Homocysteine in chronic kidney disease: Clinical diagnostic aspects
I. T. Murkamilov,
K. A. Aitbaev,
V. V. Fomin,
Zh. A. Murkamilova,
I. O. Kudaibergenova,
F. A. Yusupov,
Z. А. Aidarov https://doi.org/10.33667/2078-5631-2023-4-23-29
Abstract
Chronic kidney disease (CKD) is one of the most common pathologies worldwide. With CKD, cardiovascular risk increases and mortality rises. The article presents the role of homocysteine as a laboratory marker of renal failure and the development of cardiovascular disease. Homocysteine is a thiol-containing amino acid, which is an intermediate product of methionine metabolism, which is metabolized in two ways: due to the transfer of the sulfate group, which occurs in the presence of vitamin B 6, or remethylation, which occurs in the presence of vitamin B 12 and folic acid. Normally, in an adult, the concentration of total homocysteine in blood plasma does not exceed 15 μmol/L. It has been shown that with CKD, hyperhomocysteinemia is observed at the initial stages and its frequency increases at the pre- and dialysis stages of the disease. Hyperhomocysteinemia provokes endothelial dysfunction, accelerates systemic atherosclerosis, increases the risk of atherothrombotic complications. Evaluation of plasma homocysteine levels may be useful in stratifying nephrocardio- and cerebrovascular risk in CKD.
About the Authors
I. T. Murkamilov
Kyrgyz State Medical Academy n. a. I. K. Akhunbaev; Kyrgyz-Russian Slavic University
Kyrgyzstan
Kyrgyzstan
Murkamilov Ilkhom T., DM Sci (habil.), chairman of the board of the Society of Specialists in Chronic Kidney Disease of Kyrgyzstan, associate professor at Dept of Faculty Therapy; associate professor at Dept of Therapy No. 2
Bishkek
K. A. Aitbaev
Scientific Research Institute of Molecular Biology and Medicine
Kyrgyzstan
Kyrgyzstan
Aitbaev Kubanych A., DM Sci (habil.), professor, member of the board of the Society of Specialists in Chronic Kidney Disease of Kyrgyzstan, head of Laboratory of Pathological Physiology
Bishkek
V. V. Fomin
First Moscow State Medical University n. a. I. M. Sechenov
Russian Federation
Russian Federation
Fomin Viktor V., DM Sci (habil.), professor, corresponding member of RAS, head of Dept of Faculty Therapy No. 1 of the Institute of Clinical Medicine n. a.
N. V. Sklifosovsky, vice-rector for Innovation and Clinical Activities
Moscow
Zh. A. Murkamilova
Kyrgyz-Russian Slavic University
Kyrgyzstan
Kyrgyzstan
Murkamilova Zhamila A., post-graduate student of Dept of Therapy No. 2 specializing in General Medicine
Bishkek
I. O. Kudaibergenova
Kyrgyz State Medical Academy n. a. I. K. Akhunbaev
Kyrgyzstan
Kyrgyzstan
Kudaibergenova Indira O., DM Sci (habil.), professor, rector
Bishkek
F. A. Yusupov
Osh State University
Kyrgyzstan
Kyrgyzstan
Yusupov Furkat A., DM Sci (habil.), professor, chief neurologist of the Southern Region of Kyrgyzstan, member of the board of the Society of Specialists in Chronic Kidney Disease of Kyrgyzstan, head of Dept of Neurology, Neurosurgery and Psychiatry of Faculty of Medicine
Osh
Z. А. Aidarov
Kyrgyz State Medical Academy n. a. I. K. Akhunbaev
Kyrgyzstan
Kyrgyzstan
Aidarov Ziyabidin A., DM Sci (habil.), professor, member of the board of the Society of Specialists in Chronic Kidney Disease of Kyrgyzstan, head of Dept of Public Health and Healthcare, dean of Faculty of Medicine
Bishkek
References
1. Centers for Disease Control and Prevention. Chronic Kidney Disease in the United States, 2019. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2019.
