Efficiency of Enterosgel in kidney diseases in children living in the the cement
industry region.
Kudin M.V., Tsaregorodtsev A.D., Fedorov Y.N., Dlin V.V.
Federal State Budget Institution "Moscow Scientific and Research Institute of Pediatrics and
Pediatric Surgery", Russian Ministry of Health
Nowadays the problem of interaction between the environment chemical composition and the
health of the population is a challenge not only in Russia but also in other parts of the world [1,
2]. The level of overall health and quality of the environment (taking into account natural and
anthropogenic factors) are to different extent determined by biogeochemical features in different
regions of Russia. With intensification of industrial and human activities, urban growth, creation
of "megalopolises" and major industrial centers the load has increased so intensively that a
special ecological environment was formed, with high concentrations of anthropogenic products
– i.e. with a serious pollution of air, soil and water basins [3].
The contribution of anthropogenic environmental risk factors in the incidence of diseases in
children and adolescents, is 10-60% according to WHO. In the recent decades, study of diseases
caused by ecological factors related to toxic effects of the environment primarily of
anthropogenic origin is being developed. Among them, the increasing attention is drawn to
kidney diseases caused by exposure to heavy metals, especially in childhood. Thus, kidney
diseases caused by ecological factors in childhood often lead to the development of progressive
diseases in adults [4, 5].
One of pollution sources of the biosphere is chemical industry, including cement production.
According to regulations on quality control and environmental safety by international standards,
cement production is a source of mercury, strontium and zinc accumulation in the soil. The main
impact on the environment in cement production is associated with emissions of quickly
evaporating components in the form of dust, which in most enterprises exceeds the values
allowable for Russian national requirements [6, 7]. As a result of water and air transport of these
toxicants, areas located at a considerable distance may become contaminated.
Analysis of epidemiological data suggests that occupational diseases due to contact with the
cement during the production are among the most common [8, 9]. Data on the incidence in the
population of an area with cement industry are insufficient.
According to research of Dlin V.V. et al. (1994) [10], in the areas around a large cement plant
"Bryanskcement" the frequency of renal pathology in children was significantly higher than the
average Russian figure (29:1000) and was as high as 266 per 1,000 children examined. In the
structure of renal disease patients with predominated urinary tract infection (40%) and
dysmetabolic nephropathy (11%) dominated, while phosphate-calcium crystalluria was detected
more frequently than calcium-oxalate (50% and 15%, respectively), membranopatologic
disorders were detected as well.
According to Saratov special inspection of environmental control, pollution by chemical
elements including salts of heavy metals, in Volsk, Saratov region was: chrome – 1.5-8.6 times
greater than the maximum permissible concentration (MPC), zinc - 1.5-1.9 MPC, copper - 2-7
MPC, nickel 1,2-7 MPC, cadmium 2.3-16 MPC, lead 2.6 MPC, cobalt - 1.5-2.3 MPC [11].
High frequency of kidney diseases in children living in adverse environmental conditions result
in the the need to find treatment and prevention methods. In this respect, use of enterosorbent
Enterosgel seems interesting, which has shown the high clinical efficiency in the treatment of
dysmetabolic nephropathy [Gordeeva E.A., Alekseeva N.V., Kon’ I.J. et al, Use of enterosorbent
Enterosgel in children with dysmetabolic nephropathy / Pediatrics, No. 4 - 2005 - P.79-82].
Furthermore, enterosorbent has been successfully used to remove heavy metals and
radionuclides from the body. Thus, it has been proved that Enterosgel helps to normalize the
function of the excretory system by reducing the load on the natural detoxification system, in
particular by increasing the ability of serum proteins to bind toxins [Osadchaya O.I., Boyarskaya
A.M. Clinical efficacy of enterosorption for relief of endogenous intoxication in patients with
chronic ulcerative colitis/ Liki Ukraini, No. 6 (132). - 2009. - P. 87-89.]
Objectives: To determine the effectiveness of enterosorbent Enterosgel in kidney diseases of
children living in the areas of cement industry.
