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UDK 616-01/09-61
METABOLIC SYNDROME AND RISK OF CHRONIC KIDNEY DISEASE
Kh. I. Juraeva
Bukhara State Medical Institute, Bukhara, Uzbekistan
Keywords:
metabolic syndrome, chronic kidney disease, insulin resistance, obesity, dyslipidemia, arterial hyperten-
sion.
Таянч сўзлар:
метаболик синдром, буйракнинг сурункали касаллиги, инсулинга чидамлилик, семириш,
дислипидемия, артериал гипертензия.
Ключевые слова:
метаболический синдром, хроническая болезнь почек, инсулинорезистентность, ожирение,
дислипидемия, артериальная гипертензия.
Metabolic syndrome (MS) is a combination of disorders of carbohydrate metabolism, abdominal obesity,
dyslipidemia and arterial hypertension. Research shows that there is a strong link between MS and chronic kidney
disease (CKD). The factors for the development of CKD in metabolic syndrome are an increased level of insulin and
insulin resistance, reactive oxygen species, inflammatory mediators, biologically active substances, hormones, inflam-
matory cytokin, increased activity of coagulation factors, inhibition of the fibrinolytic system.
МЕТАБОЛИК СИНДРОМ ВА СУРУНКАЛИ БУЙРАК КАСАЛЛИГИ ХАВФИ
Х. И. Жураева
Бухоро давлат тиббиѐт институти, Бухоро, Ўзбекистон
Метаболик синдром (МС) - бу углевод алмашинуви бузилиши, қорин семириб кетиши, дислипидемия
ва артериал гипертензия билан кечувчи ҳолат бўлиб ҳисобланади. Тадқиқотлар шуни кўрсатадики, МС ва су-
рункали буйрак касаллиги (СБК) ўртасида кучли боғлиқлик мавжуд. Метаболик синдромда CБК ривожлани-
шининг омиллари инсулин ва инсулин қаршилигининг ошиши, реактив кислород турлари, биологик фаол
моддалар, гормонлар, яллиғланишли цитокинлар, плазма омилларининг фаоллиги, фибринолитик тизими фао-
лиятининг ошиши билан боғлиқ. МС билан оғриган беморларда буйраклардаги патологик бузилишлар микро-
васкуляр тубулалар атрофияси, интерстициал фиброз ва глобал ѐки сегментал склероз билан намоѐн бўлади.
Микроалбуминурия - бу МС нинг дастлабки белгиси.
МЕТАБОЛИЧЕСКИЙ СИНДРОМ И РИСК ХРОНИЧЕСКОЙ БОЛЕЗНИ ПОЧЕК
Х. И. Жураева
Бухарский государственный медицинский институт, Бухара, Узбекистан
Метаболический синдром (МС) это сочетание нарушения углеводного обмена, абдоминального ожире-
ния, дислипидемии и артериальной гипертензии. Исследования показывают, что существует тесная связь меж-
ду МС и хронической болезнью почек (ХБП). Факторами развития ХБП при метаболическом синдроме явля-
ются повышенный уровень инсулина и инсулинорезистентность, активные формы кислорода, биологически
активные вещества, гормоны, воспалительные цитокины, усиление активности факторов коагуляции, тормо-
жение фибринолитической системы. Патологические нарушения в почках у больных с МС проявляются мик-
рососудистой тубулярной атрофией, интерстициальным фиброзом и глобальным или сегментарным склеро-
зом. Микроальбуминурия является ранним маркером при МС.
Metabolic syndrome (MS), which is a combination of pathological phenomena in the form of
insulin resistance, abdominal obesity, dyslipidemia and obesity, is associated with an increased
risk of developing cardiovascular diseases, diabetes mellitus, non-alcoholic liver disease and has a
close relationship with chronic kidney disease (CKD).
Changes in kidney function are one of the most common manifestations of various diseases.
There is a clinical need for early intervention to prevent potentially detrimental changes in renal
function. Unfortunately, the diagnostic process is complicated by the asymptomatic nature of kid-
ney dysfunction for a certain time and the absence of early biomarkers of kidney damage.
