THE EFFECT OF DIFFERENT TYPES OF HYPOXIA ON THE MORPHO-FUNCTIONAL STATE OF THE KIDNEYS OF FETUSES AND NEWBORNS: THE RESULTS OF OWN LONG-TERM EXPERIMENTAL STUDIES
PDF

Keywords

acute postnatal hypoxia
chronic intrauterine hypoxia
fetus
kidneys
mixed hypoxia
morphology
newborn

Abstract

Introduction. The vast majority of kidney diseases in children and adults have their origins in the antenatal, intranatal or postnatal periods of development. Poor health of women of childbearing potential, complications during pregnancy and delivery often lead to the development of various types of hypoxia (chronic intrauterine hypoxia (CIH), acute intranatal hypoxia, acute postnatal hypoxia (APH), mixed hypoxia (MH)). The latter are a common cause of fetal and neonatal disorders, leading to damage of various organs and systems, including the kidneys.

The purpose is to highlight the main results of own long-term experimental studies aimed at determining the effect of different types of hypoxia (CIH, APH, MH) on the morpho-functional state of the kidneys in fetuses and newborns.

Materials and methods. In this study, the author modelled alpine hypoxia using a sealed pressure chamber from which air was pumped out, creating conditions for a sharp decrease in atmospheric pressure. Every day, we placed mature female rats with an average weight of 220–250 g in conditions corresponding to 7,500 meters hight at 287 mm Hg for 20 minutes at the same time. During the experiment, we ranked the animals into four groups: group 1 – control group – pregnant female rats (n=3) that did not experience alpine hypoxia, some females were removed from the experiment in late gestation to remove fetuses (n=7). The offsprings (n=11) received from the rest of the females, were removed from the experiment on the first day after birth. Group 2 – a study group with simulation of CIH – pregnant female rats (n=4) throughout pregnancy (21 days) were subjected to daily alpine hypoxia, with some females removed from the experiment in late gestation to remove fetuses (n=6). Offsprings (n=10) from the rest of the females were removed from the experiment on the first days of life. Group 3 – a study group with modeling of APH – pregnant female rats (n=2) were not subjected to alpine hypoxia, but their offsprings (n=8) on the first day of life were subjected to alpine hypoxia once for 15 minutes, and then they were removed from the experiment. Group 4 – a study group for modeling MH – pregnant female rats (n=3) throughout pregnancy were subjected to daily alpine hypoxia, then the offsprings obtained from them (n=8) on the first day of life were subjected to alpine hypoxia once for 15 minutes and removed from the experiment. Histological, histochemical, immunohistochemical, morphometric and statistical research method were used.

          Results. Acute postnatal, chronic intrauterine and mixed hypoxia lead to the development of respectively minimal, moderate and pronounced morphological changes in the capsules, parenchymal and stromal-vascular components of the kidneys, primarily damaging the vessels of the stroma and parenchyma, where more pronounced changes occur in the tubules, collecting tubules, and in chronic intrauterine hypoxia these changes increase in newborns compared to fetuses. Experimental hypoxia causes the development of hemodynamic disorders, degenerative-desquamative changes of vascular endotheliocytes, epitheliocytes of Bowman's capsules, tubules, collecting tubules, and the latter in acute postnatal hypoxia are observed mainly in the proximal tubules, and in chronic intrauterine and mixed hypoxia in all parts of the tubular system and collecting tubules. Chronic intrauterine and mixed hypoxia promote cyst formation, delay the processes of glomerulogenesis and tubulogenesis. Acute postnatal, chronic intrauterine and mixed hypoxia stimulate fibroblastic cells in the kidneys, and chronic intrauterine and mixed hypoxia also induce epithelial-mesenchymal transformation, causing the development of sclerosis. Acute postnatal, chronic intrauterine and mixed hypoxia induce apoptosis, proliferation, leading to an imbalance between them due to the prevaling proliferation in acute postnatal and chronic intrauterine hypoxia and apoptosis in mixed hypoxia.

          Conclusions. Identified morphological changes in the kidneys of fetuses and newborns developed under the influence of acute postnatal, chronic intrauterine and mixed hypoxia, given the unity of structure and function, will lead to functional changes in these organs in subsequent postnatal ontogenesis in such children and the emergence of different nephrological pathology. This study actualizes the implementation of preventive measures among persons of reproductive age, dictates the need for quality pre-pregnancy training, which should be aimed at timely detection and treatment of genital and extragenital pathology in women.

Key words: acute postnatal hypoxia, chronic intrauterine hypoxia, fetus, kidneys, mixed hypoxia, morphology, newborn.

https://doi.org/10.35339/ic.9.1.86-92
PDF

References

Halle, M. P., Lapsap, C. T., Barla, E., Fouda, H., Djantio, H., Moudze, B. K., … & Priso, E. B. (2017). Epi-demiology and outcomes of children with renal failure in the pediatric ward of a tertiary hospital in Cameroon. BMC Pediatrics, 17(1), 202. doi: 10.1186/s12887-017-0955-0.

