Metabolic disorders and androgen deficiency in the pathogenesis of urolithiasis

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

This review summarizes and critically analyzes current data on the pathogenesis of urolithiasis (urolithiasis, nephrolithiasis). Emphasis is placed on such issues as: mechanisms of urinary stone formation; risk factors for stone formation; the role of oxidative stress; the chemical composition of renal stones (and especially oxalates); the role of Randall’s plaques, osteopontin, uromodulin (Tamm–Horsfall protein), α-enolase; and the mechanism of stone formation in the collecting ducts. Insufficiently studied issues of microbiota influence — (a) kidney and urinary tract and (b) gastrointestinal tract are also considered. Attention is paid to new approaches to understanding the pathogenesis and treatment of urolithiasis, namely works on genetics, epigenetics, genetic engineering and proteomics. The imperfection of existing animal models of urolithiasis is shown. The issue of application of androgen replacement therapy in the treatment of patients suffering from urolithiasis is considered separately. The author considers the main theoretical result of his work to be the approval of the idea of urolithiasis as a systemic disease, in which any significant deviation of the internal environment constants violates the delicate balance that ensures the solubility of substances in primary urine and their excretion with secondary urine. The practical result is to confirm the applicability of androgen replacement therapy in the treatment of patients suffering from urolithiasis.

Full Text

Restricted Access

About the authors

Zaur K. Emirgaev

Saint Petersburg State Pediatric Medical University

Email: zzemir@mail.ru
SPIN-code: 6771-7532

Postgraduate Student, Pathophysiology Department

Russian Federation, 2 Litovskaya str., Saint Petersburg, 194100

Ruslan N. Tagirov

Saint Petersburg State Pediatric Medical University

Email: avas7@mail.ru

Student

Russian Federation, 2 Litovskaya str., Saint Petersburg, 194100

Nair S. Tagirov

Saint Petersburg State Pediatric Medical University

Email: ruslana73nair@mail.ru
ORCID iD: 0000-0002-4362-3369
SPIN-code: 9810-1650

MD, PhD, Dr. Sci. (Medicine), Professor, Pathophysiology Department

Russian Federation, 2 Litovskaya str., Saint Petersburg, 194100

Andrei G. Vasiliev

Saint Petersburg State Pediatric Medical University

Author for correspondence.
Email: avas7@mail.ru
ORCID iD: 0000-0002-8539-7128
SPIN-code: 1985-4025
Scopus Author ID: 56496365400
ResearcherId: F-8743-2017
https://www.gpmu.org/eng/university_eng/departments/Pathological_physiology/Vasiliev/