Many studies link MS with CKD [10,11,12]. Each component of MS is associated with both
the onset and progression of CKD. For example, obesity is one of the significant risk factors for
deteriorating kidney function. An increase in BMI by 10% increases the likelihood of a decrease in
the glomerular filtration rate by 1.3 times [2]. The early stages of CKD are usually diagnosed acci-
dentally due to its asymptomatic course and lack of screening programs. A meta-analysis of eleven
studies involving 30146 patients showed that MS is associated with a decrease in the estimated
GFR (GFR) <60 ml / min / 1.73 m2 with an odds ratio (OR) of 1.55 [6].
Обзор литературы
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It should be noted that in a number of included studies there were no patients with diabetes
mellitus, which is not only a potential component of MS, but also a common cause of CKD. Thus,
in the NHANES III study, in which 7800 patients with initially normal renal function were ob-
served for 21 years, the OR for the development of CKD in patients with MS was 2.6 (95% CI:
1.68-4.03) [4]. It is not always easy to assess the pathogenetic relationship between MS and CKD,
despite their widespread occurrence.
As already mentioned, unlike CKD, for MS there are no uniform diagnostic criteria; individ-
ual components of MS have rather vague meanings and are sensitive to such unmeasurable factors
as lifestyle changes, drug effects, or acute diseases. The timing of both MS and CKD is often diffi-
cult to determine.
Oversimplification of the criteria for MS (for example, using only BMI without determining
the circumference of the waist and hips, ignoring ethnicity) further limits the final conclusions
about the links between MS and CKD.
Histological examination of the kidneys after nephrectomy in 146 patients [10] showed a
high prevalence of changes characteristic of CKD, including diffuse and segmental glomeruloscle-
rosis in patients with MS. Other features included a higher prevalence of tubular cell atrophy, in-
terstitial fibrosis, and arterial sclerosis. Another approach is to study intrarenal hemodynamics us-
ing ultrasound diagnostics, in which parenchymal renal damage in MS can be reflected by an in-
crease in the intrarenal resistance index.
MS as a cause of CKD.
More convincing than simply combining these conditions is the hy-
pothesis that MS acts as a cause of CKD. However, it is not yet clear whether there is one linear
mechanism that leads from MS to CKD, or there are a number of separate but interdependent
mechanisms leading to the development of MS and, at the same time, to kidney damage. In this
context, the most acceptable explanation is the action of a combination of risk factors leading to
increased expression of profibrotic factors and including insulin resistance, inflammation, im-
paired lipid metabolism and arterial hypertension [7].
At the same time, it is still impossible to exclude a simple association between the two com-
mon diseases. The most important pathogenetic factor of CKD among those listed is insulin re-
sistance. Insulin is itself an anti-inflammatory hormone. Insulin resistance that occurs in type 2
diabetes leads to inflammation, then oxidative stress is activated and the combined effect of these
factors contributes to kidney damage [3]. High insulin levels stimulate the release of insulin-like
growth factor 1 (IGF-1), which, in turn, increases the production of connective tissue growth fac-
tor, resulting in fibrosis [6].
Moreover, obesity can lead to an increase in the secretion of pro-inflammatory adipokines by
adipose tissue, such as leptin, interleukin-6, and TNF-
α [11].
Leptin enhances the intrarenal pro-
duction of profibrotic transforming growth factor beta (TGF-
β) [9].
In addition, TNF-
α
increases
the production of reactive oxygen species (ROS), which, in turn, contribute to renal endothelial
dysfunction, mesangial proliferation, and fibrosis [12]. At the same time, the secretion of anti-
inflammatory cytokines, such as, for example, adiponectin, can be reduced, which contributes to
the maintenance of insulin resistance. Adiponectin deficiency is associated with intimal thickening
and smooth muscle cell proliferation [3]. Hese vascular effects may be independent of insulin sen-
sitivity and may be present in CKD. Obesity also leads to an increase in glomerular volume, podo-
cyte hypertrophy, and proliferation of mesangial cells [6]. TG and FFA by themselves can be ne-
phrotoxic due to the expression of proinflammatory cytokines [7]. In association with arterial hy-
pertension, another component of MS, angiotensin II stimulates ROS synthesis, decreasing the for-
mation of NO synthase and causing damage to renal microvessels, ischemia, andtubulointerstitial
changes [3].
