Environmental exposures in young adults with declining kidney function in a population at risk of Mesoamerican nephropathy

Abstract

ObjectivesThere is an epidemic of Mesoamerican nephropathy (MeN) in Central America, where sugarcane production is prominent. Numerous causes are proposed, but to date limited evidence supports any one hypothesis. A nested case–control study using biosamples from a rural, community-based follow-up study of 350 young adults from Northwest Nicaragua at risk of MeN was conducted with the aim of characterising the associations between urinary concentrations of metals, pesticides and mycotoxins from samples collected in the first 6 months and decline in kidney function over 2 years.MethodsUrine samples collected at baseline (pre-sugarcane harvest) and the first 6 month follow-up (post-sugarcane harvest) visit were tested. Twelve metals and metalloids (aluminium, total arsenic, cadmium, chromium, cobalt, copper, lead, manganese, mercury, selenium, silicon and strontium) were analysed by inductively coupled plasma-mass spectrometry. Twelve pesticides or their metabolites (2,4-dichlorophenoxyacetic acid, 3-phenoxybenzoic acid, 4-fluoro-3-phenoxybenzoic acid, chloro-3,3,3-trifluoro-1-propen-1-yl-2,2-dimethylcyclopropanecarboxylic acid, cis/trans 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, ethylenethiourea, glyphosate, 4-chloro-2-methylphenoxy acetic acid, 3-hydroxy-pyrimetanil, 5-hydroxytiabendazole, hydroxy-tebuconazole and 3,5,6-trichloro-2-pyridinol) and two mycotoxins (ochratoxin A (OTA) and citrinin (CIT)) were analysed by liquid chromatography coupled-mass spectrometry. Differences in the creatinine-corrected urinary concentrations of the measured exposures between outcome groups (participants with stable vs declining kidney function) were examined.ResultsElevated levels of aluminium and total arsenic as well as metabolites of several pesticides were detected across the population. No differences were identified between the declining and stable groups in the levels of metals or pesticides tested. OTA and CIT were below the limit of detection.ConclusionsThe tested metals, metalloids, pesticides and mycotoxins were not associated with loss of kidney function in participants at-risk of MeN.

Chronic kidney disease of non-traditional origin in Mesoamerica: a disease primarily driven by occupational heat stress

“…A comprehensive review from 2017 (63) concluded that there was scarce evidence for an association, but recommended studies with adequate exposure assessment before definitely discarding pesticides as an important risk. More recently, the above-mentioned Nicaraguan community cohort did not observe an association of self-reported pesticide use and kidney dysfunction, including glyphosate, paraquat, cypermethrin and methomyl (58), and a case-control study nested in this cohort found no association between rapid decline of eGFR over two years and baseline urinary levels of 12 common pesticides or their metabolites, including 2,4-D, glyphosate, chlorpyrifos and pyrethroid insecticides (64). To date, the only suggestive finding in Mesoamerica in relation to pesticides is a 13% prevalence of CKD stage ≥3 in Las Brisas, El Salvador, similar for men and women, attributed to local groundwater contamination with toxaphene after the dismantling of a pesticide storehouse by the community (23), which suggests an isolated situation.…”

“…In Nicaragua, lead, cadmium, and uranium were not associated with biomarkers of kidney injury or kidney function among sugarcane workers and miners, whereas total arsenic was associated with kidney injury among workers with the highest urinary levels (28). However, a longitudinal study following urinary levels of 12 metals in the Nicaraguan general population found no association with cases of rapid kidney function decline (64). A systematic assessment of the probability that metals were potentially important, concluded that this was highly unlikely, firstly because no particularly high exposures have been found in populations at risk as compared to established dose-response relationships, secondly because the clinical and histopathological presentation of CKDnt is not in accordance with the usual renal metal toxicity findings (66).…”

A Pilot Study to Assess Inhalation Exposures among Sugarcane Workers in Guatemala: Implications for Chronic Kidney Disease of Unknown Origin

“…Further, biomonitoring studies that evaluate urinary metal concentrations in sugarcane workers before, during, and after a harvest operation remain critical to understanding and quantifying real-world exposures. The few Central America studies that have examined the relationship between exposure to nephrotoxic metals and acute or chronic renal effects have yielded varying results [ 14 , 67 , 68 , 69 ]. The fingerprint and concentration of heavy metals in the soil have likely changed due to the recent eruption of Fuego in 2018 and subsequent deposition of basaltic ash on the topsoil in the sugarcane fields.…”

A Systematic Review of Renal Pathology in Chronic Kidney Disease of Uncertain Etiology

“…73,74 However, recent studies and reviews report that the evidence is still inconclusive to support the presence of such environmental toxins, heat stress, or dehydration in affected patients. [75][76][77][78] Vervaet et al 38 also proposed a toxic etiological factor which acts via the calcineurin inhibition pathway based on the proximal tubular lysosomal lesions found in the Sri Lankan and Mesoamerican patients. This lesion was also found in one healthy control from Sri Lanka.…”