Metabonomics: on the Road to Detect Diagnostic Biomarkers in Endemic (Balkan) Nephropathy. Evaluation in a Retrospective Pilot Project
|Duquesne M1, Goossens C1, Dika Å½2, Conotte R1, Nortier J3, JelakoviÄ B2 and Colet JM1*|
|1University of Mons, Department of Human Biology & Toxicology, 20 Place du Parc, 7000 Mons, Belgium|
|2School of Medicine, University of Zagreb, Department for Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, Zagreb, Croatia|
|3Department of Nephrology, Erasme Hospital, Université Libre de Bruxelles, 808 Route de Lennik, B-1070 Brussels, Belgium|
|Corresponding Author :||Jean-Marie Colet
University of Mons
Department of Human Biology and Toxicology
20 Place du Parc
7000 Mons, Belgium
E-mail: [email protected]
|Received November 16, 2012; Accepted December 04, 2012; Published December 06, 2012|
|Citation: Duquesne M, Goossens C, Dika Å½, Conotte R, Nortier J, et al. (2012) Metabonomics: on the Road to Detect Diagnostic Biomarkers in Endemic (Balkan) Nephropathy. Evaluation in a Retrospective Pilot Project. J Cancer Sci Ther S18:002. doi:10.4172/1948-5956.S18-002|
|Copyright: © 2012 Duquesne M, 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.|
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Introduction: Endemic (Balkan) Nephropathy is a chronic renal disease mainly affecting rural populations in the valleys of the Danube. In the absence of renal replacement therapy, it leads to fatal kidney failure and is significantly associated with upper urothelial carcinoma. Bread poisoning with aristolochic acids is now widely accepted. The source of this toxic substance is considered to be Aristolochia clematitis, a perennial plant that invades farming fields. The poisoning with aristolochic acids was suggested when clinical and histopathological changes similar to those observed in the Balkan patients were reported in several cases of nephropathy in Belgian patients unintentionally exposed to aristolochic acids during a Chinese herbs diet. Those clinical and histopathological features were then reproduced in laboratory experimental models.
Methods: Using metabonomics, an emerging dynamic technique that allows an effective mapping of alterations in endogenous metabolites levels in biofluids and tissues, we evaluated early signs of renal toxicity from extra urine samples collected in a rat model of intoxication with aristolochic acids.
Results: Changes in urine composition were consistent with a proximal tubular damage, most likely initiated by a mitochondrial default and an inappropriate response to oxidative stress. The same metabonomic approach was applied to surplus of urine samples collected from Belgian and Croatian patients in clinical and epidemiological studies, respectively. It allowed a clear discrimination of the Belgian patients from a database of healthy volunteers. On the other hand, a trend to discrimination was noticed when comparing urine samples collected from individuals living in Croatian endemic regions as compared to Croatian non endemic villages. Finally, when included in the same analysis, both Belgian and Croatian patients displayed similar urine metabolic signatures, suggesting a common etiology of both diseases.