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Investigating the potential causes of Mesoamerican Nephropathy (MeN)

Smpokou, Evangelia-Theano; (2021) Investigating the potential causes of Mesoamerican Nephropathy (MeN). Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Mesoamerican Nephropathy (MeN) has emerged as a major public health concern in Central America. MeN is not associated with traditional chronic kidney disease (CKD) risk factors, and the cause remains unknown. Our aim was to bring together evidence for and against potential causes of MeN. We used biosamples collected from 350 initially apparently healthy men and women aged 18-30 years from a population at risk of MeN to: (i) explore potential early biomarkers of kidney dysfunction, and (ii) quantify associations between possible nephrotoxins and change in renal function over a 2-year follow-up period. We quantified a range of serum and urinary markers of renal injury. Twelve metals and metalloids were analysed by inductively-coupled plasma-mass spectrometry. Twelve pesticides, their metabolites and two mycotoxins were analysed by liquid chromatography coupled to mass spectrometry. Differences in the creatinine-corrected urinary and serum concentrations of the measured exposures were examined between participants in different kidney function decline groups. Furthermore, the effect of heat and elevated fructose individually and in combination was assessed in vitro. The levels of urinary RBP, NGAL and serum UA were significantly elevated in the established kidney dysfunction group but did not help identify those with a normal baseline but declining function. Elevated levels of aluminium and total arsenic were observed across the population but no differences were identified between the different groups. Finally, in vitro experiments showed that heat stress suppressed the mRNA expression of MCP-1 but caused an early increase in expression of fibrogenic genes. Elevated fructose led to early mRNA increase in MCP-1, KIM-1, TGF-β, COLA1 and KIM-1 secretion. However, a number of these molecules were suppressed after longer term exposure. These findings provide evidence against the xenobiotic hypothesis investigated in this thesis as the primary cause(s) of MeN in Nicaragua. Future research priorities include examining alternative toxins not included in the present study and identification of more accurate biomarkers for the early detection of MeN.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Investigating the potential causes of Mesoamerican Nephropathy (MeN)
Event: UCL
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
URI: https://discovery.ucl.ac.uk/id/eprint/10124741
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