However, it is rather difficult to assess the contribution of each of the MS components to re-
nal dysfunction. In this regard, the presence of MS in itself is a fundamental risk factor for the de-
velopment of CKD, regardless of its individual components. There is one more hypothesis accord-
ing to which hyperuricemia, which is not a ―traditional‖ component of MS, promotes the develop-
Kh. I. Juraeva
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130
Table 1.
Potential mechanisms of CKD development in MS.
ment of CKD due to inhibition of nitric oxide production or in connection with the formation of
nephrolithiasis [3].
Studies generally support the notion of a direction of pathogenetic mechanisms from MS to
CKD, although further research is still needed on this issue. The potential mechanisms of CKD in
metabolic syndrome are summarized in Table 1.
Обзор литературы
Potential mechanisms of CKD development in MS
• Oxidative stress
• Increased pro-inflammatory cytokines (leptin, IL-6, TNF
α
)
• Increase in profibrotic factors (fibroblast growth factor, transforming growth factor
β
, type IV collagen)
• Increased glomerular volume and podocyte hypertrophy
• Damaging effect of triglycerides and free fatty acids
• Development of ischemia and microvascular damage (angiotensin II)
• Hyperuricemia
MS and CKD progression.
Several population studies have identified an association of MS
with the progression of CKD. After reaching CKD stage C3-4, the presence of MS increases the
risk of developing end-stage renal failure (ESRD) over the next 2-3 years, according to a study of
more than 15,000 patients [15]. In particular, impaired glucose metabolism, hypertriglyceridemia,
and arterial hypertension have been associated with an increased risk of ESRD.
Similarly, a gradual increase in insulin resistance was associated with a greater rate of de-
cline in glomerular filtration rate in a cohort of elderly CKD patients [12]. On the other hand, in
the later stages of CKD, MS as a risk factor for the progression of kidney disease becomes less sig-
nificant, possibly because CKD directly leads to a rapid progression in a vicious vicious circle.
Another study showed [5] that even if there is a correlation between MS and albuminuria, the ef-
fect of MS on the progression of CKD does not depend on the presence of albuminuria and its se-
verityn addition, proteinuria is a known risk factor for the progression of CKD to ESRD and is al-
so a omponent of some definitions of MS [3]. Despite a greater than 30% risk with MS, controlling
proteinuria mitigates the potential for significant reductions in GFR, ESRD, or death in the African
American Kidney Disease and Hypertension study [14]. If CKD develops, it is accelerated by risk
factors common to CKD and MS. First, obesity-related glomerular hyperfiltration supplements the
hyperfiltration induced by CKD itself, which leads to accelerated development of glomerulosclero-
sis [13].
Second, the activity of inflammatory processes and oxidative stress in CKD also increases
[58]. Arterial hypertension and hypertriglyceridemia are increasing. Insulin resistance can be in-
creased by both CKD and MS [8]. Third, insulin resistance can be associated with inflammation
and cause so-called "endoplasmic reticulum stress".
According to this theory [16], proteins with altered structural organization accumulate in the
lumen of the endoplasmic reticulum, suppressing insulin secretion by phosphorylation of the insu-
lin receptor (IRS-1). Finally, insulin resistance impairs renal hemodynamics by increasing reten-
tion sodium and affects the transfer of other cations and anions [3]. The activation of the sympa-
thetic nervous system is also detrimental to renal hemodynamics and promotes the development of
proteinuria. The latter promotes damage to podocytes in the nephron, and, ultimately, chronic tu-
bulointerstitial damage, thereby worsening the course of CKD [1].
Сonclusions.
Thus, there is a close relationship between MS and CKD. Patients with meta-
bolic syndrome are more likely to have a high risk of chronic kidney disease and the risk of micro-
albuminuria. With an increase in BMI, a persistent decrease in GFR occurs.
Renal damage in metabolic syndrome includes glomerular and tubular fibrosis, vascular re-
nal dysfunction. Risk factors for CKD in MS are: insulin resistance, obesity, dyslipidemia, high
blood pressure.
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Kh. I. Juraeva
