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Artikova Magina Akmalovna, Tashkent Medical Pediatric Institute Assistant of the Hospital pediatrics department № 1
Uzbekistan, Tashkent E-mail: magina-1984@mail.ru
DYSMETABOLIC NEPHROPATY IN CHILDREN: ETIOPATHOGENESIS, THE ROLE OF OXALOBACTER FORMIGENES IN THE DEVELOPMENT OF SECONDARY OXALURIA
Abstract: The article presents modern views on the etiology and pathogenesis of metabolic nephropathies, kinds of crystalluria, data on the steady increase in the incidence of metabolic nephropathy, and also possible complications due to untimely diagnosis. Modern views on the role of intestinal microbiocenosis, especially oxalobacter formigenes in the development of metabolic nephropathy, are described.
Keywords: children, dysmetabolic nephropathy, secondary oxaluria, oxalobacter formigenes.
One of the current problems ofpediatrics at the present stage is not always precipitate; 2) the presence of calcium oxalate crystals,
diseases of the organs of the urinary system. The prevalence of the pathology of the urinary system in children varies from 60: 1000 to 187: 1000 in the children's population, depending on the environmental situation in the child's area of residence. At the same time, in the structure of the pathology of the organs of the urinary system, congenital and hereditary diseases predominate, with a latent course, among which a large proportion falls on metabolic dismeta-bolic nephropathies (DMN). The frequency of various dismetabolic nephropathies (DN) in children is unknown [1]. The factors that cause the risk of developing diseases ofkidney and discharge organs are not the same. At the moment, there is a marked decrease in immune parameters in children, which can affect the growth of the frequency of metabolic nephropathy [2]. A number of researchers in their scientific works show that the steady growth of metabolic disturbances is due not only to the combination of genetic, medical and biological risk factors, the presence of somatic pathology in children, but also to unfavorable environmental conditions [5; 6; 7; 8]. In connection with the active increase in the number of children suffering from dismetabolic disorders, there is an increase in the occurrence of tubulointerstitial damages to the kidneys, the formation of micro-lites and the formation of urolithiasis, while being the basis for the development of infections of the urinary system, which tend to be chronic and recurrent, which eventually leads to disruption of renal function [9]. At the same time, the infection of the urinary system in patients with metabolic disorders is the cause of stone formation [10]. Among DMNs associated with the violation of water-salt, phosphoric-calcium and other types of metabolism, special attention is paid to metabolic disturbances of oxalic acid, so-called DMN with oxalate-calcium crystalluria, reaching 20% of the total number of pathologies of the urinary system [1]. The variability of the prevalence of DMN with oxalate-calcium crystalluria according to different authors is due to differences in the environmental situation in the region where children live and can reach 31.4% [11]. The main signs that allow diagnosing dismetabolic nephropathy in children are crystalluria, which is characterized as follows: 1) the presence of "crystalloids" in elevated quantities — oxaluria, phosphaturia, calciuria, uraturia, ammonium-magnesium-phosphaturium, which
calcium phosphate, ammonium magnesium phosphate (tripolphos-phates), urate crystals; 3) the presence of promoters (amplifiers) of crystal formation (fibrinogen, etc.); 4) reduction of crystal formation inhibitors (inorganic pyrophosphate, citrate, glutamate and other organic acids); 5) pH value of urine: tripolphosphates precipitate in alkaline, and calcium phosphates, cystine, urates — in acidic environment [12]. However, the most common indicator that allows to detect dysmetabolic nephropathy in children is more or less constant oxalate-calcium crystalluria [13]. Such children have signs of endogenous intoxication and transient changes in the urinary syndrome: microproteinuria (microalbumin), fermenturia (phospho-lipase A and C, alkaline phosphatase, lactate dehydrogenase, beta-glucuronidase), and microhematuria. Large aggregated crystals of oxalates appear in the urine even with normal excretion of oxalates, which is associated with a decrease in the anticrystalline capacity of urine, the normal state of which depends mainly on the products of bioenergetic processes in mitochondria (inorganic pyrophosphates, citrates, etc.) [3; 13; 14; 15]. Oxalate-calcium crystalluria, as a rule, is detected in the form of single crystals, but mixed crystalluria can occur with the presence of crystals of calcium oxalate, calcium phosphate, and sometimes with urate crystals.
