Evidence of nickel and other trace elements and their relationship to clinical findings in acute Mesoamerican Nephropathy: A case-control analysis

Rebecca S.B. Fischer, Jason M. Unrine, Chandan Vangala, Wayne T. Sanderson, Sreedhar Mandayam, Kristy O. Murray

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16 Scopus citations


Background Although there are several hypothesized etiologies of Mesoamerican Nephropathy (MeN), evidence has not yet pointed to the underlying cause. Exposure to various trace elements can cause the clinical features observed in MeN. Methods and findings We measured 15 trace elements, including heavy metals, in renal case-patients (n = 18) and healthy controls (n = 36) in a MeN high-risk region of Nicaragua. Toenails clippings from study participants were analyzed using inductively coupled plasma mass spectrometry. A case-control analysis was performed, and concentrations were also analyzed over participant characteristics and clinical parameters. Nickel (Ni) concentrations were significantly higher in toenails from cases (1.554 mg/kg [0.176–42.647]) than controls (0.208 mg/kg [0.055–51.235]; p<0.001). Ni concentrations correlated positively with serum creatinine levels (p = 0.001) and negatively with eGFR (p = 0.001). Greater Ni exposure was also associated with higher leukocyte (p = 0.001) and neutrophil (p = 0.003) counts, fewer lymphocytes (p = 0.003), and lower hemoglobin (p = 0.004) and hematocrit (p = 0.011). Conclusions Low-dose, chronic environmental exposure to Ni is a possible health risk in this setting. Ni intoxication and resulting systemic and renal effects could explain the clinical signs observed during early MeN. This study provides compelling evidence for a role of Ni in the acute renal impairment observed in this MeN high-risk population. Additional work to assess exposure levels in a larger and heterogeneous population, identify environmental sources of Ni and exposure pathways, and evaluate the link between Ni and MeN pathogenesis are urgently needed.

Original languageEnglish
Article numbere0240988
JournalPLoS ONE
Issue number11 November
StatePublished - Nov 2020

Bibliographical note

Funding Information:
study was partly funded by a grant from El Comité Nacional de Productores de Azúcar de Nicaragua (CNPA). The funder provided financial support to conduct study activities, but neither the funder nor owners or administrators of Nicaragua Sugar Estates Ltd nor Ingenio San Antonio, which serves as our study site, had influence or input on study design, conduct, analysis, decision to publish, or preparation of the manuscript. RF is supported by an NIH grant from Fogarty International Center (5K01TW010863). KM and WS receive compensation to serve on a Scientific Advisory Board for research into MeN in NSEL workers. This Board, nor its affiliation, played no direct role in this study.

Publisher Copyright:
© 2020 Fischer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ASJC Scopus subject areas

  • General


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