MD, PhD, Dr. Sci. (Medicine), Professor, Head of Pathophysiology Department

Russian Federation, 2 Litovskaya str., Saint Petersburg, 194100

Ruslan N. Tagirov

Saint Petersburg State Pediatric Medical University

Email: avas7@mail.ru
ORCID iD: 0009-0002-9375-4364

Student

Russian Federation, 2 Litovskaya str., Saint Petersburg, 194100

References

  1. Anichkova IV, Arkhipov VV, Benameño JP, et al. Clinical pediatric nephrology. Saint Petersburg: Sotis; 1997. 717 p. EDN: VRKSMB
  2. Apolikhin OI, Sivkov AV, Solntseva TV, Komarova VA. Analysis of urological morbidity in the Russian Federation within the period of 2005–2010. Experimental and Clinic Urology. 2012(2):64–72. EDN: PDARKJ
  3. Gadzhiev NK, Malkhasyan VA, Mazurenko DV, et al. Urolithiasis and metabolic syndrome. Pathophysiology of stone formation. Experimental & Clinical Urology. 2018;(1):66–75. EDN: WCZJLF
  4. Nazarov TH, Guliev BG, Stetsik OV, et al. Diagnostics and correction of metabolic disorders in patients with recurrent urolithiasis after endoscopic removal of stones. Andrology and Genital Surgery. 2015;16(3):22–28. EDN: ULHBXH doi: 10.17650/2070-9781-2015-16-3-22-28
  5. Nitkin DM. Predictors of recurrent urolithiasis in patients with age-related androgenic disorders. Medical News. 2017;(11):53–56. EDN: XGLPPA
  6. Smirnova NN, Kuprienko NB. Uromodulin and its role in the formation of renal components in children and adolescents. Children’s Medicine of the North-West. 2022;10(1):44–48.
  7. Tagirov NS, Trashkov AP, Balashov LD, Balashov NA. The role of androgenous deficiency in the development of urolitiasis in experimental ethylenglycol rat model. Pediatrician (St. Petersburg). 2015;6(3):86–90. doi: 10.17816/PED6386-90
  8. Tagirov NS. Pathogenetic correction of metabolic disorders and androgen deficiency in the treatment of patients with urolithiasis (clinical and experimental study) [Dissertation]. Saint Petersburg; 2019. 256 p. (In Russ.) Available from: https://vmeda.mil.ru/upload/site56/document_file/h5OPaCxTzp.pdf
  9. Trashkov AP, Vasiliev AG, Kovalenko AD, Tagirov NS. Metabolic therapy of nephrolithiasis in two different rat models of kidney disease. Éksperimentalnaya i Klinicheskaya Farmakologiya. 2015;78(3):17–21. EDN: TNJRKB
  10. Shuster PI, Glybochko PV. Condition of lithogenesis processes in kidneys secondary to androgynous therapies lithogenesis processes in kidneys at receiving androgynous therapy. Saratov Journal of Medical Scientific Research. 2009;5(4):612–615. EDN: KXWZOF
  11. Aggarwal KP, Narula S, Kakkar M, Tandon C. Nephrolithiasis: molecular mechanism of renal stone formation and the critical role played by modulators. Biomed Res Int. 2013;2013:292953. doi: 10.1155/2013/292953
  12. Akagi S, Sugiyama H, Makino H. [Infection and chronic kidney disease]. Nihon Rinsho. 2008;66(9):1794–1798. (In Japanese).
  13. Al KF, Daisley BA, Chanyi RM, Bjazevic J, et al. Oxalate-degrading bacillus subtilis mitigates urolithiasis in a drosophila melanogaster model. mSphere. 2020;5(5):e00498–e00420. doi: 10.1128/mSphere.00498-20
  14. Alelign T, Petros B. Kidney stone disease: an update on current concepts. Adv Urol. 2018;2018:3068365. doi: 10.1155/2018/3068365
  15. Alshehri M, Alsaeed H, Alrowili M, et al. Evaluation of risk factors for recurrent renal stone formation among Saudi Arabian patients: Comparison with first renal stone episode. Arch Ital Urol Androl. 2023;95(3):11361. doi: 10.4081/aiua.2023.11361
