Generate QR code
Open Access
Subscription Access
KLOTHO PROTEIN IN CLINICAL PRACTICE
https://doi.org/10.17021/2021.16.2.26.36
Abstract
An analysis of the longevity gene klotho, discovered in 1997 by the Japanese scientist M. Kuro- o, is presented. From that moment to the present day, the protein under study has been investigated in experimental models in animals and humans in clinical practice, including in normand pathology. The questions of the pathogenetic influence of klotho on the development of chronic kidney disease, some cardiovascular diseases and diabetes mellitus (often interrelated) - the main causes of the non-infectious pandemic of the XXI century are considered. The undoubted role of different concentrations of this protein in the progression of these diseases has been proven. The possibilities of modern laboratory diagnostics for the determination of klotho in blood and urine, available in practical health care, are indicated. The impact of some drugs that have a positive effect on increasing the concentration of the protein under study in the blood is described.
About the Authors
L. V. Zaklyakova
Astrakhan State Medical University
Russian Federation
Russian Federation
E. G. Ovsyannikova
Astrakhan State Medical University
Russian Federation
Russian Federation
B. N. Levitan
Astrakhan State Medical University
Russian Federation
Russian Federation
B. A. Shamgunova
Astrakhan State Medical University
Russian Federation
Russian Federation
I. Yu. Petelina
Astrakhan State Medical University
Russian Federation
Russian Federation
M. Yu. Bolgova
Astrakhan State Medical University
Russian Federation
Russian Federation
M. A. Voznyuk
Astrakhan State Medical University
Russian Federation
Russian Federation
References
1. Веремеенко, Д. Е. α-Klotho - маркер риска фиброза и кальцификации, когнитивных нарушений и смертности, регулируемый аэробными тренировками. Справочный портал nestarenie RU / Д. Е. Веремеенко. - Режим доступа: https://nestarenie.ru/klotho.html, дата обращения: 20.04.2021.
2. Волгина, Г. В. Национальные рекомендации по минеральным и костным нарушениям при хронической болезни почек (Российское диализное общество) / Г. В. Волгина, В. А. Добронравов, Л. Я. Рожинская, А. В. Смирнов, Н. А. Томилина, Г. Д. Шостка, В. А. Анашкин, А. М. Андрусев, Р. П. Герасимчук, А. Ю. Земченков, Г. А. Дюбанова, А. Г. Строков, В. Ю. Шило // Нефрология и диализ. - 2011. - Т. 13, № 1. - С. 33-51.
3. Волков, М. Биохимические показатели фосфорно-кальциевого обмена у пациентов с хронической болезнью почек 1-5 стадий / М. Волков // Нефрология. - 2009. - Т. 13, № 3. - С. 49-51.
4. Колбин, А. С. Анализ медицинской технологии коррекции гиперфосфатемии при хронической болезни почек / А. С. Колбин, А. А. Курылев, О. Н. Котенко, Г. В. Волгина // Качественная клиническая практика. - 2013. - № 3. - С. 2-12.
5. Милованова, Л. Ю. Значение морфогенетических белков FGF-23 и Klotho как предикторов прогноза хронической болезни почек / Л. Ю. Милованова, Ю. С. Милованов, Л. В. Козловская, Н. А. Мухин / Терапевтический архив. - 2014. - № 4. - С. 36-44.
6. Плотникова, А. А. Клиническое значение определения сывороточной концентрации морфогенетических белков FGF-23 и Klotho у больных хронической почечной недостаточностью : дис. … канд. мед. наук / А. А. Плотникова. - Челябинск, 2018. - 128 с.
7. Сорокина, Ю. А. Влияние лекарственных средств на уровень белка Клото / Ю. А. Сорокина, А. А. Мосина, А. Д. Постникова, Л. В. Ловцова, Е. В. Макарова, О. В. Занозина // Международный научно-исследовательский журнал. - 2020. - № 12-2 (102). - С. 142-145. doi: 10.23670/IRJ.2020.102.12.061.
8. Ark, J. Circulating alpha - klotho levels are not disturbed in patients with type 2 diabetes with and without macrovascular disease in the absence of nephropathy / J. Ark, H. P. Hammes, M. Dijk, C. Lexis, I. Horst, C. Zeebregts, M. Vervloet, B. Wolffenbuttel, H. Goor, J. Hillebrands // Cardiovasc Diabetol. - 2013. - № 12. - Р. 116. doi: 10.1186/1475-2840-12-116.
