Among the modified risk factors for chronic kidney disease hyperhomocysteinemia (HHC) and hyperuricemia (HU) play an important role in the development of the cardiorenal continuum. The purpose of the research was to study the relationship between HHC and the functional state of the kidneys in children with impaired purine metabolism. Materials and methods used: a single-center one-stage (cross-sectional) study was conducted in 54 pediatric patients aged 9 to 15 y/o with purine metabolism disorders (in the form of isolated HU or in combination with hyperuricosuria) in Feb. 2017 - March 2021. The level of homocysteine in the blood serum was determined by enzyme immunoassay. Evaluated clearance, excreted fraction, filtered volume and reabsorption of uric acid; the glomerular filtration rate (GFR) was calculated. The two groups were distinguished: the [main] Group 1 of 26 children with HHC; and the [comparison] Group 2 of 28 children with normal homocysteine levels. Results: the frequency of diagnosis of HHC among the examined was 47.8%, which is almost 5 times higher than in the population. In the main group, the analysis of Spearman's rank correlation revealed a positive statistically significant correlation between the level of homocysteine and uric acid: Rs=0.32, p=0.048. In this group, the clearance of uric acid, its excreted fraction and filtered volume were statistically significantly lower, while reabsorption and GFR were higher relative to the comparison group. The daily excretion of uric acid directly correlated statistically significantly with its clearance (Rs=0.71, p<0.001) and excreted fraction (Rs=0.66, p=0.004) and inversely significantly correlated with the level of its reabsorption (Rs=- 0.66, p=0.004). Statistically significant direct correlation of blood homocysteine and creatinine levels (Rs=0.38, p=0.020) and inverse correlation with uric acid excretion (Rs=-0.38, p=0.020) were obtained. Conclusion: in children with impaired purine metabolism, HHC is associated with the early formation of tubular dysfunction, which is evidenced by a statistically significant decrease in the clearance of uric acid, its excreted fraction and filtered volume. The increase in GFR in this case probably reflects the formation of hyperfiltration as the initial stage of metabolic renal damage.
Thymic gland (thymus) represents a huge mystery for biology, medicine (primarily immunology), including pediatric issues. Complexity of the study is determined by the multiplicity of integral connections of thymus with other components of immune system, neuroendocrine, hematopoietic systems, connective tissue, different organs and cells which provide appropriate barrier function. Discerning the direct thymic function from this continuum, or determining specific role of molecular factors (neuropeptides, growth hormone, etc.) upon the immune physiology represents a problem which is not yet resolved. In this review article dedicated to the current state of the problem, we consider the morphological and functional relationships between thymus, neuroendocrine system and, in particular, with hormones of the somatotropic axis. These interactions may also manifest by clinical heterogeneity which may be associated with impaired morphogenesis (organogenesis) at a very early stage of embryogenesis; namely, under the influence of gene family that determine the fate of each segment of the embryo-Hox genes which control the expression of other, functionally interconnected genes. Previously, T lymphocytes produced by the thymus and brain neurons have been shown to express the same antigen (Thy antigen), which was considered a specific antigen of T lymphocytes. A common molecular language, mediated by the molecules of intercellular interaction, was revealed which is used for the signal exchange between the cells, tissues and organs regulating the three mentioned systems (nervous, endocrine and immune). The interest of pediatricians in this field is associated with definite concept of human ontogenesis, from birth to elderly age, with thymic gland playing the main role, since antenatal period to early childhood. The main line of reasoning in this research area is not only theoretical, but also important from practical point of view. Since any critical involution of the thymus is accompanied by reduced number of produced and exported cells, a hormone-based therapy may be an alternative strategy to restore the organ by increasing thymocyte proliferation, and exporting mature T cells to peripheral lymphoid organs. Great opportunities have been opened in clinical immunology due to development of effective epistemological methods, e.g., genetic knock-out, transgenic animal models with human stem cell transfer, transplantation of hematopoietic and immunopoietic cells in primary and secondary immunodeficiencies, immune cell malignancies, autoinflammatory diseases, and, finally, infections of the immune system.
The thymus is now considered a derivative of the immune system being, to greater extent, its central organ. Immunodeficiency states and immune dysregulation also depend on the quality of the thymus, which may be determined both genetically and by fetopathic approach as well as due to the possibility and mode of its intravital injuries, age-related involution over different periods of life. Not accidentally, there are various morphometric bipolar states of the thymus gland in the pediatric population (3-7%), whereas its size may be sufficiently larger or smaller than the reference variable values. In certain cases, the phenomenon of thymomegaly (for example, in newborns) is considered a result of genetic errors (neuro-endocrine-immune syndrome with thymomegaly) induced by the mutated Hox genes. This syndrome may also be associated with congenital heart disorders. Moreover, the excessive morbidity in respiratory infections (commonly, viral by their etiology) among young children with bipolar thymus conditions remains the subject of sharp discussions. Some works assessing immune status in the children subjected to forced thymectomy, e.g., during heart surgery, yielded quite controversial results, even in cases of subtotal removal of thymus gland.Dialectically, the concepts of “morphology” and “organ function” could not be separated from one another. The morphometric transformations in organs (even transient ones) occuring within the range of > 95 and < 5 percentiles, should be almost always underlied by a certain pathomorphosis which require verification of their causes and origin. Even today, however, the assessment of thymus pathomorphology in the deceased children is not always critical, being often descriptive. This situation is, probably, associated with extreme complexity of thymic morphology assessment. The final point seems to be not set in the discussion about immunodeficiency states or immune dysregulation among children with bipolar thymus transformations. This is due to current absence of reliable immune-mediated biomarkers, the limited availability of genetic diagnostics in primary immunodeficiency conditions, and a decreased interest of clinical science in the issues of bipolar conditions of the thymus gland at the early age, in the absence of longitudinal observations in this category of patients, etc. In this article, the authors attempt to draw attention of researchers to this problem.
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