Characteristics of the surveyed groups of children and methods
A three-stage nephrology survey included 5851 children (M / W 2904/2947; 3,316 children aged
1 to 6 years and 2,535 children - from 7 to 18 years) living in the city of Volsk - a major center
of the cement industry (the main region). A similar program included 630 children (M / W
283/347; 158 children - 1-6 years, 472 children - 7-18 years) from the control region (village
Cherkasskoye), located at a distance of 50 km. a screening was conducted at Stage 1 (Table 1); at
Stage 2 - in-depth examination including urinalysis, urine culture for flora, daily proteinuria and
ultrasound examination of the urinary system; at Stage 3 children who had any changes at Stage
2 were examined in the local or regional nephrology departments with conduction, if necessary,
of urorentgenology surveys and urine quantitative studies.
Laboratory and instrumental studies included in the three-stage examination are presented in
Table 1.
Table 1. Lab tests used within the three-stage examination
No
.
Studied values
Number of
children
Study methods
Stage 1
1.
Studies of urobilinogen, glucose,
bilirubin, ketones (acetoacetic acid),
specific gravity, occult blood, рН,
protein, nitrites, leukocytes and
ascorbic acid in the urine
Main group –
5851
Express-analysis (in vitro) with
reactant strips CYBOW
(Korea, South) и DEKA PHAN
Control group
LEUCO (Czech Republic)
– 630
Stage 2
2.
Urine RBC and WBC,
miscroscopy for chtystalluria
urine
Main group –
4147. Control
group – 304
Nechiporenko test, first void
urine miscroscopy
3.
Size of kidneys, parenchyma, state of
pelvicalyceal system, vesicoureteral
reflux, bladder state.
Main group –
4147. Control
group – 304
Ultrasound study of kidneys
and urinoexcretory system
(apparatus MyLab-15,
Netherlands, with convex realtime linear transducer).
4.
Urine protein (24 h)
Main group –
4147. Control
group – 304
With nitric acid (Roberts
method)
5.
Definition of bacteriuria (for the main
indication)
Main group –
911. Control
group – 112
Method of urine culture on
Petri dish with nutrient agar
(Endo or Mc Conkey agar)
Stage 3
6.
Hb, erythrocytes, blood sedimentation
rate, leukocytes and blood fromula
Main group –
1706. Control
group – 110
CBC
7.
Serum protein, proteinogram,
холестерин, β-lipoproteins, urea,
creatinin, antistreptococcus
antibodies titres
Main group –
1706. Control
group – 110
Standard methods of
biochemical blood count
8.
Size of kidneys, parenchyma, state of
pelvicalyceal system, vesicoureteral
reflux, bladder state.
Main group –
1706. Control
group – 110
Ultrasound of kidneys and
urinoexcretory system, for the
main indication:
intravenous urography, voiding
cystography
9.
Creatinine concentration in the blood
serum, glomerular filtration rate
(Schwarz formula), water
reabsorption rate
10. Definition oft he distal tubule
function:
- study of concentration function;
Main group –
1706. Control
group – 110
Jaffe reaction on the
photoelectric calorimeter,
Main group –
1706. Control
group – 110
Zimnitsky test, blood and urine
osmolarity by electrothermal
method, on the osmometer
ОМКА 1ц – 01
Reberg test
- acidogenic function of kidneys
Urine рН (test strips),
evaluation of ammonia in the
study of uroproteinogram and
aminoaciduria
11.
- oxalate excretion
Sivorinovsky method (1969)
Of the children identified at Stage 3, 31 children with nephropathy (main group) from the core
region were selected for further treatment with Enterosgel (M / W 14/17; mean age 9.65 ± 1.13
years). Enterosgel was administered at a dose 1 dessert spoon 3 times a day, daily dose - 30 g for
1 month without concomitant therapy, including antibiotic therapy. The control group consisted
of 30 children with nephropathy from the same region, who did not receive Enterosgel (M / W
16/14; mean age 7.59 ± 1.29 years).
The main group included 17 (54.8%) of children with urinary system infection (USI), and 14
(45.2%) - with dysmetabolic nephropathy; the control group - 19 (63.3%) children with USI and
11 (36.7%) - with dysmetabolic nephropathy.