  16. Arcidiacono T, Mingione A, Macrina L, et al. Idiopathic calcium nephrolithiasis: a review of pathogenic mechanisms in the light of genetic studies. Am J Nephrol. 2014;40(6):499–506. doi: 10.1159/000369833
  17. Bagga HS, Chi T, Miller J, Stoller ML. New insights into the pathogenesis of renal calculi. Urol Clin North Am. 2013;40(1):1–12. doi: 10.1016/j.ucl.2012.09.006
  18. D’Ambrosio V, Ferraro PM, Lombardi G, et al. Unravelling the complex relationship between diet and nephrolithiasis: the role of nutrigenomics and nutrigenetics. Nutrients. 2022;14(23):4961. doi: 10.3390/nu14234961
  19. Chaiyarit S, Thongboonkerd V. Mitochondrial dysfunction and kidney stone disease. Front Physiol. 2020;11:566506. doi: 10.3389/fphys.2020.566506
  20. Changtong C, Peerapen P, Khamchun S, et al. In vitro evidence of the promoting effect of testosterone in kidney stone disease: A proteomics approach and functional validation. J Proteomics. 2016;144:11–22. doi: 10.1016/j.jprot.2016.05.028
  21. Chung HJ. The role of Randall plaques on kidney stone formation. Transl Androl Urol. 2014;3(3):251–254. doi: 10.3978/j.issn.2223-4683.2014.07.03
  22. Coe FL, Worcester EM, Evan AP. Idiopathic hypercalciuria and formation of calcium renal stones. Nat Rev Nephrol. 2016;12(9): 519–533. doi: 10.1038/nrneph.2016.101
  23. Daudon M, Bouzidi H, Bazin D. Composition and morphology of phosphate stones and their relation with etiology. Urological Research. 2010;38(6):459–467. doi: 10.1007/s00240-010-0320-3
  24. Emami E, Heidari-Soureshjani S, Oroojeni Mohammadjavad A, Sherwin CM. Obesity and the risk of developing kidney stones: a systematic review and meta-analysis. Iran J Kidney Dis. 2023;1(2):63–72.
  25. Ermer T, Nazzal L, Tio MC, et al. Oxalate homeostasis. Nat Rev Nephrol. 2023;19(2):123–138. doi: 10.1038/s41581-022-00643-3
  26. Espinosa-Ortiz EJ, Eisner BH, Lange D, Gerlach R. Current insights into the mechanisms and management of infection stones. Nat Rev Urol. 2019;16(1):35–53. doi: 10.1038/s41585-018-0120-z
  27. Evan A, Lingeman J, Coe FL, Worcester E. Randall’s plaque: pathogenesis and role in calcium oxalate nephrolithiasis. Kidney Int. 2006;69(8):1313–1318. doi: 10.1038/sj.ki.5000238
  28. Evan AP, Worcester EM, Coe FL, et al. Mechanisms of human kidney stone formation. Urolithiasis. 2015;43(S1):19–32. doi: 10.1007/s00240-014-0701-0
  29. Fuster DG, Morard GA, Schneider L, et al. Association of urinary sex steroid hormones with urinary calcium, oxalate and citrate excretion in kidney stone formers. Nephrol Dial Transplant. 2022;37(2):335–348. doi: 10.1093/ndt/gfaa360
  30. Gao H, Lin J, Xiong F, Yu Z, et al. Urinary microbial and metabolomic profiles in kidney stone disease. Front Cell Infect Microbiol. 2022;12:953392. doi: 10.3389/fcimb.2022.953392
  31. Gianmoena K, Gasparoni N, Jashari A, et al. Epigenomic and transcriptional profiling identifies impaired glyoxylate detoxification in NAFLD as a risk factor for hyperoxaluria. Cell Rep. 2021;36(8):109526. doi: 10.1016/j.celrep.2021.109526
  32. Gupta K, Gill GS, Mahajan R. Possible role of elevated serum testosterone in pathogenesis of renal stone formation. Int J Appl Basic Med Res. 2016;6(4):241–244. doi: 10.4103/2229–516X.192593
  33. Hamano S, Nakatsu H, Suzuki N, et al. Kidney stone disease and risk factors for coronary heart disease. Int J Urol. 2005;12(10): 859–863. doi: 10.1111/j.1442-2042.2005.01160.x