A number of foreign researchers believe that one of the main places in the development of metabolic nephropathies (oxaluria) belongs to the pathology of the digestive tract. Thus, dysbiotic intestinal disorders (in particular, lactobacillus deficiency) can lead to disturbance of oxalate degradation in the digestive tract, which is accompanied by increased absorption of oxalates in the intestine and the development of oxaluria (Mittal R. D., Kumar R. 2004). Interest is the study of the role of the anaerobic microorganism Oxalobacter formigenes. This microorganism produces an enzyme oxalyl-CoA-decarboxylase, which leads to the degradation of oxalates, which affects the regulation of the homeostasis of oxalate, preventing its absorption in the intestine. The results of the studies performed by Troxel S. A. et al. In 2003 in the USA, indicate a link between the presence of O. formigenes in the intestine and the development of hyperoxaluria. Due to the comparison of the O. formigenes genes sequence with other beta-proteobacteria, significant affinity to other
Section 3. Medical science
genera of bacteria such as, Telluria, Janthinobacterium and Dugan-ella, which are now related to the Oxalobacteracea family, has been revealed. For the human body is characterized by two groups Oxa-lobacter formigenes: I group is characterized by the content of cyclic 17 carbon fatty acids and group II cyclic 19 carbon acids [16]. The programming of the genomes of these 2 groups provided an opportunity to increase the concept of the biological importance of the microbe for the organism. As a result of the determination of the O.formigenes genomic sequence, scientists have opened the possibility for a more detailed study of the important biological properties ofbacteria for the organism [17]. It was determined that, in children up to 6-9 months, O.formigenes was not detected. In the first year of life, an increase in the population of O.formigenes is observed, by 6-8 years it is found in practically all children, and in adults in 60-80% of cases [21]. Decrease in colonization occurs in adulthood. In 20-40% of healthy adults this microorganism is not detected. It is not well known under what conditions a person is being colonized by a given bacterium. The prevalence of O. formigenes varies from 46% to 77% in the adult population. To the end, the sensitivity of O. formigenes strains to antibiotics and other medicinal products has not been studied [18]. Currently O.formigenes is the most effective oxalate absorbing microbiota of the intestine. Despite this, scientists do not exclude the role of other microorganisms in reducing the absorption of oxalates. Scientists V. R. Abratt, S. Reid (2010) suggest using bifido and lactobacillus as a probiotic in hyperoxaluria, taking into account the phylogenetic similarity of these microorganisms. Clinical studies examining the reduction of hyperoxaluria by the administration of O. formigenes or its enzymes show a promising trend, but the data need to be confirmed in larger, well-controlled
studies. Similar studies using Lactobacillus and Bifidobacterium also show a reduction in oxalate in vivo, but these data are still contradictory. In particular, further studies should determine whether there is a direct link between the absence of oxalic acid-absorbing bacteria and hyperoxaluria, and whether their absence is a risk factor for the development of secondary hyperoxaluria [19]. Studies have shown that prolonged use of antibiotics in children with cystic fibrosis can cause permanent decolonization of O.formigenes [20].
N. A. Korovina, I. N. Zakharova, L. P. Gavryushova, E. B. Mul-ladze (2007) noted that in children with metabolic nephropathies in the absence of correction of metabolic disturbances, the progression of membrane-destructive changes and formation of tubulointersti-tial nephritis and/or urolithiasis, as well as the development of the microbial inflammatory process in the renal tissue (pyelonephritis) with a decrease in renal function in the future — the formation of chronic renal failure, aggravating the course of the underlying disease. Progression of oxalate nephropathy often leads to the development of abacterial interstitial nephritis, and as a result of infection, pyelonephritis develops. The maximum expressed dizmetabolic disorders can cause the onset of urolithiasis, even in the first years of the child's life.
Thus, dysmetabolic nephropathy is a natural response to chronic effects on the kidneys of components of exogenous or endogenous intoxication — increased content of products of ordinary or disrupted metabolism, including peroxidation with reduced mitochondrial function, as well as various xenobiotics. The role of intestinal microbiota on the development of dysmetabolic nephropathy has not been fully understood, but the development of secondary oxaluria in children with chronic bowel diseases has been proved.
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