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.
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This study was partly funded by a grant from El Comité Nacional de Productores de Azúcar de Nicaragua (CNPA).
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.
Fischer, Rebecca S. B.; Unrine, Jason M.; Vangala, Chandan; Sanderson, Wayne T.; Mandayam, Sreedhar; and Murray, Kristy O., "Evidence of Nickel and Other Trace Elements and Their Relationship to Clinical Findings in Acute Mesoamerican Nephropathy: A Case-Control Analysis" (2020). Plant and Soil Sciences Faculty Publications. 149.
S1 Fig. Relationship between toenail Aluminum concentrations (log10-mg/kg dry nail mass) and select physiologic parameters. https://doi.org/10.1371/journal.pone.0240988.s001
pone.0240988.s002.docx (169 kB)
S2 Fig. Relationship between toenail Vanadium concentrations (log10-mg/kg dry nail mass) and select physiologic parameters. https://doi.org/10.1371/journal.pone.0240988.s002
pone.0240988.s003.docx (27 kB)
S1 Table. Toenail trace element concentrations (mg/kg dry nail mass) of renal patients and healthy controls, compared to healthy reference populations (n = 54). https://doi.org/10.1371/journal.pone.0240988.s003
pone.0240988.s004.docx (28 kB)
S2 Table. Heavy metals detected in toenails of renal patients and healthy controls (n = 54). https://doi.org/10.1371/journal.pone.0240988.s004
pone.0240988.s005.docx (33 kB)
S3 Table. Acute clinical presentation. https://doi.org/10.1371/journal.pone.0240988.s005
pone.0240988.s006.docx (40 kB)
S4 Table. Correlations between trace elements toenail concentrations (mg/kg dry nail mass) (n = 54). https://doi.org/10.1371/journal.pone.0240988.s006