  34. Hsi RS, Ramaswamy K, Ho SP, Stoller ML. The origins of urinary stone disease: upstream mineral formations initiate downstream Randall’s plaque. BJU Int. 2017;119(1):177–184. doi: 10.1111/bju.13555
  35. Jeong JY, Oh KJ, Sohn JS, et al. Clinical course and mutational analysis of patients with cystine stone: a single-center experience. Biomedicines. 2023;11(10):2747. doi: 10.3390/biomedicines11102747
  36. Jung HD, Cho S, Lee JY. Update on the effect of the urinary microbiome on urolithiasis. Diagnostics (Basel). 2023;13(5):951. doi: 10.3390/diagnostics13050951
  37. Khan SR. Is oxidative stress, a link between nephrolithiasis and obesity, hypertension, diabetes, chronic kidney disease, metabolic syndrome? Urol Res. 2012;40(2):95–112. doi: 10.1007/s00240-011-0448-9
  38. Khan SR. Reactive oxygen species as the molecular modulators of calcium oxalate kidney stone formation: evidence from clinical and experimental investigations. J Urol. 2013;189(3):803–811. doi: 10.1016/j.juro.2012.05.078
  39. Khan SR, Pearle MS, Robertson WG, et al. Kidney stones. Nat Rev Dis Primers. 2016;2:16008. doi: 10.1038/nrdp.2016.8
  40. Khan SR. Histological aspects of the “fixed-particle” model of stone formation: animal studies. Urolithiasis. 2017;45(1):75–87. doi: 10.1007/s00240-016-0949-7
  41. Khan SR, Canales BK. Proposal for pathogenesis-based treatment options to reduce calcium oxalate stone recurrence. Asian J Urol. 2023;10(3):246–257. doi: 10.1016/j.ajur.2023.01.008
  42. Khandrika L, Koul S, Meacham RB, Koul HK. Kidney injury molecule-1 is up-regulated in renal epithelial cells in response to oxalate in vitro and in renal tissues in response to hyperoxaluria in vivo. PLoS One. 2012;7(9): e44174. doi: 10.1371/journal.pone.0044174. Retraction in: PLoS One. 2020;15(6): e0234862
  43. Liang L, Li L, Tian J, et al. Androgen receptor enhances kidney stone-CaOx crystal formation via modulation of oxalate biosynthesis & oxidative stress. Mol Endocrinol. 2014;28(8):1291–1303. doi: 10.1210/me.2014-1047
  44. Liu Y, Jin X, Tian L et al. Lactiplantibacillus plantarum reduced renal calcium oxalate stones by regulating arginine metabolism in gut microbiota. Front Microbiol. 2021;12:743097. doi: 10.3389/fmicb.2021.743097
  45. Matsuura K, Maehara N, Hirota A, et al. Two independent modes of kidney stone suppression achieved by AIM/CD5L and KIM-1. Commun Biol. 2022;5(1):783. doi: 10.1038/s42003-022-03750-w
  46. Mehta M, Goldfarb DS, Nazzal L. The role of the microbiome in kidney stone formation. Int J Surg. 2016;36(Pt D):607–612. doi: 10.1016/j.ijsu.2016.11.024
  47. Messa P, Castellano G, Vettoretti S, et al. Vitamin D and calcium supplementation and urolithiasis: a controversial and multifaceted relationship. Nutrients. 2023;15(7):1724. doi: 10.3390/nu15071724
  48. Nikolic-Paterson DJ, Wang S, Lan HY. Macrophages promote renal fibrosis through direct and indirect mechanisms. Kidney Int Suppl (2011). 2014;4(1):34–38. doi: 10.1038/kisup.2014.7
  49. O’Kell AL, Grant DC, Khan SR. Pathogenesis of calcium oxalate urinary stone disease: species comparison of humans, dogs, and cats. Urolithiasis. 2017;45(4):329–336. doi: 10.1007/s00240-017-0978-x
  50. Olvera-Posada D, Dayarathna T, Dion M, et al. Kim-1 is a potential urinary biomarker of obstruction: results from a prospective cohort study. J Endourol. 2017;31(2):111–118. doi: 10.1089/end.2016.0215
