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TYPE
Original Research
PAGE NO.
21-24
10.37547/tajmspr/Volume07Issue04-04
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SUBMITED
16 February 2025
ACCEPTED
17 March 2025
PUBLISHED
16 April 2025
VOLUME
Vol.07 Issue04 2025
CITATION
Azimova S.B., Urdasheva L.SH., & Khalikov H.D. (2025). Modern
pathogenetic aspects of urolithiasis development. The American Journal of
Medical Sciences and Pharmaceutical Research, 7(04), 21
–
24.
https://doi.org/10.37547/tajmspr/Volume07Issue04-04
COPYRIGHT
© 2025 Original content from this work may be used under the terms
of the creative commons attributes 4.0 License.
Modern pathogenetic
aspects of urolithiasis
development
Azimova S.B.
Tashkent Medical Academy, Uzbekistan
Urdasheva L.SH.
Tashkent Medical Academy, Uzbekistan
Khalikov H.D.
Tashkent Medical Academy, Uzbekistan
Abstract:
World experience accumulated in the study of
the problem from the standpoint of various fields of
knowledge indicates that urolithiasis is probably the
most polyetiological disease with a very complex
pathogenesis. Despite the successes achieved in the
treatment of urolithiasis, relapses of the disease within
5 years can occur in 50% of patients. Today, some
genetic polymorphisms associated with urolithiasis are
of particular interest: uromodulin, which is involved in
the regulation of vitamin D metabolism and calcium
metabolism. The study of the problem of urolithiasis has
reached a qualitatively new level in recent years due to
the use of a multidisciplinary approach and the
principles of evidence-based medicine. The expansion
of the study of the etiology and pathogenesis of the
disease, the development and application of high-tech
diagnostic and treatment methods have made it
possible to solve many problems.
Keywords:
Urolithiasis,
gene
polymorphism,
pathogenesis, etiological factor, diagnostics, morbidity.
Introduction:
Urolithiasis (urolithiasis) is one of the
most pressing health problems worldwide, as its
prevalence increases annually by 0.5
–
5.3%. The
significant prevalence of urolithiasis in the population
(at least 5% of the population of industrialized
countries) forces us to constantly study the etiology and
pathogenesis, look for effective mechanisms for
prevention and metaphylaxis, improve diagnostic
methods, and develop new technologies for
The American Journal of Medical Sciences and Pharmaceutical Research
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The American Journal of Medical Sciences and Pharmaceutical Research
conservative and surgical treatment [1]. The incidence
varies greatly in different countries of the world,
averaging: 1
–
5% in Asia, 5
–
9% in Europe, 13% in North
America, and up to 20% in Saudi Arabia [2].
The importance of urolithiasis has become especially
relevant in recent years due to global demographic
shifts. The constant shift in the age pyramid of society
in developed countries towards an increase in the
proportion of elderly and old age groups leads to an
increase in the incidence of urolithiasis, which is 8.8%
in men and 5.6% in women in the 65
–
69 age group,
compared to 3.7% and 2.8%, respectively, in the 30
–
34
age group [3]. The prevalence of urolithiasis in
countries such as the USA, Italy, Germany, Spain, and
Japan has doubled over the past 20 years, and has
increased especially rapidly in recent years [4]. Despite
the advances made in the treatment of urolithiasis,
relapses of the disease within 5 years may occur in 50%
of patients. World experience accumulated in the
study of the problem from the perspective of various
fields of knowledge indicates that urolithiasis is
probably the most polyetiological disease with a very
complex pathogenesis. There is still no unified concept
of the pathogenesis of urolithiasis. The development of
the disease is associated with a number of complex
physicochemical processes occurring both in the div
as a whole and in the kidney and urinary tract.
Currently, urolithiasis is considered a multi-etiological
disease resulting from dysfunction of the urinary
system, gastrointestinal tract, genetic, hormonal and
metabolic disorders [5]. Although the so-called "non-
modifiable" factors such as gender, ethnicity,
geographic location, and genetic characteristics play a
significant role in the etiology of urolithiasis [6],
however, the importance of "modifiable" risk factors
for urolithiasis, such as obesity, diabetes mellitus and
metabolic syndrome (MS), is attracting increasing
interest from researchers.
Currently, urolithiasis is recognized as a polyetiological
disease. The causes of its occurrence are traditionally
divided into exogenous and endogenous. Sometimes
they are closely interconnected, in some cases it is
possible to clearly identify one of the causes.
Exogenous causes include climate, biogeochemical
characteristics of soils, water, nutritional factors; social
and other causes [7]. Endogenous etiological factors
are inherent in the human div. They can be genetic,
congenital and acquired during a person's life [8]. In
the scientific literature, special attention is paid to the
role of exogenous factors in the etiology of urolithiasis.