The groups did not differ significantly by gender, age and clinical diagnosis.
Clinical and laboratory examination and quantitative study of the chemical composition of
biological media (urine, nails, hair) was performed over time before treatment and 2 weeks after
the end of treatment in children of the main group and after 6 weeks of observation in children of
the control group.
The reference content of chemical elements in the urine was considered that of urinary excretion
in healthy children from potentially clean regions. Studies of chemical composition of biological
media over time in children of the main group, the control group and in healthy children from
potentially clean regions were conducted in the test analysis center (head of the center - MD,
Professor Yakshin V.V.), State Unitary Enterprise "Russian Research Institute of Chemical
Technology ", Russian Ministry of Atomic Energy by atomic absorption spectrophotometry with
inductively-coupled plasma ionization, on the apparatus «Varian Vista Pro CCD Simultaneous
ICP-OES »(USA)
Results
High rates of renal disease resulting from the three-stage nephrological examination was a
confirmation of the impact of ecopathogens on renal tissue of children living in the area of
cement production. Figure 1 shows the overall prevalence rates of renal diseases and certain
clinical forms in comparison with potentially safe (control) region.
174,6
Распространенность
нефропатий:
291,6
хронический
обструктивный…
тубулоинтерстициальн
ый нефрит
инфекция мочевой
системы
15.9
28,2
0
1,9
34.9
49.2
139.7
дисметаболическая
нефропатия
240.5
0
Группа сравнения
100
200
300
Основная группа
Figure 1. Incidence of renal diseases according their nosology in children of the main and control region
(per 1000 examined children)
Figure captions:
/Incidence of nephropathy – chronic obstructive kidney disease – tubular interstitial nephritis –
urinary system infection – dysmetabolic nephropathy/
Main group – Control group/
The effectiveness of treatment was assessed in terms of urinary syndrome dynamics, urine
oxalates and urinary excretion of chemical trace elements of danger classes 1 and 2 in children
before and 2 weeks after the end of the four-week course of treatment, i.e. 6 weeks after the first
examination.
Table 2 shows the dynamics of indicators of bladder syndrome and quantitative content of urine
oxalate in children treated with Enterosgel and in the control group at 6 weeks after the initial
examination.
Table 2.
Dynamics of urinary syndrome and quantitative indicators of oxalates
No.
Value
Main group (Enterosgel)
n=31
Control group
n=30
1.
2.
Protein, mg/l
WBC, µl
3.
RBC, µl
4.
Oxalates,
mg/24 h
2 weeks
after end of
treatment
33,0±5,8
15,7±2,8
34,95±
47,52±15,21
13,12
р
Initial
After6
weeks
р
<0,05
29,00±5,4
48,71±
21,02
14,00±
11,17
31,0±5,8
45,24±
10,69
10,09±
9,11
57,92±
2,75
>0,05
Initial
>0,05
14,33±11,12
4,21± 2,15
<0,05
64,09±3,56
39,18± 4,23
>0,05
64,68± 3,26
>0,05
>0,05
>0,05
In the group of children with renal disease treated with Enterosgel proteinuria decreased more
than twice, leukocyturia – by 1.43 times, erythrocyturia – by 3.4 times, oxaluria – by 1.6 times.
In the control group no significant differences were found in the content of oxalates and bladder
syndrome: a protein, leukocytes, erythrocytes,
Table 3
Dynamics of urinary syndrome and oxaluria on the background treatment, with the nosology
No.
1.
2.