9. Brandenburg, V. Relationship between sclerostin and cardiovascular calcification in hemodialysis patients : a cross-sectional study / V. M. Brandenburg, R. Kramann, R. Koos, T. Krüger, L. Schurgers, G. Mühlenbruch, S. Hübner, U. Gladziwa, C. Drechsler, M. Ketteler // BMC Nephrol. - 2013. - № 14. - Article number: 219. doi: 10.1186/1471-2369-14-219.
10. Buchanan, S. Klotho, Aging, and the Failing Kidney / S. Buchanan, E. Combet, P. Stenvinkel, P. G. Shiels // Front Endocrinol (Lausanne). - 2020. - Vol. 11. - 560. doi: 10.3389/fendo.2020.00560.
11. Chacar, F. C. Vitamin D Metabolism and Its Role in Mineral and Bone Disorders in Chronic Kidney Disease in Humans, Dogs and Cats / F. C. Chacar, M. M. Kogika, R. V. A. Zafalon, M. A. Brunetto // Metabolites. - 2020. - Vol. 10, № 12. - 499. doi: 10.3390/metabo10120499.
12. Cheikhi, A. Klotho : An Elephant in Aging Research / A. Cheikhi, A. Barchowsky, A. Sahu, S. N. Shinde, A. Pius, Z. J. Clemens, H. Li, C. A. Kennedy, J. D. Hoeck, M. Franti, F. Ambrosio // J. Gerontol. A Biol. Sci. Med. Sci. - 2019. - Vol. 74, № 7. - Р. 1031-1042. doi: 10.1093 /gerona / glz061.
13. Chung, C. α-Klotho expression determines nitric oxide synthesis in response to FGF-23 in human aortic endothelial cells / C. P. Chung, Y. C. Chang, Y. Ding, K Lim, Q. Liu, L. Zhu, W. Zhang, T. S. Lu, G. Molostvov, D. Zehnder, L. L. Hsiao // PLoS One. - 2017. - Vol. 12, № 5. - e0176817. doi:10.1371 / journal. pone.0176817.
14. Couser, W. G. The contribution of chronic kidney disease to the global burden of major noncommunicable diseases / W. G. Couser, G. Remuzzi, S. Mendis, M. Tonelli // Kidney Int. - 2011. - № 12. - Р. 1258-1270. doi: 10.1038 / ki.2011.368.
15. Cozzolino, M. Vascular calcification and uremia : what do we know? / M. Cozzolino, S. Mazzaferro, F. Pugliese, D. Brancaccio // Am. J. Nephrol. - 2008. - Vol. 28, № 2. - P. 339-346.
16. Dongming, F. Serum klotho protein levels and their correlations with the progression of type 2 diabetes mellitus / F. Dongming, W. Hongfei, D. Xianggui, Y. Yang, X. Pang, Y. Xu // J. Diabetes Complications. - 2017. - Vol. 31, № 3. - Р. 594-598.
17. Forster, R. E. Vitamin D receptor controls expression of the anti - aging klotho gene in mouse and human renal cells / R. E. Forster, P. W. Jurutka, J. C. Hsieh // Biochem. Biophys. Res. Commun. - 2011. - Vol. 414, № 3. - Р. 557-562. doi: 10.1016 / j.bbrc.2011.09.117.
18. Höck, A. D. A Review on the Potential Role of Vitamin D and Mineral Metabolism on Chronic Fatigue Illnesses / A. D. Höck // J. Clin. Nephrol. Ren. Care. - 2016. - Vol. 2. - Р. 8-13.
19. Hu, M. C. Klotho : a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule / M. C. Hu, M. Shi, J. Zhang, J. Pastor, T. Nakatani, B. Lanske, M. S. Razzaque, K. P. Rosenblatt, M. G. Baum, M. Kuro-o, O. W. Moe // FASEB J. - 2010. - Vol. 24, № 9. - Р. 3438-3450. doi: 10.1096 / fj.10-154765.
20. Hu, M. C. Klotho deficiency causes vascular calcification in chronic kidney disease / M. C. Hu, M. Shi, J. Zhang, H. Quiñones, C. Griffith, M. Kuro-o, O. W. Moe // J. Am. Soc. Nephrol. - 2011. - Vol. 22, № 1. - P. 124-136.
