups, but unquantified
Explanation value: medium
  1. Abbreviations: CKD chronic kidney disease (u: of unknown etiology; nt: not related to traditional risk factors), eGFR estimated glomerular filtration rate, ESRD end-stage renal disease, F female, M male, OR odds ratio [95% confidence interval], SCr serum creatinine, NGAL neutrophil gelatinase-associated lipocalin, NAG N-acetyl-D-glucosaminidase, IL-18 interleukin-18, ACR urinary albumin-to-creatinine ratio
  2. aExplanation value: The study’s ability to contribute to knowledge about potential associations between pesticides and CKD or CKDu (according to the objective of the study), based on a qualitative evaluation of design and the validity of the results. For details see Additional file 2: Table S1 and the main text