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 ------------- 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 ------------- 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 ------------- 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 ------------- 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 ------------- 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 ------------- 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 ------------- 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 ------------- 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 ------------- 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 ------------- 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 ------------- 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 ------------- Cross-sectional; exposure assessment specific for chemical groups, but unquantified Explanation value: medium |