These include climatic and geographical, dietary,
iatrogenic, socio-economic factors, professions and
others [9, 10]. Climate (air temperature, humidity,
precipitation, insolation) can contribute to an increase
or decrease in the incidence of nephrolithiasis.
Biogeochemical characteristics of the territory in which
the indigenous population permanently resides also
affect the incidence of urolithiasis to one degree or
another. The main causes here are the physicochemical
state of the soil, drinking water and local food products
depending on the level of micro-, macroelements and
vitamins [11, 12].
Endogenous etiological factors include changes in
kidney tissue [13], pathological changes in the kidneys,
urinary tract and urodynamics [14, 15], impaired
microcirculation in the kidneys and the presence of
infection in them [16], changes in the composition of
urine, increased excretion of lithogenic substances [1].
Among the leading endogenous etiological factors in the
development of nephrolithiasis, great importance is
attached to genetic factors, which can cause the
development
of
polygenically
inherited
membranopathy,
congenital
and
acquired
enzymopathies,
tubulopathies
and
metabolic
nephropathies, as well as some monogenic forms of
lithogenic substance metabolism disorders [17]. In the
last decade, the main direction of studying the genetic
risk factors for the development of urolithiasis has been
the identification of its association with polymorphic
variants of a particular gene. In foreign studies, an
association was found between the occurrence of
urolithiasis and the polymorphism of some genes, such
as KL [18], VDR [20], CASR [19], ORAI1 [21]. The N. A.
Lopatkin
Research
Institute
of
Urology
and
Interventional Radiology is also conducting studies on
the association of urolithiasis with polymorphisms of
various candidate genes. A relationship was found
between the occurrence of urolithiasis in the Russian
population and the polymorphism of the VDR and ORAI1
genes. No such dependence was found for the
TNFRSF11B, TNFSF11, ESR1, KL, CASR, SLC26A6 genes
[22]. An association was found between the
polymorphism of the ORAI1 gene and the development
of calcium oxalate urolithiasis [23]. A relationship was
established between the non-recurrent form of the
disease and the ORAI1 gene polymorphism, and
between the recurrent form and the CASR gene
polymorphism [24]. Comparison of the obtained data
with the results obtained by Y. Chou [21] in the only
foreign work on this gene, conducted in the Chinese
population, indicates that the relationship between
urolithiasis and the ORAI1 gene was identified in the
Russian and Chinese populations. In the only foreign
work [21] on the ORAI1 gene, conducted in the Chinese
population, an association of urolithiasis with the ORAI1
gene was also established. It is worth noting that the
Chinese work, with a similar volume of the main and
control groups, included only patients with calcium
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The American Journal of Medical Sciences and Pharmaceutical Research
urolithiasis and did not study the possible relationship
between the formation of multiple urinary stones and
the polymorphism of this gene.
An analysis of the literature showed that various
genetic risk factors for the formation of calcium,
including calcium oxalate, stones were identified in
studies by different authors for a number of
populations. And these hereditary factors in most
cases differ from those found in the present work. An
association of calcium oxalate urolithiasis with the
Klotho gene polymorphism (KL, rs3752472) was
established in the Chinese population [21], and a link
was also found with another polymorphism of the
specified gene (KL, rsG395A) and the development of
calcium urolithiasis in the Turkish population [25].
Polymorphisms of the CASR promoter 1 and CASR (rs
R990G) genes are considered a hereditary risk factor
for calcium oxalate urolithiasis in the Italian and Iranian
populations, respectively [26, 27]. As for the ORAI1
gene
(rs7135617),
its
association
with
the
development of calcium urolithiasis in the population
of Taiwan has been shown [26]. Thus, urolithiasis is a
multifactorial disease, the development of which is
based on the interaction of a number of genes and
factors such as high consumption of carbohydrates,
sodium, proteins, physical inactivity, etc. In the last ten
years, according to foreign literature, studies have
been conducted to study the association of one or
another gene polymorphism with urolithiasis. Today,
some genetic polymorphisms associated with
urolithiasis are of particular interest: those involved in
the regulation of vitamin D metabolism and
uromodulin in the regulation of calcium metabolism.
The study of the problem of urolithiasis has reached a
qualitatively new level in recent years due to the use of
a multidisciplinary approach and the principles of
evidence-based medicine. Expanding the study of the
etiology and pathogenesis of the disease, the
development and application of high-tech diagnostic
and treatment methods have made it possible to solve
many problems and raise new ones, to identify
prospects for future scientific and practical work.
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