21. Internacional Diabetes Federation. IDF Diabetes Atlas, 9th Еdition. Brussels, Belgium : 2019. - Режим доступа: https://diabetesatlas.org/data/en/, свободный. - Заглавие с экрана. - Яз. англ. - Дата обращения : 20.04.2021.
22. Karalliedde, J. Effect of rennin-angiotensin system blockade on soluble Klotho in patients with type 2 diabetes, systolic hypertension, and albuminuria / J. Karalliedde, G. Maltese, B. Hill, G. Viberti, L. Gnudi // Clin. J. Am. Soc. Nephrol. - 2013. - Vol. 8, № 11. - Р. 1899-1905. doi: 10.2215/CJN.02700313.
23. Koh, N. Severely reduced production of klotho in human chronic renal failure kidney / N. Koh, T. Fujimori, S. Nishiguchi, A. Tamori, S. Shiomi, T. Nakatani // Biochemical and biophysical research communications. - 2001. - Vol. 280, № 4. - Р. 2538-2550.
24. Kuro-o, M. Mutation of the mouse klotho gene leads to a syndrome resembling ageing / M. Kuro-o, Y. Matsumura, H. Aizawa, H. Kawaguchi, T. Suga, T. Utsugi, Y. Ohyama, M. Kurabyashi // Nature. - 1997. - Vol. 390, № 6655. - P. 45-51. doi: 10.1038/36285.
25. Kuro-o, M. Klotho in chronic kidney disease - What`s new? / M. Kuro-o // Nephrol. Dial. Transplant. - 2009. - Vol. 24, № 6. - Р. 1705-1708. doi: 10.1093/ndt/gfp069.
26. Kuro-o, M. Klotho and β Klotho / M.Kuro-o // Adv. Exp. Med. Biol. - 2012. - Vol. 728. - P. 25-40. doi: 10.1007/978-1-4614-0887-1_2.
27. Kuro-o, M. FGF23 - α Klotho as a paradigm for a kidney-bone network / M. Kuro-o, O. W. Moe // Bone. - 2017. - Vol. 100. - Р. 4-18. doi: 10.1016 / j.bone.2016.11.013.
28. Kuro-o, M. The Klotho proteins in health and disease / M. Kuro-o // Nat. Rev. Nephrol. - 2019. - Vol. 15, № 1. - Р. 27-44. doi: 10.1038 / s41581-018-0078-3.
29. Lacroix, J. S. Potential application of fibroblast growth factor 23 - klotho axis in chronic kidney disease / J. S. Lacroix, P. Urena-Torres // Nephrol. Ther. - 2020. - Vol. 16, № 2. - Р. 83-92. doi: 10.1016/j.nephro.2019.05.003.
30. Lanske, B. Molecular interactions of FGF23 and PTH in phosphate regulation / B. Lanske, M. S. Razzaque // Kidney Int. - 2014. - Vol. 86, № 6. - Р. 1072-1074. doi: 10.1038 / ki.2014.316.
31. Lee, S. Vascular Calcification - New Insights Into Its Mechanism / S. Lee, I. Lee, J. Jeon // Int. J. Mol. Sci. - 2020. - Vol. 21, № 8. - Р. 2685. doi: 10.3390 / ijms21082685.
32. Levey, A. S. Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from Kidney Disease Improving Global Outcomes / A. S. Levey, R. Atkins, J. Coresh // Kidney Int. - 2007. - Vol. 72. - Р. 247-259. doi: 10.1038 / sj.ki.5002343.
33. Li, S. A. Immunohistochemical localization of Klotho protein in brain, kidney, and reproductive organs of mice / S. A. Li, M. Watanabe, H. Yamada, A. Nagai, M. Kinuta, K. Takei // Cell structure and function. - 2004. - Vol. 29, №. 4. - Р. 91-99. doi: 10.1247/csf.29.91.
34. Lim, S. C. Elevated circulating alpha-klotho by angiotensin II receptor blocker losartan is associated with reduction of albuminuria in type 2 diabetic patients / S. C. Lim // J. Renin Angiotensin Aldosterone Syst. - 2014. - Vol. 15, № 4. - P. 487-490. doi: 10.1177/1470320313475905.
