Pesticide exposure and end-stage renal disease risk among wives of pesticide applicators in the Agricultural Health Study

Abstract

Background Pesticide exposure has been found to cause renal damage and dysfunction in experimental studies, but epidemiological research on the renal effects of chronic low-level pesticide exposure is limited. We investigated the relationships between end-stage renal disease (ESRD) among wives of licensed pesticide applicators (N = 31,142) in the Agricultural Health Study (AHS) and (1) personal pesticide use, (2) exposure to the husband's pesticide use, and (3) other pesticide-associated farming and household activities. Methods AHS participants reported pesticide exposure via self-administered questionnaires at enrollment (1993–1997). ESRD cases were identified via linkage to the United States Renal Data System. Associations between ESRD and pesticide exposures were estimated with Cox proportional hazard regression models controlling for age at enrollment. Models of associations with farming and household factors were additionally adjusted for personal use of pesticides. Results We identified 98 ESRD cases diagnosed between enrollment and 31 December 2011. Although women who ever applied pesticides (56% of cohort) were less likely than those who did not apply to develop ESRD (Hazard Ratio (HR): 0.42; 95% CI: 0.28, 0.64), among women who did apply pesticides, the rate of ESRD was significantly elevated among those who reported the highest (vs. lowest) cumulative general pesticide use (HR: 4.22; 95% CI: 1.26, 14.20). Among wives who never applied pesticides, ESRD was associated with husbands' ever use of paraquat (HR = 1.99; 95% CI: 1.14, 3.47) and butylate (HR = 1.71; 95% CI: 1.00, 2.95), with a positive exposure–response pattern for husband’s cumulative use of these pesticides. Conclusions ESRD may be associated with direct and/or indirect exposure to pesticides among farm women. Future studies should evaluate indirect exposure risk among other rural populations.

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

“…In addition, significant correlation between eGFR and TPL ( r  = −0.26).Association of blood levels of OCs (from environmental exposures) with CKDu, mediated partially through genotype--------------Prevalent cases; specific and quantitative assessment for non-occupational exposures to OCs, study in a non-CKDu setting; some potential for inverse causation; low risk for confounding Explanation value: high Siddarth et al, 2014 [76]IndiaHospital-based case-control (prevalent cases)270 cases (140 M, 130 F): patients attending nephrology departments270 age and sex matched controls: staff or persons accompanying CKD patients in the hospitalConcentrations of organochlorine pesticides in bloodGST genotypingCKDu: eGFR <90 ml/min/1.73m 2 with or without proteinuria, for 3 monthsCases had significantly higher blood concentrations of α–HCH, γ-HCH, total HCH, α-endosulfan, β-endosulfan, aldrin, p,p’-DDE, and total pesticidesSignificant associations with CKDu for 3rd versus 1st tertile for α-HCH (OR = 2.52), γ-HCH (OR = 2.70), total-HCH (OR = 3.18), aldrin (OR = 3.07), α-endosulfan (OR = 2.99), and β-endosulfan (OR = 3.06). Total pesticides 3rd to 1st tertile OR = 2.73 [(1.46–9.47).CKDu patients having either one null or two null genotypes tend to accumulate majority of pesticides, whereas in healthy controls only in the subset with both null genotypes for some pesticides.Lebov et al, 2016 [97]USACohort (follow-up since 1993-1997)55,580 licensed pesticide applicators (320 ESRD)Self-administered questionnaires:Ordinal categories of intensity-weighted lifetime days for 39 specific pesticidesPesticide exposure resulting in medical visit or hospitalizationDiagnosed pesticide poisoningHigh level pesticide exposure eventESRDSignificantly increased HR for highest category of use vs non-users and significant exposure-response trends:Alachlor HR = 1.51 [1.08-2.13], p for trend 0.015Atrazine HR = 1.52 [1.11-2.09], p for trend 0.008Metolachlor HR = 1.53 [1.08-2.13], p for trend 0.008Paraquat HR = 2.15 [1.11-4.15], p for trend 0.016Pendimethalin HR = 2.13 [1.20-3.78], p for trend 0.006Permethrin HR = 2.00 [1.08-3.68], p for trend 0.031More than one medical visit due to pesticide use HR = 2.13 [1.17 - 3.89], p for trend for increasing number of doctor visits 0.04.Hospitalization due to pesticide use HR = 3.05 [1.67 to 5.58]Association between use of specific pesticides and ESRDAssociation between ESRD and exposures resulting in medical visits or hospitalization and ESRD--------------Large cohort with long follow-up; study in non-CKDu endemic regions; specific and quantitative exposure assessment; multiple comparisons; low risk for confounding Explanation value: high Lebov et al, 2015 [96]USACohort (follow-up since 1993-1997)31,142 wives of licensed pesticide applicators (98 ESRD)Self-administered questionnaires or telephone interview-direct exposures ( n  = 17,425): ordinal categories of intensity weighted lifetime use of any pesticide, 10 specific pesticides and 6 chemical classes-Indirect pesticide exposures (husband’s pesticide use) among wives without personal use ( n  = 13,717)-Indicators of residential pesticide exposureERSDHighest category of cumulative lifetime-days of pesticide use in general vs never personal use: HR 4.22 [1.26-14.2]Exposure-response trends for husband’s use o...…”

“…Most interesting is the association with paraquat, also implicated in ESRD among the wives of the applicators [96]. Paraquat is a widely used herbicide, including in the CKDu epidemic regions around the world, and its acute nephrotoxicy is well-known.…”

Chronic kidney disease mortality trends in selected Central America countries, 1997–2013: clues to an epidemic of chronic interstitial nephritis of agricultural communities

“…A plausible complementary explanation is that women living in farming communities are exposed to varying levels of environmental pollutants, even when not directly working in agriculture or working in other roles. A recent USA study of 32 000 wives of pesticide applicators, who had never applied pesticides themselves, showed their end-stage renal disease risk to be significantly correlated with their husbands’ cumulative pesticide exposure, suggesting that exposures to spray drift carried by their husbands may be involved 31. The mortality pattern observed in our study and concurrent research findings in this context suggest an exposure gradient or a dose–response effect that may explain disparities by sex in the case of the CINAC epidemic.…”

Urine Collection Methods for Non-Toilet-Trained Children in Biological Monitoring Studies: Validation of a Disposable Diaper for Characterization of Tebuconazole Exposure

“…The actual exposure and the potential adverse health effects of pesticides are largely unknown. Previous studies suggest that pesticide exposure could be associated with neurodevelopmental impairment, immunologic abnormalities, and end-stage renal disease (Gonzalez-Alzaga et al, 2015;Chen et al, 2015;VoPham et al, 2015;Thrasher et al, 1993;Cosselman et al, 2015;Lebov et al, 2015;Piccoli et al, 2016;Garcia et al, 2017). Especially in young children pesticides exposure could harm the development of the central nervous and endocrine system.…”