  51. Patel M, Yarlagadda V, Adedoyin O, et al. Oxalate induces mitochondrial dysfunction and disrupts redox homeostasis in a human monocyte derived cell line. Redox Biol. 2018;15:207–215. doi: 10.1016/j.redox.2017.12.003
  52. Peerapen P, Thongboonkerd V. Protective cellular mechanism of estrogen against kidney stone formation: a proteomics approach and functional validation. Proteomics. 2019;19(19):e1900095. doi: 10.1002/pmic.201900095
  53. Peerapen P, Thongboonkerd V. Protein network analysis and functional enrichment via computational biotechnology unravel molecular and pathogenic mechanisms of kidney stone disease. Biomed J. 2023;46(2):100577. doi: 10.1016/j.bj.2023.01.001
  54. Peng Y, Fang Z, Liu M, et al. Testosterone induces renal tubular epithelial cell death through the HIF-1α/BNIP3 pathway. J Transl Med. 2019;17(1):62. doi: 10.1186/s12967-019-1821-7 Erratum in: J Transl Med. 2021;19(1):146.
  55. Peng Y, Fang Z, Liu M, et al. Correction to: Testosterone induces renal tubular epithelial cell death through the HIF-1α/BNIP3 pathway. J Transl Med. 2021;19(1):146. doi: 10.1186/s12967-021-02799-1 Erratum in: J Transl Med. 2019;17(1):62.
  56. Randall A. The origin and growth of renal calculi. Ann Surg. 1937;105(6):1009–1027. doi: 10.1097/00000658-193706000-00014
  57. Rivera M, Jaeger C, Yelfimov D, Krambeck AE. Risk of chronic kidney disease in brushite stone formers compared with idiopathic calcium oxalate stone formers. Urology. 2017;99:23–26. doi: 10.1016/j.urology.2016.08.041
  58. Sakhaee K. Recent advances in the pathophysiology of nephrolithiasis. Kidney Int. 2009;75(6):585–595. doi: 10.1038/ki.2008.626
  59. Shimshilashvili L, Aharon S, Moe OW, Ohana E. Novel human polymorphisms define a key role for the SLC26A6-stas domain in protection from Ca2+-oxalate lithogenesis. Front Pharmacol. 2020;11:405. doi: 10.3389/fphar.2020.00405
  60. Sinha SK, Mellody M, Carpio MB, et al. Osteopontin as a biomarker in chronic kidney disease. Biomedicines. 2023;11(5):1356. doi: 10.3390/biomedicines11051356
  61. Siener R, Bangen U, Sidhu H, et al. The role of Oxalobacter formigenes colonization in calcium oxalate stone disease. Kidney Int. 2013;83(6):1144–1149. doi: 10.1038/ki.2013.104
  62. Spatola L, Ferraro PM, Gambaro G, et al. Metabolic syndrome and uric acid nephrolithiasis: insulin resistance in focus. Metabolism. 2018;83:225–233. doi: 10.1016/j.metabol.2018.02.008
  63. Sueksakit K, Thongboonkerd V. Protective effects of finasteride against testosterone-induced calcium oxalate crystallization and crystal-cell adhesion. J Biol Inorg Chem. 2019;24(7):973–983. doi: 10.1007/s00775-019-01692-z
  64. Thielemans R, Speeckaert R, Delrue C, et al. Unveiling the hidden power of uromodulin: a promising potential biomarker for kidney diseases. Diagnostics (Basel). 2023;13(19):3077. doi: 10.3390/diagnostics13193077
  65. Tian L, Liu Y, Xu X, et al. Lactiplantibacillus plantarum J-15 reduced calcium oxalate kidney stones by regulating intestinal microbiota, metabolism, and inflammation in rats. FASEB J. 2022;36(6): e22340. doi: 10.1096/fj.202101972RR
  66. Veena CK, Josephine A, Preetha SP, et al. Mitochondrial dysfunction in an animal model of hyperoxaluria: a prophylactic approach with fucoidan. Eur J Pharmacol. 2008;579(1–3):330–336. doi: 10.1016/j.ejphar.2007.09.044
  67. Wang J, Wang W, Wang H, Tuo B. Physiological and pathological functions of SLC26A6. Front Med (Lausanne). 2021;7:618256. doi: 10.3389/fmed.2020.618256
  68. Wang Z, Zhang Y, Zhang J, et al. Recent advances on the mechanisms of kidney stone formation (Review). Int J Mol Med. 2021;48(2):149. doi: 10.3892/ijmm.2021.4982
  69. Wei Z, Cui Y, Tian L, et al. Probiotic Lactiplantibacillus plantarum N-1 could prevent ethylene glycol-induced kidney stones by regulating gut microbiota and enhancing intestinal barrier function. FASEB J. 2021;35(11): e21937. doi: 10.1096/fj.202100887RR
  70. Williams JC Jr, Worcester E, Lingeman JE. What can the microstructure of stones tell us? Urolithiasis. 2017;45(1):19–25. doi: 10.1007/s00240-016-0944-z
  71. Wong YV, Cook P, Somani BK. The association of metabolic syndrome and urolithiasis. Int J Endocrinol. 2015;2015:570674. doi: 10.1155/2015/570674
  72. Woodard LE, Welch RC, Veach RA, et al. Metabolic consequences of cystinuria. BMC Nephrol. 2019;20(1):227. doi: 10.1186/s12882-019-1417-8
  73. Wu XR. Interstitial calcinosis in renal papillae of genetically engineered mouse models: relation to Randall’s plaques. Urolithiasis. 2015;43 Suppl. 1(01):65–76. doi: 10.1007/s00240-014-0699-3
  74. Xiaoran Li X, Chen S, Feng D, et al. Calcium-sensing receptor promotes calcium oxalate crystal adhesion and renal injury in Wistar rats by promoting ROS production and subsequent regulation of PS ectropion, OPN, KIM-1, and ERK expression. Ren Fail. 2021;43(1):465–476. doi: 10.1080/0886022X.2021.1881554
  75. Xu Z, Yao X, Duan C, et al. Metabolic changes in kidney stone disease. Front Immunol. 2023;14:1142207. doi: 10.3389/fimmu.2023.1142207
  76. Yagisawa T, Ito F, Osaka Y, et al. The influence of sex hormones on renal osteopontin expression and urinary constituents in experimental urolithiasis. J Urol. 2001;166(3):1078–1082.
  77. Ye Z, Zeng G, Yang H, et al. The status and characteristics of urinary stone composition in China. BJU Int. 2020;125(6):801–809. doi: 10.1111/bju.14765
  78. Yoodee S, Thongboonkerd V. Bioinformatics and computational analyses of kidney stone modulatory proteins lead to solid experimental evidence and therapeutic potential. Biomed Pharmacother. 2023;159:114217. doi: 10.1016/j.biopha.2023.114217
  79. Yuan P, Sun X, Liu X, et al. Kaempferol alleviates calcium oxalate crystal-induced renal injury and crystal deposition via regulation of the AR/NOX2 signaling pathway. Phytomedicine. 2021;86:153555. doi: 10.1016/j.phymed.2021.153555
  80. Zee T, Bose N, Zee J, et al. α-Lipoic acid treatment prevents cystine urolithiasis in a mouse model of cystinuria. Nat Med. 2017;23(3):288–290. doi: 10.1038/nm.4280
  81. Zeng G, Mai Z, Xia S, et al. Prevalence of kidney stones in China: an ultrasonography based cross-sectional study. BJU Int. 2017;120(1):109–116. doi: 10.1111/bju.13828
  82. Zhao C, Yang H, Zhu X, et al. Oxalate-degrading enzyme recombined lactic acid bacteria strains reduce hyperoxaluria. Urology. 2018;113:253.e1–253.e7. doi: 10.1016/j.urology.2017.11.038
  83. Zhu W, Zhao Z, Chou FJ, et al. The protective roles of estrogen receptor β in renal calcium oxalate crystal formation via reducing the liver oxalate biosynthesis and renal oxidative stress-mediated cell injury. Oxid Med Cell Longev. 2019;2019:5305014. doi: 10.1155/2019/5305014

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Eco-Vector


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 69634 от 15.03.2021 г.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies