THE INFLUENCE OF THE CARDIOVASCULAR SYSTEM CONGENITAL PATHOLOGY ON THE KIDNEYS JUXTAGLOMERULAR CELLS DIFFERENTIATION IN CHILDHOOD

Congenital heart defects in children have a significant influence on the state and functions of other body systems, in particular, the urinary system. The kidneys, performing the endocrine function, regulate arterial pressure by the juxtaglomerular apparatus. The aim of the study was to determine the influence of congenital heart defects on the formation of the juxtaglomerular apparatus of the paracortical nephrons in childhood. The objects of the study were of 20 kidney autopsies cases aged from 2 months to 6 years, who were divided into 6 groups by age and the presence or absence of cardiovascular pathologies. The preparations were fixed in neutral 10% formalin, embedded in paraffin, stained with hematoxylin and eosin. Polyclonal primary antibodies to renin were used for immunohistochemical analysis. The sections were used to determine the cross-sectional area of ​​the renal corpuscle, the cross-sectional area of ​​the juxtaglomerular cells, and the degree of renin expression in the juxtavascular cells. The most active growth of the renal corpuscles of the nephrons is observed after 1 year of life, while in patients with cardiovascular malformations, their hypertrophy is noted. The area of ​​the juxtaglomerular cells in the groups without pathologies also increases with age, and in the groups with heart malformations, it increases even more intensively. The revealed dynamics indicate that congenital malformations of the cardiovascular system, causing circulatory disorders, increased blood pressure, involve the juxtaglomerular apparatus of the kidney in the pathogenesis, leading to an increase in the area of ​​rennin-producing cells. Not only the juxtaglomerular cells located in the walls of the afferent arterioles, but also the juxtavascular cells of the vascular glomerulus contribute to the overall level of secreted renin. In early childhood, the area of ​​juxtaglomerular cells increases, while renin expression in juxtavascular cells decreases. In cardiovascular pathology of child, both the area of ​​juxtaglomerular cells and the degree of renin expression by juxtavascular cells increase, which undoubtedly increases the overall level of renin in the body.

1. Zavodnova OS, Kuznetsova IG, Galimova OI. Fizicheskoe razvitie detey s vrozhdennymi porokami razvitiya. Evrazyskiy soyuz uchenykh. 2020;3-3(72):19-24. In Russian

2. Azhar AS, Al Shammasi ZH, Higgi RE. The impact of congenital heart diseases on the quality of life of patients and their families in Saudi Arabia. Biological, psychological, and social dimensions. Saudi Med J. 2016;37(4):392-402. https://doi.org/10.15537/smj.2016.4.13626

3. Cooper DS, Basu RK, Price JF et al. The Kidney in Critical Cardiac Disease: Proceedings. In the 10th International Conference of the Pediatric Cardiac Intensive Care Society. World J Pediatr Congenit Heart Surg. 2016;7(2):152-63. https://doi.org/10.1177/2150135115623289

4. Gist KM, Kwiatkowski DM, Cooper DS. Acute kidney injury in congenital heart disease. Curr Opin Cardiol. 2018;33(1):101-107. https://doi.org/10.1097/HCO.0000000000000473

5. Carlisle MA, Soranno DE, Basu RK, Gist KM. Acute Kidney Injury and Fluid Overload in Pediatric Cardiac Surgery. Curr Treat Options Pediatr. 2019;5(4):326-342. doi:10.1007/s40746-019-00171-6

6. Khuong JN, Wilson TG, Iyengar AJ, d'Udekem Y. Acute and Chronic Kidney Disease Following Congenital Heart Surgery: A Review. Ann Thorac Surg. 2021;112(5):1698-1706. https://doi.org/10.1016/j.athoracsur.2020.10.054

7. Tuegel C, Bansal N. Heart failure in patients with kidney disease. Heart. 2017;103(23):1848-1853. https://doi.org/10.1136/heartjnl-2016-310794

8. Schefold JC, Filippatos G, Hasenfuss G, et al. Heart failure and kidney dysfunction: epidemiology, mechanisms and management. NatRev Nephrol.2016;12(10):610-623. https://doi.org/10.1038/nrneph.2016.113

9. House AA, Wanner C, Sarnak MJ et al. Heart failure in chronic kidney disease: conclusions from a kidney disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2019;95(6):1304-1317. https://doi.org/10.1016/j.kint.2019.02.022

10. Stefekova A, Capkova P, Capkova Z, et al. MLPA analysis of 32 foetuses with a congenital heart defect and 1 foetus with renal defects - pilot study. The significant frequency rate of presented pathological CNV. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2022;166(2):187-194. https://doi.org/10.5507/bp.2021.019

11. Mackenzie HS, Brenner BM. Fewer nephrons at birth A missing link in the etiology of essential hypertension? American Journal of kidney Disease. 1995;26(1):91-98. https://doi.org/10.1016/0272-6386(95)90161-2

12. Ayzman RI. Formirovanie funktsii pochek i vodno-solevogo obmena v ontogeneze. Novye issledovaniya. 2009;3(20):108-112. In Russian

13. Gomez RA. Fate of renin cells during development and disease. Hypertension. 2017;69(3):387-395. https://doi.org/ 10.1161/HYPERTENSIONAHA.116.083

14. Sologub AA, Slesareva EV, Kuznetsova TI, Denisova OF. Otsenka dinamiki razvitiya nefronov u detey s vrozhdennoy patologiey serdechno-sosudistoy sistemy. Izvestiya vysshikh uchebnykh zavedeny. Povolzhsky region. Meditsinskie nauki. 2023;2:116-123. In Russian. https://doi.org/10.21685/2072-3032-2023-2-12

15. Safina AI, Abdullina GA, Daminova MA. Stanovlenie funktsiy pochek u detey, rodivshikhsya prezhdevremenno. Rossyskiy vestnik perinatologii i pediatrii 2016;61(5):166-173. In Russian. https://doi.org/10.21508/1027-4065-2016-61-5-166-173

16. Sequeira Lopez ML, Pents ES, Nomasa T et al. Renin cells are precursors, for multiple cell types that switch to the renin phenotype when homestasis is threatened. Dev. cell. 2004;6:719-728. https://doi.org/10.1016/s1534-5807(04)00134-0

17. 17 Martini AG, Jan Danser AH. Juxtaglomerular cell phenotypic plasticity. High Blood Press Cardiovasc Prev. 2017;24(3):231-242. https://doi.org/10.1007/s40292-017-0212-5

18. Celio MR, Groscurth P, Inagami T. Ontogeny of renin immunoreactive cells in the human kidney. Anat Embryol (Berl). 1985;173(2):149-155. https://doi.org/10.1007/BF00316297

19. Starke C, Betz H, Hickmann L, et al. Renin lineage cells repopulate the glomerular mesangium after injury. J Am Soc Nephrol.2015;26:48-54. doi:10.1681/ASN.2014030265

20. Kon Y. Comparative study of renin-containing cells. Histological approaches. J Vet Med Sci. 1999;61(10):1075-86. https://doi.org/10.1292/jvms.61.1075

21. Lindop GB, Lever AF. Anatomy of the renin-angiotensin system in the normal and pathological kidney. Histopathology. 1986;10(4):335-362. https://doi.org/10.1111/j.1365-2559.1986.tb02489

22. Broeker KAE, Schrankl J, Fuchs MAA, Kurtz A. Flexible and multifaceted: the plasticity of renin-expressing cells. Pflugers Arch. 2022;474(8):799-812. https://doi.org/10.1007/s00424-022-02694-8