Plumb, L., Boother, E. J., Caskey, F. J., Sinha, M. D., & Ben-Shlomo, Y. (2020). The incidence of and risk factors for late presentation of childhood chronic kidney disease: a systematic review and meta-analysis. PLoS One, 15(12), e0244709, doi: 10.1371/journal.pone.0244709

Kamath, N., Iyengar, A., George, N., & Luyckx, V. A. (2019). Risk factors and rate of progression of CKD in children. Kidney International Reports, 4(10), 1472‒1477. doi:10.1016/j.ekir.2019.06.004

Fomina, S. P. (2021). Hronichna hvoroba nyrok u ditej v Ukrai'ni [Chronic kidney disease in children in Ukraine]. Ukrainian Journal of Nephrology and Dialysis, 1(69), 16‒26.

Newsome, A. D., Davis, G. K., Ojeda, N. B., & Alexander, B. T. (2017). Complications during pregnancy and fetal development: implications for the occurrence of chronic kidney disease. Expert Review of Cardiovascular Thera-py, 15(3), 211‒220. doi:10.1080/14779072.2017.1294066

Brophy, P. (2017). Maternal determinants of renal mass and function in the fetus and neonate. Seminars in Fetal and Neonatal Medicine, 22(2), 67-70. doi: 10.1016/j.siny.2017.01.004.

Zhylka, N. Y., Slabkiy, G. O., & Shcherbinska, O. S. (2021). Stan reproduktyvnogo zdorov’ja zhinok v Ukrai'ni [The state of female reproductive health in Ukraine]. Reproductive endocrinology, 4(60), 67‒71.

Oxburgh, L., Muthukrishnan, S.D., & Brown, A. (2017). Growth factor regulation in the nephrogenic zone of the developing kidney. Results and Problems in Cell Differentiation, 60, 137‒164. doi: 10.1007/978-3-319-51436-9_6.

Morozov, S. L., Mironova, V. K., & Dlin, V. V. (2021). Postgipoksicheskoe porazhenie pochek u detej rannego vozrasta [Post-hypoxic lesion of kidneys in babies]. Practical medicine, 19(2), 28‒33.

Coats, L. E., Davis, G. K., Newsome, A. D., Ojeda, N. B., & Alexander, B. T. (2019). Low birth weight, blood pressure and renal susceptibility. Current Hypertension Reports, 21(8), 62. doi: 10.1007/s11906-019-0969-0.

Dorzhu, U. V., Shoshenko, K. A., Belichenko, V. M., & Ayzman, R. I. (2014). Ontogeneticheskie izmenenija strukturnyh pokazatelej pochek krys [The ontogenic changes of the kidney structure parameters at the rats]. Fundamen-tal research, 12(6), 1201‒1206.

Abdullina, G. A., Safina, A. I., & Daminova, M. A. (2014). Klinicheskaja fiziologija pochek u nedonoshen-nyh: rol' dinamicheskogo nabljudenija [Clinical physiology of the kidneys in premature: the role of follow-up]. The Bulletin of Contemporary Clinical Medicine, 7(6), 9‒13.

Al Salmi, I., & Hannawi, S. (2020). Birth weight and susceptibility to chronic kidney disease. Saudi Journal of Kidney Diseases and Transplantation, 31(4), 717‒726. doi: 10.4103/1319-2442.292305.

Stritzke, A., Thomas, S., Amin, H., Fusch, C., & Lodha, A. (2017). Renal consequences of preterm birth. Mo-lecular and Cellular Pediatrics, 4(1), 2. doi: 10.1186/s40348-016-0068-0.

Pogodaeva, T. V., & Luchaninova, V. N. (2012). Prognozirovanie formirovanija zabolevanij pochek u ploda i novorozhdennogo [Prediction of the development of fetal and neonatal renal diseases]. R Bulletin of Perinatology and Pediatrics, 4(1), 75‒80.

Sorokina, I. V., Markovsky, V. D., Borzenkova, I. V., Myroshnychenko, M. S., & Pliten, O. N. (2016). Mor-fologicheskie osobennosti klubochkovogo apparata pochek plodov i novorozhdennyh pri modelirovanii razlichnoj gi-poksii [Morphological features of the glomerular apparatus of fetuses and newborns kidneys in modeling different hy-poxia]. Morphologia, 10(3), 267‒272.

Kim, S. H., Park, S. J., Han, K. H., Kronbichler, A., Saleem, M. A., Oh, J., … & Shin, J. I. (2016). Patho-genesis of minimal change nephrotic syndrome: an immunological concept. Korean journal of pediatrics, 59(5), 205‒211. doi: 10.3345/kjp.2016.59.5.205.

