Boris A' Katsnelson, Ekaterina P' Kireyeva, Sergey V' Kuzmin, Larissa I' Privalova,

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AN ASSOCIATION BETWEEN RENAL DAMAGE AND URINARY
CADMIUM AND LEAD LEVELS IN YOUNG RUSSIAN
CHILDREN EPIDEMIOLOGY AND INTERVENTION
Boris A. Katsnelson, Ekaterina P. Kireyeva,
Sergey V. Kuzmin, Larissa I. Privalova, Nina A.
Khrushcheva, Yaakov B. Beikin, Tatiana V.
Postnikova, Natalya S. Zhuravleva, Nina P.
Makarenko, Tamara D. Degtyareva, Anastasia V.
Porovitsina Ekaterinburg Medical Research
Center for Prophylaxis and Health Protection in
Industrial Workers The Urals Medical Academy
Center for Laboratory Diagnostics of Mothers
and Childrens Diseases - Ekaterinburg, Russia
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OBJECTIVES (a) to find out whether an incipient
renal damage in children dwellers of urban areas
in an industrial region could be associated with
the combined toxicity of cadmium and lead (b)
to test if such a damage can be beneficially
influenced by a combination of bio-protective
agents previously proven in an animal experiment
to be inhibitors of cadmium/lead nephrotoxicity.
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Stage I ANALYTICAL EPI-STUDY
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In 2004 and 2005 we examined 3 to 7 years old
preschool children from four towns in the Middle
Urals, three of them being polluted by the
copper industry. The location of those towns
within the boundaries of the Sverdlovsk Oblast
(together with its administrative center, city of
Ekaterinburg) as well as the location of this
Oblast within the Russian Federation are shown
on the maps.
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Moscow
Sverdlovsk Region
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Only those children were included into the
studied groups who had no known renal disease.
Urinary concentrations of Cd and Pb, and of
beta-2-microglobulin (B2u), along with standard
clinical laboratory indices, were measured in 89
children in the 2004 (Sredneuralsk Sysert)
cohort, and 184 in the 2005 (Pervouralsk Revda)
cohort. A case-control study design was used to
evaluate the association between B2u and body
burdens of Pb and Cd as measured by their
urinary levels. Cases were defined as those
with B2u levels above the median and controls
as those at or below the median. B2u levels
ranged from 10 to 1200 ug/L. In both studies
mean concentrations of both metals proved higher
in cases as compared with controls.
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Mean urinary concentrations of beta-2
microglobulin, Cadmium and Lead
) Sredneuralsk and Sysert median B2u level
100 µg/L. ) Pervouralsk and Revda median
B2u level 120 µg/L.
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Associations between Cd or Pb levels and the
probability of a child being classified as a case
(odds ratios adjusted for area, gender, town, and
individual risk factors proved statistically
significant in univariate regression analysis)
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Stage II ANIMAL EXPERIMENTAL STUDY
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In experiments on rats it was shown that Both
Cadmium and Lead, when administered repeatedly in
low doses as single toxics or in a dual
combination, cause renal damage manifested with a
lot of functional, biochemical and morphometrical
indices In doses equivalent as fractions of
respective acute LD50, sub-chronic nephrotoxicity
of Lead is higher as compared with that of
Cadmium A complex of bio-protectors comprising
pectin, glutamate, a multivitamin-multi-mineral
preparation, and a calcium supplement attenuates
the combined nephrotoxicity of these metals.
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Stage III AN INTERVENTIONAL EPI-STUDY
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In 2006 we examined 38 children aged 3-7
attending kindergartens in the town of
Krasnouralsk polluted with emissions from a big
copper smelter. This time children with renal
disturbances have not been excluded.
Concentrations of cadmium, lead, and beta-2
microglobulin (B2u) were measured in their
morning urine samples, along with liquid
crystallography and standard clinical laboratory
indices. All the tests were performed just
before and immediately after the 5 weeks period
during which the children were being given (with
the informed consent of their parents, and under
medical supervision) the bio-protective complex
previously tested in our animal experiment.
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The initial B2u levels in this group ranged from
20 to 3180 ug/L. Only 5 children (13.2) had
levels gt300 ug/L. However, many children were
found to have other renal abnormalities
Micro-urolithiasis seen with the polarization
microscopy (in 86.8 of children) which revealed
also the formation of birefringent lipoprotein
crystals characteristic of renal membranolysis of
different extent (in 100) and the presence of an
albuminous ring around the microscopy
preparation (in 65.7). One third of the group
had abnormally high urine relative density (gt
1025). After the bio-protective intervention
the prevalence of all these indices has
statistically significantly (plt0.05) diminished.
Metals and B2u levels has diminished as well.
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The mean concentrations (ug/L s.e.) of B2u, Cd
and Pb in the group of Krasnouralsk children
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CONCLUSIONS Urinary cadmium and lead
concentrations characteristic of children living
in polluted areas may be at least partially
associated with an incipient renal damage in
some of them. A beneficial renal effect
produced in children by a combination of
bio-protective agents previously proven in an
animal experiment to be inhibitors of
cadmium/lead nephrotoxicity may be considered as
additional circumstantial evidence of the said
association.