2. Moiseev VC, Mukhin NA. Cardiovascular risk and chronic kidney disease: cardio- and nephroprotection strategies. Clinical Nephrology. 2014; 2: 4–29 (In Russ).
3. Kamyshnikova LA, Yefremova OA, Pivovar RS. Features of cardiorenal relationships at patients with the chronic disease of kidney. The current state of the problem. Scientific Statements. Series Medicine. Pharmacy. 2017; 5(254): 13–21. (In Russ).
4. Skvortsov YuI, Korolkova AS. Homocysteine as a risk factor of ischemic heart disease development (review). Saratov Journal of Medical Scientific Research. 2011; 7: 3: 619–624. (In Russ).
5. Protopopov AA, Nesterenko OV, Borodulin VB, Shevchenko OV. Hyperhpmocysteinemia as a predictor of chronic pyelonephritis progression. Clinical Nephrology. 2013; 6: 33–36. (In Russ).
6. Chmurzynska A, Seremak-Mrozikiewicz A, Malinowska AM, et al. Associations between folate and choline intake, homocysteine metabolism, and genetic polymorphism of MTHFR, BHMT and PEMT in healthy pregnant Polish women. Nutrition & Dietetics.2020; 77: 3: 368–372. https://doi.org/10.1111/1747–0080.12549
7. Medvedev D.V., Zvyagina V.I. Molecular mechanisms of homocysteine’s toxic action. Cardiological Bulletin. 2017; 1: 52–57. (In Russ).
8. Smirnov AV, Dobronravov VA, Golubev RV, et al. Incidence of hyperhomocycteinemia depending on the stage of chronic renal disease. Nephrology (Saint-Petersburg). 2005; 9 (2): 48–52. https://doi.org/10.24884/1561–6274–2005–9–2–48–52 (In Russ).
9. Khrulev АЕ, Grigoryeva VN, Emelyanova МА, Khrulev SЕ. Primary hyperhomocystenemia as a risk factor of associated development of cerebrovascular, renal and oncological pathology. Neurological Bulletin.2017; 2: 91–94. (In Russ).
10. Ryabov VV, Gomboeva SB, Lugacheva YD, et al. Unfavorable variants of folate metabolism genes in patients with acute coronary syndrome in non-obstructive coronary atherosclerosis. Russian Journal of Cardiology. 2018; (10): 33–42. https://doi.org/10.15829/1560–4071–2018–10–33–42 (In Russ).
11. Tulceva S.N. The significance of hyperhomocysteinemia in the pathogenesis of the ischemic thrombosis of retinal veins. 2008; 3: 1: 31–39. (In Russ).
12. Zhloba AA, Subbotina TF. The evaluation of folate status using total homocysteine in hypertensive patients. Medical Journal of the Russian Federation. 2019; 25: 3: 158–165. https://doi.org/10.18821/0869–2106–2019–25–3–158–165 (In Russ).
13. Kruglova MP, Ivanov AV, Vvedenskaya OYu, Kubatiev AA. Hyperhomocysteinemia and chronic kidney disease. Pathological physiology and experimental therapy. 2018; 4: 195–201. (In Russ).
