TRANSMISSION ELECTRON MICROSCOPY IN THE STUDY OF ULTRASTRUCTURE OF RENAL PARENCHYMA (LITERATURE REVIEW)

DOI: 10.22138/2500-0918-2026-23-1-97-111

A.F. Arslanov¹, G.V. Zubik¹, V.A. Shidin¹, B.A. Berdichevsky²

¹Tyumen State Medical University, Tyumen, Russian Federation;
²Regional Clinical Hospital No. 2 (RCH No. 2), Tyumen, Russian Federation

Abstract. Renal parenchyma, including key elements of the nephron (glomeruli and tubules) together with the surrounding interstitium, is necessary for proper performance of functions including reabsorption, filtration and secretion. The aim of the current literature review is to analyze current studies devoted to the capabilities of TEM in studying the ultrastructure of the renal parenchyma, with a subsequent assessment of the prospects for the development of the method within the framework of an interdisciplinary approach and taking into account modern technological advances. Materials and methods. The literature search was conducted in PubMed, Google scholar, CyberLeninka, eLibrary, using the key terms: «TEM», «ultrastructure», «renal parenchyma», «podocyte», «glomerulus», «tubules», «loops of Henle». Results. Review and analysis of the literature data indicate that a detailed study of the microstructure of the kidneys is fundamental for understanding both normal physiological processes and pathological processes. It follows that transmission electron microscopy (TEM) has become an essential tool in studying the fine structure of the kidney, providing exceptional resolution for precise detailing of the cellular and subcellular components. At the same time, the introduction of modern technologies such as 3D electron microscopy, cryo-electron microscopy and others significantly expand the capabilities of TEM and allow for a deeper study of the kidney ultrastructure. Conclusions. Taking this into account, the use of TEM plays an important role in kidney research, offering new developments in patient management methods based on individual characteristics. Emphasizing the value of TEM in the development of nephrology, this article motivates for continuous innovation in the field of nephrology, as well as interdisciplinary collaboration.

Keywords: kidney, ultrastructure, anatomy, transmission electron microscopy, glomerulus, podocyte, tubules, loops of Henle

There is no conflict of interest.
Contact details of the corresponding author:
Aydar F. Arslanov
aidar_arslanov@mail.ru
Received: 22.04.2025
For citation: Arslanov A.F., Zubik G.V., Shidin V.A., Berdichevsky B.A. Transmission electron microscopy in the study of ultrastructure of renal parenchyma (Literature review) [Online] Vestn. Ural. Med. Akad. Nauki. = Journal of Ural Medical Academic Science. 2026, Vol. 23, no. 1, pp. 97–111. DOI: 10.22138/2500-0918-2026-23-1-97-111 (In Russ)