Smirnov, A. V., Spasov, A. A., Panshin, N. G., Solovyova, O. A., & Kuznetsova, V. A. (2015). Morfolo-gicheskie preobrazovanija pochek krys pri jeksperimental'nom modelirovanii diabeticheskoj nefropatii. [Structural trans-formations of rat kidneys in experimental diabetic nephropathy]. V Journal of Medical Research, 3, 25‒27.

Panakhova, N. F., Gasanov, S. Sh., Akhundova, A. A., Aleskerova, S. M., & Polukhova, A. A. (2014). Funkcional'naja harakteristika pochek nedonoshennyh novorozhdennyh, rodivshihsja u materej s prejeklampsiej [Func-tional characterization of the kidneys of preterm infants born to mothers with preeclampsia]. R Bulletin of Perinatology and Pediatrics, 3, 57‒62.

Ow, C. P. C., Ngo, J. P., Ullah, M. M., Hilliard, L. M., & Evans, R. G. (2018). Renal hypoxia in kidney disease: cause or consequence? Acta Physiologica (Oxf), 222(4), e12999. doi: 10.1111/apha.12999.

Sene, L. B., Scarano, W. R., Zapparoli, A., Gontijo, J. A. R., & Boer, P. A. (2021). Impact of gestational low-protein intake on embryonic kidney microRNA expression and in nephron progenitor cells of the male fetus. PLoS One, 16(2), e0246289. doi: 10.1371/journal.pone.0246289.

Myroshnychenko, M., Sherstiuk, S., Zubova, Y., & Nakonechna, S. (2017). Patogenno inducirovannyj apop-toz, obuslovlennyj gipoksicheskim vozdejstviem, v organah mochevoj sistemy plodov i novorozhdennyh (jeksperi-mental'noe issledovanie) [Pathogenically induced apoptosis caused by hypoxic effects in the urinary system organs of fetuses and newborns (experimental study)]. Georgian medical news, 9(270), 94‒99.

Sorokina, I. V., Myroshnychenko, M. S., & Korneyko, I. V. (2017). The features of smooth muscle actin ex-pression in the kidneys, ureters and bladder of the newborns exposed to chronic intrauterine, acute postnatal and mixed hypoxia. The new Armenian medical journal, 11(2), 33‒39.

Kim, D. H., Xing, T., Yang, Z., Dudek, R., Lu, Q., & Chen, Y. H. (2017). Epithelial mesenchymal transition in embryonic development, tissue repair and cancer: a comprehensive overview. Journal of Clinical Medicine, 7(1), 1. doi: 10.3390/jcm7010001.

Pasechnik, D. (2014). Rol' jepitelial'no-mezenhimal'nogo perehoda v geneze hronicheskoj bolezni pochek i pochechno-kletochnogo raka (problemy i perspektivy) [The role of epithelial-mesenchymal transition in the pathogene-sis of chronic kidney disease and renal cell carcinoma (problems and prospects)]. International Humanitarian Universi-ty Herald, 6, 30‒33.

Dongre, A., & Weinberg, R.A. (2019). New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Natural Reviews Molecular Cell Biology, 20(2), 69‒84. doi: 10.1038/s41580-018-0080-4.

Sorokina, I., Myroshnychenko, M., & Kapustnyk, N. (2017). Pathology of the urinary system organs in chil-dren population of Ukraine: its past, present and future. Regional Innovations, 4, 35‒42.

Copyright for articles published in the journal is regulated by the License Agreement for the use of a scientific article in the journal, which is concluded between the author of the article (Licensor) and Kharkov National Medical University (Licensee, publisher of the journal "Inter Collegas"). The licensor grants to the Licensee a non-exclusive non-exclusive license for the use of the article (a license that does not exclude the use of the article by the Licensor and the issuance of licenses to others for use of this article) on the terms and for the period specified in the contract. The licensor (the author of the article) grants the Licensee the right to reproduce the article (publication in the journal "Inter Collegas", publication, duplication, duplication or other reproduction of the article without limiting the circulation of copies, each copy of the article must contain the name of the Licensor; Of general information, including the publication of the article in full or in part on the Internet on the journal page, the right to use the metadata of the article (titles, full names of authors, annotations, bibliography eskih materials) through the dissemination and communication to the public, processing and systematization, as well as inclusion in various databases and in-formational system).

The licensor grants the licensee the right to transfer, store and process his personal data (full name, scientific degree, academic title, place of work and position, contact information of the authors) with the purpose of including them in the database in accordance with the Law of Ukraine No. 2297 - VI "on protection of personal data" from 01.06.2010.

Personal data and metadata of the article are provided for their storage and processing in various databases and information systems, including them in analytical and statistical reporting, creating sound relationships between the objects of works of science, literature and art with personal data, etc. on unlimited territory. The licensee has the right to transfer the specified data for processing and storage to third parties provided that such a fact is notified with the provision of information about the third party (name and address) to the Licensor.