14. Bostom AG, Culleton BF. Hyperhomocysteinemia in chronic renal disease. J Am Soc Nephrol. 1999; 10: 4: 891–900.
15. Cohen E, Margalit I, Shochat T, et al. The relationship between the concentration of plasma homocysteine and chronic kidney disease: a cross sectional study of a large cohort. Journal of Nephrology. 2019; 32: 5: 783–789. https://doi.org/10.1007/s40620–019–00618-x
16. Bhawane A, Jat SL, Kalra OP, et al. Correlation of serum homocysteine levels with carotid atherosclerosis in patients with chronic kidney disease. Paripex-Indian Journal of Research.2019; 8: 11. https://doi.org/10.36106/paripex
17. Aren SK, Bhardwaj V. Association between chronic kidney disease and plasma homocysteine level-a hospital-based study. International Journal of Medical and Biomedical Studies. 2019; 3: 8: 37–139. https://doi.org/10.32553/ijmbs.v3i8.472
18. Zhang YM, Zhou XJ, Shi SF, et al. Homocysteine and IgA nephropathy: observational and Mendelian randomization analyses. Chinese Medical Journal. 2020; 133 (3): 277–284. https://doi.org/10.1097/CM9.0000000000000613
19. Ma N, Xu N, Yin D, et al. Relationship between plasma total homocysteine and the severity of renal function in Chinese patients with type 2 diabetes mellitus aged ≥ 75 years. Medicine. 2020; 99: 27. С. e20737. https://doi.org/10.1097/MD.0000000000020737
20. Huang YC, Huang SC, Chung PS, Chen CH. Plasma Homocysteine and Glutathione Are Independently Associated with Estimated Glomerular Filtration Rates in Patients with Renal Transplants. Transplantation proceedings. Elsevier. 2019; 51: 8: 2667–2670. https://doi.org/10.1016/j.transproceed.2019.02.053
21. Ilyicheva OI, Kharlamova UV, Nezdoymina NN, Scherbakov AV. Hyperhomocysteinemia in patients with chronic kidney disease. Bulletin of SUSU. 2010; 24: 75–79. (In Russ).
22. Welch GN, Loscalzo J. Homocysteine and atherothrombosis.New England journal of medicine.1998; 338: 15: 1042–1050. https://doi.org/10.1056/NEJM199804093381507
23. Refsum H, Ueland PM, Nygård O, Vollset SE. Homocysteine and cardiovascular disease. Annual Review of Medicine. 1998; 49; 1: 31–62. https://doi.org/10.1146/annurev.med.49.1.31
24. Makris M. Hyperhomocysteinemia and thrombosis. Clinical & Laboratory Haematology. 2000; 22: 3: 133–143. https://doi.org/10.1046/j.1365–2257.2000.00301.x
25. Balint B, Jepchumba VK, Guéant JL, Guéant-Rodriguez RM. Mechanisms of homocysteine-induced damage to the endothelial, medial and adventitial layers of the arterial wall. Biochimie. 2020; 173: 100–106. https://doi.org/10.1016/j.biochi.2020.02.012
26. Karger AB, Steffen BT, Nomura SO, et al. Association between homocysteine and vascular calcification incidence, prevalence, and progression in the MESA cohort. Journal of the American Heart Association. 2020; 9: 3. С. e013934. https://doi.org/10.1161/JAHA.119.013934
27. Xubutiya MSh, Shevchenko OP. Homocysteine in coronary heart disease and heart transplant. M.: Refarm, 2004. 272 s. (In Russ).
28. Lusov VA, Lebedeva AYu, Mikhailova KV. Hyperhomocysteinemia, intravascular hemostasis disturbances, and clinical course of myocardial infarction. Russian Journal of Cardiology. 2007; (2): 41–46. https://doi.org/10.15829/1560–4071–2007–2–41–46 (In Russ)
29. Ragino YI, Chernyavsky AM, Tikhonov AV, et al. Blood lipid and non-lipid biomarkers in Novosibirsk men with coronary atherosclerosis. Russian journal of cardiology. 2009; (2): 31–35. https://doi.org/10.15829/1560–4071–2009–2–31–35 (In Russ).
30. Amen SO, Baban ST. Association of Hyperhomocysteinemia with Acute Myocardial Infarction in Iraqi Patients. Eur Cardiol. 2020; 15: e28. Published 2020 May 15. https://doi.org/10.15420/ecr.2020.15.1.PO5
31. Si J, Li XW, Wang Y, et al. Relationship between serum homocysteine levels and long-term outcomes in patients with ST-segment elevation myocardial infarction. Chinese Medical Journal. 2019; 132 (9): 1028–1036. https://doi.org/10.1097/CM9.0000000000000159
32. Park S, Park GM, Ha J, et al. Homocysteine is not a risk factor for subclinical coronary atherosclerosis in asymptomatic individuals. Plos one. 2020; 15: 4: e0231428. https://doi.org/10.1371/journal.pone.0231428
33. Belaya OL, Bondar KYu, Markova LI, et al. Gender-specific differences of homocysteinemia and its influence on oxidative stress parameters and endothelial function in patients with stable forms of coronary heart disease. Clinical Medicine. 2017; 8: 705–712. https://doi.org/10.18821/0023–2149–2017–95–8–705–712 (In Russ).