Gorup
Protein
WBC
RBC
Oxalates
%
%
%
%
Decrease
93,5
45,2
77,4
48,4
No changes
6,5
41,9
16,1
32,3
Increase
Including urinary Decrease
system infection No changes
(n=17)
Increase
0
94,1
5,9
0
12,9
29,4
47,1
23,5
6,5
94,1
5,9
0
19,3
52,9
35,3
11,8
With
dysmetabolic
nephropathy
(n=14)
Decrease
No changes
Increase
92,9
7,1
0
64,3
35,7
0
57,1
28,6
14,3
42,8
28,6
28,6
Control group
n=30
Decrease
13,3
33,3
30,0
30,0
No changes
60,0
53,4
56,7
60,0
Increase
Including urinary Decrease
system infection No changes
(n=19)
Increase
With
Decrease
dysmetabolic
No changes
nephropathy
Increase
(n=11)
26,7
5,3
57,9
36,8
27,3
63,6
9,1
13,3
31,6
52,6
15,8
36,4
54,5
9,1
13,3
36,8
52,6
10,5
18,2
63,6
18,2
10,0
42,1
57,9
5,2
18,2
63,6
18,2
Main group
(Enterosgel)
n=31
Value
dynamics
In the study group, in most children proteinuria and microhematuria decreased, and in almost
half of the cases – leukocyturia and oxaluria. Increase of values was marked only in few cases.
Similar results were observed in the group of children with urinary infection and with
dysmetabolic nephropathy, except less frequent reduction of microhematuria in children with
dysmetabolic nephropathy (p <0.05) (Table. 3).
In contrast, positive dynamics in the comparison group was noted in less than a third of cases
and did not differ depending on nosology.
Thus, in the main group of children with renal disease in the region of cement production
improvement of urine values was demonstrated two weeks after the end of treatment with
Enterosgel in most cases, while without therapy with Enterosgel, either urinary symptoms or
oxaluria severity were maintained or the increase was observed.
Moreover, in all groups of children before and 2 weeks after the end of the 4-week course of
treatment, i.e. 6 weeks after initiation of therapy following trace elements were studied in the
urine over time, depending on the hazard class. Hazard class 1: cadmium (Cd), arsenic (As);
hazard class 2: antimony (Sb), chromium (Cr).
Table 4 shows the contents of chemical elements in the urine of children before and after
treatment with enterosorbent Enterosgel and in the comparison group. During treatment with
Enterosgel showed a significant increase in urinary excretion of toxic trace elements in children:
cadmium 2.2 times (p <0.05), antimony 2.7 times (p <0.05), arsenic - 1.75 times and Cr - 1.3
times in contrast to the comparison group, where the essential dynamics were observed.
Table 4 Dynamics of excretion of chemical elements (mg/l) in the urine of children treated with
Enterosgel
Control groups, n-30
Main group, n-31
N
o.
Chemical
elements
Initial
Two weeks
after the 4week
treatment
р
Initial
After 6
weeks
р
1
Cadmium
(Cd)
0,025±0,00
4
0,06±0,003
<0,0
5
0,001±0,000 0,001±0,000
>0,05
1
1
2
Arsenic
(As)
0,004±0,00
1
0,007±0,001
>0,0
5
0,005±0,000
0,007±0,002 >0,05
1
3
Antimony
(Sb)
0,015±0,00
1
0,04±0,001
<0,0
5
0,011±0,002 0,012±0,001 >0,05
4
Chrome
(Cr)
0,09±0,001
0,12±0,02
>0,0
5
0,12±0,05
0,13±0,05
>0,05
Conclusion
It has been established that the incidence of renal diseases in children in the regions of cement
industry is very high, especially regarding dysmetabolic nephropathy, unlike the control region,
which shows the significant role of environmental factors in the development of renal damage.
The conducted studies of Kudin M.V. (2012) [12] have shown that in children and adults living
in the area and having no renal diseases cadmium - toxic element, hazard class 1 - accumulates
in kidney tissue, which justifies the use of enterosorbent Enterosgel in persons living in the
region as a prophylactic purpose.
Enterosgel not only prevents accumulation of toxic substances into the body by their intestinal
adsorption, but also contributes to the removal of heavy metals from the urinary system.
Inclusion of Enterosgel in the therapy of children with renal diseases living in the region of
cement industry leads to the increased urinary excretion of cadmium, chromium, antimony, and
arsenic and improvement of urinary symptoms and, above all, reduction of proteinuria, reflecting
improved reabsorption function of the epithelium of proximal tubules.
No undesirable effects have been registered in children receiving Enterosgel.
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