5. Hoogstraten CA, Hoenderop JG, de Baaij JHF. Mitochondrial Dysfunction in Kidney Tubulopathies. Annu Rev Physiol. 2024 Feb 12;86:379-403. doi: 10.1146/annurev-physiol-042222-025000. Epub 2023 Nov 27. PMID: 380120475. Hoogstraten CA, Hoenderop JG, de Baaij JHF. Mitochondrial Dysfunction in Kidney Tubulopathies. Annu Rev Physiol. 2024 Feb 12;86:379-403. doi: 10.1146/annurev-physiol-042222-025000. Epub 2023 Nov 27. PMID: 38012047
6. Malatesta M. Transmission electron microscopy for nanomedicine: novel applications for long-established techniques. Eur J Histochem. 2016 Dec 9;60(4):2751. doi: 10.4081/ejh.2016.2751. PMID: 28076938; PMCID: PMC5178805
7. Menon MC, Chuang PY, He CJ. The glomerular filtration barrier: components and crosstalk. Int J Nephrol. 2012; 2012:749010. doi: 10.1155/2012/749010. Epub 2012 Aug 14. PMID: 22934182; PMCID: PMC3426247
8. Roy A, Al-bataineh MM, Pastor-Soler NM. Collecting duct intercalated cell function and regulation. Clin J Am Soc Nephrol. 2015 Feb 6;10(2):305-24. doi: 10.2215/CJN.08880914. Epub 2015 Jan 28. PMID: 25632105; PMCID: PMC4317747.
9. Harris JR. Transmission electron microscopy in molecular structural biology: A historical survey. Arch Biochem Biophys. 2015 Sep 1;581:3-18. doi: 10.1016/j.abb.2014.11.011. Epub 2014 Dec 2. PMID: 25475529
10. Malatesta M. Transmission Electron Microscopy as a Powerful Tool to Investigate the Interaction of Nanoparticles with Subcellular Structures. Int J Mol Sci. 2021 Nov 26;22(23):12789. doi: 10.3390/ijms222312789. PMID: 34884592; PMCID: PMC8657944
11. Miyaki T, Homma N, Kawasaki Y, Kishi M, et al. Ultrastructural analysis of whole glomeruli using array tomography. J Cell Sci. 2024 Oct 15;137(20):jcs262154. doi: 10.1242/jcs.262154. Epub 2024 Oct 11. PMID: 39171439
12. Neal CR. Podocytes … What's Under Yours? (Podocytes and Foot Processes and How They Change in Nephropathy). Front Endocrinol (Lausanne). 2015 Feb 23;6:9. doi: 10.3389/fendo.2015.00009. PMID: 25755650; PMCID: PMC4337384
13. Sever S. Role of actin cytoskeleton in podocytes. Pediatr Nephrol. 2021 Sep;36(9):2607-2614. doi: 10.1007/s00467-020-04812-z. Epub 2020 Nov 13. PMID: 33188449; PMCID: PMC8116355
14. Yao Y, Inoki K. The role of mechanistic target of rapamycin in maintenance of glomerular epithelial cells. Curr Opin Nephrol Hypertens. 2016 Jan;25(1):28-34. doi: 10.1097/MNH.0000000000000181. PMID: 26625863; PMCID: PMC4911704.
15. Smirnov A.V., Dobronravov V.A., Sipovsky V.G., Trofimenko I.I., Pirozhkov I.A., Kayukov I.G., Lebedev K.I. Clinical guidelines for diagnosis, treatment and prognosis of minimal change disease in adults. Nephrology. 2014;18(4):68-92.
16. Downie ML, Lopez Garcia SC, Kleta R, Bockenhauer D. Inherited Tubulopathies of the Kidney: Insights from Genetics. Clin J Am Soc Nephrol. 2021 Apr 7;16(4):620-630. doi: 10.2215/CJN.14481119. Epub 2020 Apr 1. Erratum in: Clin J Am Soc Nephrol. 2021 Jul;16(7):1100. doi: 10.2215/CJN.05570421. PMID: 32238367; PMCID: PMC8092065.
17. Curthoys NP, Moe OW. Proximal tubule function and response to acidosis. Clin J Am Soc Nephrol. 2014 Sep 5;9(9):1627-38. doi: 10.2215/CJN.10391012. Epub 2013 Aug 1. PMID: 23908456; PMCID: PMC4152816
18. Zhuo JL, Li XC. Proximal nephron. Compr Physiol. 2013 Jul;3(3):1079-123. doi: 10.1002/cphy.c110061. PMID: 23897681; PMCID: PMC3760239.
19. Bhargava P, Schnellmann RG. Mitochondrial energetics in the kidney. Nat Rev Nephrol. 2017 Oct;13(10):629-646. doi: 10.1038/nrneph.2017.107. Epub 2017 Aug 14. PMID: 28804120; PMCID: PMC5965678
20. Schuh CD, Polesel M, Platonova E, Haenni D, et al. Combined Structural and Functional Imaging of the Kidney Reveals Major Axial Differences in Proximal Tubule Endocytosis. J Am Soc Nephrol. 2018 Nov; 29(11):2696-2712. doi: 10.1681/ASN.2018050522. Epub 2018 Oct 9. PMID: 30301861; PMCID: PMC6218873
21. Šárka Lhoták, Sudesh Sood, Elise Brimble, Rachel E. et al. ER stress contributes to renal proximal tubule injury by increasing SREBP-2-mediated lipid accumulation and apoptotic cell death. American Journal of Physiology-Renal Physiology, 2012; 303:2, F266-F278 https://doi.org/10.1152/ajprenal.00482.2011
22. I. M. Larina, L. Kh. Pastushkova, K. S. Kireev, A. I. Grigoriev. Formation of the urine proteome in healthy humans. Human Physiology – 2013. – Vol. 39, No. 2. – P. 43. – DOI 10.7868/S0131164613020070. – EDN PWNECX.
23. Christensen EI, Gburek J. Protein reabsorption in renal proximal tubule-function and dysfunction in kidney pathophysiology. Pediatr Nephrol. 2004 Jul;19(7):714-21. doi: 10.1007/s00467-004-1494-0. Epub 2004 May 14. PMID: 15146321.
24. Nielsen R, Christensen EI, Birn H. Megalin and cubilin in proximal tubule protein reabsorption: from experimental models to human disease. Kidney Int. 2016 Jan;89(1):58-67. doi: 10.1016/j.kint.2015.11.007. PMID: 26759048.