35. Liu, Z. Metformin inhibits 17β - estradiol - induced epithelial - to - mesenchymal transition via β Klotho - related ERK 1/2 signaling and AMPK α signaling in endometrial adenocarcinoma cells // Z. Liu, S. Qi, X. Zhao, M. Li, S. Ding, J. Lu, H. Zhang // Oncotarget. - 2016. - Vol. 7, № 16. - P. 21315-21331. doi: org/10.18632/oncotarget.7040.
36. Martin, A. Regulation and function of the FGF23 Klotho endocrine pathways / A. Martin, V. David // Physiol. Rev. - 2012. - Vol. 92, № 1. - P. 131-155.
37. Olejnik, А. The Biological Role of Klotho Protein in the Development of Cardiovascular Diseases / A. Olejnik, A. Franczak, A. Krzywonos-Zawadzka, M. Kałużna-Oleksy, I. Bil-Lula // Nephrol. Dial. Transplant. - 2018. - Vol. 2018. - 5171945. doi: 10.1155/2018/5171945.
38. Ramon, I. Fibroblast growth factor 23 and its role in phosphate homeostasis / I. Ramon, P. Kleynen, J. J. Body, R. Karmali // Eur. J. Endocrinol. - 2010. - Vol. 162, № 1. - P. l-10.
39. Saar-Kovrov, V. Shedding of Klotho : Functional Implications in Chronic Kidney Disease and Associated Vascular Disease / V. Saar-Kovrov, M. M. P. C. Donners, E. P. C. van der Vorst // Front. Cardiovasc. Med. - 2021. - 617842. doi: 10.3389/fcvm.2020.617842.
40. Shao, J. S. Msx2 promotes cardiovascular calcification by activating paracrine Wnt signals / J. S. Shao, S. L. Cheng, J. M. Pingsterhaus, N. Charlton-Kachigian, A. P. Loewy, D. A. Towler // J. Clin. Invest. - 2005. - Vol. 115, № 5. - Р. 1210-1220.
41. Shimamura,Y. Serum levels of soluble secreted α Klotho are decreased in the early stages of chronic kidney disease, making it a probable novel biomarker for early diagnosis/ Y. Shimamura, K. Hamada, K. Inoue // Clin. Exp. Nephrol. - 2012. - Vol. 16, №5. - Р. 722-729. doi: 10.1007/s10157-012-0621-7.
42. Wolf, M. Update on fibroblast growth factor 23 in chronic kidney disease / M. Wolf // Kidney Int. - 2012. - Vol. 82, № 7. - Р. 737-747. doi: 10.1038/ki.2012.176.
43. Yoshikawa, R. The age-related changes of dietary phosphate responsiveness in plasma 1,25-dihydroxyvitamin D levels and renal Cyp 27 b1 and Cyp 24 a1 gene expression is associated with renal α-Klotho gene expression in mice / R. Yoshikawa, H. Yamamoto, O. Nakahashi, T. Kagawa, M. Tajiri, M. Nakao, S. Fukuda, H. Arai, M. Masuda, M. Iwano, E. Takeda, Y. Taketani // J. Clin. Biochem. Nutr. - 2018. - Vol. 62, № 1. - Р. 68-74. doi: 10.3164/jcbn.17-20.
44. Zhang, L. Clinical implication of alterations in serum Klotho levels in patients with type 2 diabetes mellitus and its associated complications / L. Zhang, T. Liu // J. Diabetes Complications. - 2018. - Vol. 32, № 10. - P. 922-930. doi: 10.1016 / j.jdiacomp.2018.06.002.
45. Zheng, Z. A systematic review and meta-analysis of telmisartan versus valsartan in the management of essential hypertension / Z. Zheng, S. Lin, H. Shi // J. Clin. Hypertens (Greenwich). - 2010. - Vol. 12, № 6. - Р. 414-421. doi: 10.1111 / j.1751-7176.2010.00287.x.
46. Zou, D. The role of klotho in chronic kidney disease / D. Zou, W. Wu, Y. He, S. Ma, J. Gao //BMC Nephrol. - 2018. - Vol. 19, № 1. - Article number: 285. doi: 10.1186/s12882-018-1094-z.
Review
For citations:
Zaklyakova L.V., Ovsyannikova E.G., Levitan B.N., Shamgunova B.A., Petelina I.Yu., Bolgova M.Yu., Voznyuk M.A. KLOTHO PROTEIN IN CLINICAL PRACTICE. Astrakhan medical journal. 2021;16(2):26-36. (In Russ.) https://doi.org/10.17021/2021.16.2.26.36
Views:
308
Email this article 