34. D’Angelo A, Selhub J. Homocysteine and thrombotic disease. Blood. The Journal of the American Society of Hematology. 1997; 90: 1: 1–11.
35. Podzolkov VI, Bragina AE, Bragina NA. Prognostic significance of endothelial dysfunction markers in arterial hypertension. Russian Journal of Cardiology. 2018; (4): 7–13. https://doi.org/10.15829/1560–4071–2018–4–7–13 (In Russ).
36. Klinkova AS, Kamenskaya OV. Microcirculatory reserves and tissue metabolism reactivity in various stage ischemic congestive heart failure. Russian Journal of Cardiology. 2016; (8): 42–47. https://doi.org/10.15829/1560–4071–2016–8–38–42 (In Russ).
37. Kharlamova UV, Ilyicheva OE, Nezdojmina NN, Scherbakov AV. Homocysteine – the Non-Conventional Risk Factor for Thrombotic Complications in Patients Treating by Hemodialysis. Journal of General Medicine. 2011; 1: 61–64. (In Russ).
38. Lazarenko VA, Bobrovskaya EA, Sorokin AV. Hyperhomocysteinemia: peripheral atherosclerosis and reconstructive surgery. Kursk Scientific and Practical Bulletin ‘Man and his health’. 2014; 4:63–66. (In Russ).
39. McCully KS. Homocysteine and the pathogenesis of atherosclerosis. Expert review of clinical pharmacology.2015; 8: 2: 211–219. https://doi.org/10.1586/17512433.2015.1010516
40. Reshetnyak TM, Seredavkina NV, Nasonov EL. Is hyperhomocysteinemia a risk factor of thrombosis in antiphospholipid syndrome? Thrombosis, Hemostasis and Rheology. 2019; 2: 37–44. https://doi.org/10.25555/THR.2019.2.0878. (In Russ).
41. Sibireva OF, Zhavoronok TV, Kaljuzhina EV, Kaluzhin VV. Hereditary risk factors for intravascular coagulation and homocysteine levels in patients with chronic alcoholism. Narcology.2019; 3: 52–58. https://doi.org/10.25557/1682–8313.2019.03.52–58
42. Sherbak SG, Sarana AM, Makarenko SV, Kamiliva TA. Maximov AG. Some genetical peculiarities of metabolism of homocysteine, folate, and nitric oxide as risk factors of ischemic heart disease. Herald of the Northwestern State Medical University named after I.I. Mechnikov. Herald of North-Western State Medical University named after I.I. Mechnikov. 2016; 1: 123–130. (In Russ)
43. Modern understanding of the clinical importance of hyperhomocysteinemia: emphasis on diabetes mellitus. Attending Doctor Journal. 2017; 9: 58–65. (In Russ).
44. Murphy D, Drawz PE. Blood Pressure Variability in CKD: Treatable or Hypertension’s Homocysteine? 2019; 14 (2) 175–177. https://doi.org/10.2215/CJN.14991218
45. Azzini E, Ruggeri S, Polito A. Homocysteine: Its possible emerging role in at-risk population groups. International Journal of Molecular Sciences. 2020; 21: 4: 1421. https://doi.org/10.3390/ijms21041421
46.
Review
For citations:
Murkamilov I.T., Aitbaev K.A., Fomin V.V., Murkamilova Zh.A., Kudaibergenova I.O., Yusupov F.A., Aidarov Z.А. Homocysteine in chronic kidney disease: Clinical diagnostic aspects. Medical alphabet. 2023;(4):23-29. (In Russ.) https://doi.org/10.33667/2078-5631-2023-4-23-29
Views:
1019
Email this article 