treatment with slimming pills containingAristolochia fangchi, an herb that is
frequently a component in several mixtures of plant preparations used in traditional
Chinese medicine. Ten years ago, the discussion started that the aristolochic acid
(AA) produced byAristlochia clemantisis the cause of endemic (Balkan) nephro-
pathy (EN). This disease results in kidney failure in some individuals who live in
endemic regions in Bosnia, Bulgaria, Croatia, Romania, and Serbia.^122 There is still
not a final proof that AA is the agent that causes it, but latest investigations
conclusively show big similarity between CHN and EN, and this agent is frequently
used for animal model studies of CHN and EN.^123 It was demonstrated that AA
forms adducts with the DNA that were documented in renal tissue samples of EN
patients with upper urinary tract malignancies.^124 The final conclusion is that the
dietary exposure to AA is a significant risk factor for EN and cancer of the upper
urinary tract in the final stage of this disease.^125 Genomic investigations show that
some individuals from the endemic region that have p53 gene alternation are
particularly prone to EN.^126 Proteomic investigation in animal model (mouse)
show increased concentration of cytoskeletal proteins, proteins involved in kidney
development, and inflammatory process in urin plasma and kidney tissue of inves-
tigated animals.^127 There is also a parallel discussion that DNA adducts of myco-
toxin ocratoxin A are also involved in long-term poisoning that causes EN.^128
Unfortunately, despite intensive genomic, proteomic, and newly also metabolomic
investigation of EN that also resulted in first positive results towards the use of these
technologies in personalized patient diagnosis and treatment, there is only limited
acceptance of responsible physicians and epidemiologists for use of these techno-
logies in EN care in affected regions of South Eastern Europe.^129
For other types of nephropathy and other kidney diseases, similar strategy for
omics investigation of body fluids (preferably urine) and tissue biopsies can be
used. The possibility for use of formalin-fixed biopsies opened new perspectives for
retrospective analyses of a large number of samples.^130 Genomic and proteomic
investigations were also performed for studying and early detection of IgA nephro-
pathy, a thin basement membrane nephropathy, and other types of glomerulo-
nephritis (see footnote 97). Genome-wide association study identifies susceptibility
of individuals with, e.g., deletion of CFHR1 and CFHR3 loci at chromosome 1q32,
(^122) Rucevic et al. ( 2012 ), pp. 79–90; Lincoln ( 2007 ), p. 148.
(^123) Yun et al. ( 2014 ), pp. 2055–2061; Rucevic et al. ( 2012 ), pp. 79–90.
(^124) Reljic et al. ( 2014 ), pp. 2348–2362; Grollman et al. ( 2007 ), pp. 12129–12134.
(^125) Gharavi et al. ( 2011 ), pp. 321–327.
(^126) Krasteva and Georgieva ( 2006 ), pp. 561–567.
(^127) Jelakovic et al. ( 2014 ), pp. 2020–2027.
(^128) Reljic et al. ( 2014 ), pp. 2348–2362.
(^129) Jelakovic et al. ( 2014 ), pp. 2020–2027.
(^130) Reljic et al. ( 2014 ), pp. 2348–2362.
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