Hyperhomocysteinemia in patients with chronic kidney disease and its relationship with the functional status of the cardiovascular system

  • K. P. Postovitenko National Pirogov Memorial Medical University, Vinnytsia
  • I. A. Iliuk National Pirogov Memorial Medical University, Vinnytsia
  • S. V. Shevchuk National Pirogov Memorial Medical University, Vinnytsia
  • G. V. Bezsmertna Scientific and Research Institute of Invalid Rehabilitation (Educational Scientific Treatment Complex) of National Pirogov Memorial Medical University
  • І. O. Bezsmertnyi Scientific and Research Institute of Invalid Rehabilitation (Educational Scientific Treatment Complex) of National Pirogov Memorial Medical University
  • I. V. Kurylenko Scientific and Research Institute of Invalid Rehabilitation (Educational Scientific Treatment Complex) of National Pirogov Memorial Medical University
Keywords: homocysteine, renal failure, left ventricular hypertrophy, myocardial contractile function, endothelial dysfunction


Chronic kidney disease (CKD) is an important medical, social and economic problem nowadays. Patients with CKD are known to have an increased risk of development and progression of cardiovascular diseases. However, the causes and pathogenesis of cardiovascular complications are not well understood. One of the recently recognized “non-traditional” risk factors for the increased development of cardiovascular pathology in severe stages of CKD is hyperhomocysteinemia (HHC). The article presents the results of study of HHC frequency in patients with different stages of CKD as well as the relationship between HHC and endothelial dysfunction and structural-functional status of the heart. The study involved 148 persons with different stages of CKD who underwent immunoenzyme determination of total plasma homocysteine (HC), echocardiography, carotid ultrasonograghy, endothelial function was assessed as well. It was found that among the patients with CKD, 26 (21.1%) had normal and 34 (27.7%) had subnormal HC levels, mild HHC was observed in 30 (24.4%) and moderate HHC – in 33 (26.8%) cases, i.e. the total number of patients with elevated HC level was 88.9%. It should be noted that no patients with normal HC level were found among those with stage four CKD as well as in dialysis patients. The increase of blood plasma HC level was actually proportional to the severity of renal failure, which in its turn led to the shift in the number of cases towards higher rank indices of HHC level. In particular, while there were no patients with HHC among those with CKD-I, more than 50% of such patients were found in the group with CKD-V. