

Role of urinary tract microbiota and urine proteome in urolithiasis pathogenesis
https://doi.org/10.36485/1561-6274-2024-28-2-85-93
EDN: PRGIJT
Abstract
The pathogenetic approach to the metaphylaxis of urolithiasis is universally a socially significant health problem due to the increase in morbidity and, especially, its recurrent course, despite the achievements of pharmacotherapy and the use of lithotripsy. Pathological crystallogenesis is considered as a consequence of exceeding the solubility threshold of a number of mineral components of urine, on the one hand, and as a consequence of posttranslational defects of the main proteome of urination - uromodulin (UMOD), demonstrating in healthy people a sanogenetic system for ensuring the stability of biophysical homeostasis: colloidal properties of urine. However, in addition, UMOD, by binding mannose-dependent pills of infectious agents, blocks the contact of bacteria with urotheliocytes, despite the fact that infection of the urinary tract is a known factor of urolithiasis. By modeling the urine of healthy individuals by coincubation with E. coli bacteria, a decrease in the concentration of polymerized uromodulin in urine was demonstrated as a factor in increasing the risk of formation of calcium oxalate crystals
Keywords
About the Authors
N. A. VerlovRussian Federation
Nikolay A. Verlov, Ph.D., Head of Resource Center of the Molecular and Radiation Biophysics Division
188300, Leningradskaya oblast, Gatchina 1, mkr. Orlova roshcha
V. S. Burdakov
Russian Federation
Vladimir S. Burdakov, staffscientist of the Molecular and Radiation Biophysics Division
188300, Leningradskaya oblast, Gatchina 1, mkr. Orlova roshcha
L. A. Ivanova
Russian Federation
Lyubov A. Ivanova, staffscientist of the Molecular and Radiation Biophysics Division
188300, Leningradskaya oblast, Gatchina 1, mkr. Orlova roshcha
I. A. Kulakov
Russian Federation
Ignatiy A. Kulakov, laboratory assistant of the Molecular and Radiation Biophysics Division
188300, Leningradskaya oblast, Gatchina 1, mkr. Orlova roshcha
A. A. Bogdanov
Russian Federation
Aleksey A. Bogdanov
197758, Saint-Petersburg
V. L. Emanuel
Russian Federation
Prof. Vladimir L. Emanuel, MD, PhD, DMedSci, head
197022, Saint-Petersburg
References
1. Pak CY. Kidney stones. Lancet 1998;351(9118):1797–1801. doi:10.1016/S0140-6736(98)01295-1
2. Coe FL, Parks JH, Asplin JR. The pathogenesis and treatment of kidney stones. N Engl J Med 1992;327(16):1141–1152. doi:10.1056/NEJM199210153271607
3. Curhan GC, Willett WC, Speizer FE, Stampfer MJ. Twentyfour-hour urine chemistries and the risk of kidney stones among women and men. Kidney Int 2001;59(6):2290–2298. doi:10.1046/j.1523-1755.2001.00746.x
4. Borghi L, Guerra A, Meschi T et al. Relationship between supersaturation and calcium oxalate crystallization in normals and idiopathic calcium oxalate stone formers. Kidney Int 1999;55(3):1041–1050. doi:10.1046/j.1523-1755.1999.0550031041.x
5. Borghi L, Meschi T, Amato F, Briganti A, Novarini A, Giannini A. Urinary volume, water and recurrences in idiopathic calcium nephrolithiasis: a 5-year randomized prospective study. J Urol 1996;155(3):839–843
6. Flannigan R, Choy WH, Chew B, Lange D. Renal struvite stones-pathogenesis, microbiology, and management strategies. Nat Rev Urol 2014;11(6):333–341. doi:10.1038/nrurol.2014.99
7. Pak CY, Poindexter JR, Adams-Huet B, Pearle MS. Predictive value of kidney stone composition in the detection of metabolic abnormalities. Am J Med 2003;115(1):26–32. doi:10.1016/s0002-9343(03)00201-8
8. Thompson RB, Stamey TA. Bacteriology of infected stones. Urology 1973;2(6):627–633. doi:10.1016/0090-4295(73)90323-3
9. Tavichakorntrakool R, Prasongwattana V, Sungkeeree S, et al. Extensive characterizations of bacteria isolated from catheterized urine and stone matrices in patients with nephrolithiasis. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc – Eur Ren Assoc 2012;27(11):4125–4130. doi:10.1093/ndt/gfs057
10. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248–254. doi: 10.1006/abio.1976.9999
11. Kobayashi K, Fukuoka S. Conditions for solubilization of Tamm-Horsfall protein/uromodulin in human urine and establishment of a sensitive and accurate enzyme-linked immunosorbent assay (ELISA) method. Arch Biochem Biophys 2001;388(1):113–120. doi:10.1006/abbi.2000.2265
12. Chevallet M, Luche S, Rabilloud T. Silver staining of proteins in polyacrylamide gels. Nat Protoc 2006;1(4):1852–1858. doi:10.1038/nprot.2006.288
13. Porowski T, Zoch-Zwierz W, Wasilewska A, Spotyk A, Konstantynowicz J. Normative data on the Bonn Risk Index for calcium oxalate crystallization in healthy children. Pediatr Nephrol Berl Ger 2007;22(4):514–520. doi:10.1007/s00467-006-0383-0
14. Laube N, Schneider A, Hesse A. A new approach to calculate the risk of calcium oxalate crystallization from unprepared native urine. Urol Res 2000;28(4):274–280. doi:10.1007/s002400000124
15. Schaeffer C, Santambrogio S, Perucca S, Casari G, Rampoldi L. Analysis of uromodulin polymerization provides new insights into the mechanisms regulating ZP domain-mediated protein assembly. Mol Biol Cell 2009;20(2):589–599. doi:10.1091/mbc.e08-08-0876
Review
For citations:
Verlov N.A., Burdakov V.S., Ivanova L.A., Kulakov I.A., Bogdanov A.A., Emanuel V.L. Role of urinary tract microbiota and urine proteome in urolithiasis pathogenesis. Nephrology (Saint-Petersburg). 2024;28(2):85-93. (In Russ.) https://doi.org/10.36485/1561-6274-2024-28-2-85-93. EDN: PRGIJT