25. Rbaibi Y, Long KR, Shipman KE, Ren Q, Baty CJ, Kashlan OB, Weisz OA. Megalin, cubilin, and Dab2 drive endocytic flux in kidney proximal tubule cells. Mol Biol Cell. 2023 Jun 1;34(7):ar74. doi: 10.1091/mbc.E22-11-0510. Epub 2023 Apr 26. PMID: 37126375; PMCID: PMC10295476.
26. Molitoris BA, Sandoval RM, Yadav SPS, Wagner MC. Albumin uptake and processing by the proximal tubule: physiological, pathological, and therapeutic implications. Physiol Rev. 2022 Oct 1;102(4):1625-1667. doi: 10.1152/physrev.00014.2021. Epub 2022 Apr 4. PMID: 35378997; PMCID: PMC9255719.
27. Wagner MC, Myslinski J, Pratap S, Flores B, Rhodes G, Campos-Bilderback SB, Sandoval RM, Kumar S, Patel M, Ashish, Molitoris BA. Mechanism of increased clearance of glycated albumin by proximal tubule cells. Am J Physiol Renal Physiol. 2016 May 1;310(10):F1089-102. doi: 10.1152/ajprenal.00605.2015. Epub 2016 Feb 17. PMID: 26887834; PMCID: PMC4889321.
28. Lebedeva Elena Nikolaevna, Vylkova Albina Alexandrovna, Afonina Svetlana Nikolaevna, Chesnakova Svetlana Alexandrovna. Dyslipidemia as a pathogenetic factor in the progression of chronic kidney disease. Nephrology (Russia). 2019. No. 5. URL: https://cyberleninka.ru/article/n/dislipidemiya-kak-patogeneticheskiy-faktor-progressirovaniya-hronicheskoy-bolezni-pochek (accessed: 15.06.2025).
29. Mironova, N. V. Diagnostics of renal concentration function: new possibilities. RMZh. — 2010. — Vol. 18, No. 30. — P. 1820-1823. — EDN PYSDAT29.
30. Popov Sergey Valerievich, Guseinov Ruslan Guseinovich, Gorshenin Andrey Nikolaevich, Sivak Konstantin Vladimirovich, et al. Changes in the ultrastructural organization of the kidney under conditions of experimentally modeled thermal ischemia during surgery. Bulletin of St. Petersburg University. Medicine. 2016. No. 1. URL: https://cyberleninka.ru/article/n/izmeneniya-ultrastrukturnoy-organizatsii-pochki-v-usloviyah-eksperimentalno-smodelirovannoy-teplovoy-ishemii-pri-operativnom(date of access: 11.06.2025).
31. Marchenko, D. S. Results of morphological study of the kidneys in experimental hypothyroidism. Biodiversity, bioresources, biotechnology issues and health of the population of the North Caucasus region: Proceedings of the VII (64th) annual scientific and practical conference «University Science — to the Region» of the North Caucasus Federal University, Stavropol, April 3-29, 2019. — Stavropol: North Caucasus Federal University, 2019. — P. 303-307. — EDN MEZMMN.
32. Kumaran GK, Hanukoglu I. Identification and classification of epithelial cells in nephron segments by actin cytoskeleton patterns. FEBS J. 2020 Mar;287(6):1176-1194. doi: 10.1111/febs.15088. Epub 2019 Nov 1. PMID: 31605441; PMCID: PMC7384063.
33. Mount DB. Thick ascending limb of the loop of Henle. Clin J Am Soc Nephrol. 2014 Nov 7;9(11):1974-86. doi: 10.2215/CJN.04480413. Epub 2014 Oct 15. PMID: 25318757; PMCID: PMC4220766.
34. Zacchia M, Capolongo G, Rinaldi L, Capasso G. The importance of the thick ascending limb of Henle's loop in renal physiology and pathophysiology. Int J Nephrol Renovasc Dis. 2018 Feb 15;11:81-92. doi: 10.2147/IJNRD.S154000. PMID: 29497325; PMCID: PMC5818843.
35. Popov S. V., Ulitina A. S., Guseinov R. G., Sivak K. V., Perepelitsa V. V., Nadein K. A., Bunenkov N. S. The role of epigenetic factors in the pathogenesis of urolithiasis: focus on the claudin-mikrornk system. Medical Bulletin of Bashkortostan. 2023. No. 1 (103). URL: https://cyberleninka.ru/article/n/rol-epigeneticheskih-faktorov-v-patogeneze-mochekamennoy-bolezni-fokus-na-sistemu-klaudiny-mikrornk (accessed: 15.06.2025).
36. Saito AC, Higashi T, Fukazawa Y, Otani T, Tauchi M, Higashi AY, Furuse M, Chiba H. Occludin and tricellulin facilitate formation of anastomosing tight-junction strand network to improve barrier function. Mol Biol Cell. 2021 Apr 15;32(8):722-738. doi: 10.1091/mbc.E20-07-0464. Epub 2021 Feb 10. PMID: 33566640; PMCID: PMC8108510.
37. Marcoux AA, Tremblay LE, Slimani S, Fiola MJ, Mac-Way F, Garneau AP, Isenring P. Molecular characteristics and physiological roles of Na+ -K+ -Cl- cotransporter 2. J Cell Physiol. 2021 Mar;236(3):1712-1729. doi: 10.1002/jcp.29997. Epub 2020 Aug 10. PMID: 32776569; PMCID: PMC7818487
38. Edwards A, McDonough AA, Ellison DH. Flow-dependent transport processes 2024: filtration, absorption, and secretion. Am J Physiol Renal Physiol. 2025 May 1;328(5):F627-F637. doi: 10.1152/ajprenal.00303.2024. Epub 2025 Mar 17. PMID: 40094947; PMCID: PMC12053844.
39. Rao R, Bhalla V, Pastor-Soler NM. Intercalated Cells of the Kidney Collecting Duct in Kidney Physiology. Semin Nephrol. 2019 Jul;39(4):353-367. doi: 10.1016/j.semnephrol.2019.04.005. PMID: 31300091; PMCID: PMC6629462
40. Sologub A.A., Slesareva E.V., Kuznetsova T.I., Smirnova E.V. Analysis of the development of the juxtaglomerular apparatus of the kidneys in childhood. Modern Problems of Science and Education. 2022. No. 2.; URL: https://science-education.ru/ru/article/view?id=31613 (date of access: 11.06.2025). DOI: https://doi.org/10.17513/spno.31613
41. Aidarbekova Zifargul Musulmankulova, Makhmudova Zhyldyz Akhmatovna, Aidarbekova Aizhan, Kalugina Olga Petrovna Changes in electron microscopy of kidney nephrons, their mitotic activity in acute massive blood loss in high-altitude conditions in unadapted and adapted animals. Bulletin of Science and Education. 2019. No. 20-2 (74). URL: https://cyberleninka.ru/article/n/izmeneniya-elektronnoy-mikroskopii-nefronov-pochek-ih-mitoticheskoy-aktivnosti-pri-ostroy-massivnoykrovopotere-v-usloviyah (date of access: 15.06.2025).
42. Armin Kurtz. Commentary for “human kidney pericytes produce renin”. Kidney International. 2016; 90(6): 1153-1154. https://doi.org/10.1016/j.kint.2016.08.018.
43. Baimukhambetov Renat Kuspanovich, Vishnevskaya Tatyana Yakovlevna Ultrastructural organization of the kidney of adult sheep of the south ural breed. Bulletin of the OGAU. 2023. No. 2 (100). URL: https://cyberleninka.ru/article/n/ultrastrukturnaya-organizatsiya-pochki-vzrosloy-ovtsy-yuzhnouralskoy-porody (date of access: 15.06.2025).
44. Gyarmati G, Shroff UN, Riquier-Brison A, Kriz W, Kaissling B, Neal CR, Arkill KP, Ahmadi N, Gill IS, Moon JY, Desposito D, Peti-Peterdi J. A new view of macula densa cell microanatomy. Am J Physiol Renal Physiol. 2021 Mar 1;320(3):F492-F504. doi: 10.1152/ajprenal.00546.2020. Epub 2021 Jan 25. PMID: 33491562; PMCID: PMC7988809.
45. Lorenzi T, Graciotti L, Sagrati A, et al. Normal human macula densa morphology and cell turnover: A histological, ultrastructural, and immunohistochemical investigation. Anat Rec. 2020; 303: 2904–2916. https://doi.org/10.1002/ar.24465
46. Blankenstein KI, Borschewski A, Labes R, Paliege A, Boldt C, McCormick JA, Ellison DH, Bader M, Bachmann S, Mutig K. Calcineurin inhibitor cyclosporine A activates renal Na-K-Cl cotransporters via local and systemic mechanisms. Am J Physiol Renal Physiol. 2017 Mar 1;312(3):F489-F501. doi: 10.1152/ajprenal.00575.2016. Epub 2016 Dec 21. PMID: 28003191; PMCID: PMC5504423.
47. Castrop H, Schnermann J. Isoforms of renal Na-K-2Cl cotransporter NKCC2: expression and functional significance. Am J Physiol Renal Physiol. 2008 Oct;295(4):F859-66. doi: 10.1152/ajprenal.00106.2008. Epub 2008 May 21. PMID: 18495801; PMCID: PMC2576146.
48. Taugner R, Schiller A, Kaissling B, Kriz W. Gap junctional coupling between the JGA and the glomerular tuft. Cell Tissue Res. 1978 Jan 17;186(2):279-85. doi: 10.1007/BF00225537. PMID: 627020.
49. Unnersjö-Jess D, Scott L, Sevilla SZ, Patrakka J, Blom H, Brismar H. Confocal super-resolution imaging of the glomerular filtration barrier enabled by tissue expansion. Kidney Int. 2018 Apr;93(4):1008-1013. doi: 10.1016/j.kint.2017.09.019. Epub 2017 Dec 11. PMID: 29241621
50. Peddie CJ, Collinson LM. Exploring the third dimension: volume electron microscopy comes of age. Micron. 2014 Jun; 61:9-19. doi:10.1016/j.micron.2014.01.009. Epub 2014 Feb 12. PMID: 24792442
51. Bohman SO. The ultrastructure of the renal interstitium. Contemp Issues Nephrol. 1979;9:1-34.
52. Breyer MD, Breyer RM. Prostaglandin E receptors and the kidney. Am J Physiol Renal Physiol. 2018;279(1):F12-F23. doi: 10.1152/ajprenal.2018.279.1.F12.
53. Hao CM, Breyer MD. Physiological regulation of prostaglandins in the kidney. Annu Rev Physiol. 2019;81:517-538. doi: 10.1146/annurev-physiol-020518-114656.
54. Balzer MS, Rohacs T, Susztak K. Single-cell analysis of human proximal tubules reveals altered lipid metabolism in chronic kidney disease. J Am Soc Nephrol. 2022;33(5):912-928. doi: 10.1681/ASN.2021091234.
55. Zhong F, Chen H, Xie Y, et al. mPGES-2 blockade attenuates podocyte injury and tubulointerstitial fibrosis in diabetic kidney disease by reducing lipid accumulation. Kidney Int. 2024;105(2):345-360. doi: 10.1016/j.kint.2023.11.022.
56. Honda K, Takaki T, Kang D. Recent advances in electron microscopy for the diagnosis and research of glomerular diseases. Kidney Res Clin Pract. 2023 Mar;42(2):155-165. doi: 10.23876/j.krcp.21.270. Epub 2022 May 4. PMID: 35545227; PMCID: PMC10085717
57. Thompson RF, Walker M, Siebert CA, Muench SP, Ranson NA. An introduction to sample preparation and imaging by cryo-electron microscopy for structural biology. Methods. 2016 May 1;100:3-15. doi: 10.1016/j.ymeth.2016.02.017. Epub 2016 Feb 28. PMID: 26931652; PMCID: PMC4854231

Authors
Aydar F. Arslanov
Federal State Budgetary Educational Institution of Higher Education «Tyumen State Medical University»
Postgraduate student, Department of Histology and Cell Biology, Tyumen State Medical University
Tyumen, Russian Federation
aidar_arslanov@mail.ru
ORCID: https: // 0009-0004-3050-2324
Grigory V. Zubik
Federal State Budgetary Educational Institution of Higher Education «Tyumen State Medical University» of the Ministry of Health of the Russian Federation
Student, Institute of Clinical Medicine, Tyumen State Medical University
Tyumen, Russian Federation
Email: grisha.zubik@mail.ru
ORCID: 0009-0005-1333-2922
SPIN-code: 9388-0941

Vladimir A. Shidin
Federal State Budgetary Educational Institution of Higher Education «Tyumen State Medical University» of the Ministry of Health of the Russian Federation
Doctor of Medical Sciences, Associate Professor, Head of the Department of Histology and Cell Biology, Tyumen State Medical University
Tyumen, Russian Federation
Email: vshidin@mail.ru
ORCID: 0000-0003-1396-5381
elibrary SPIN: 5431-1510

Boris A. Berdichevsky
State Budgetary Healthcare Institution of the Tyumen Region «Regional Clinical Hospital No.2»
Doctor of Medical Sciences, Professor, Professor of the Department of Surgery and Urology with a Course in Endoscopy, Tyumen State Medical University
Tyumen, Russian Federation
Email: doktor_bba@mail.ru
ORCID: 0000-0002-9414-8510
elibrary SPIN: 4630-3855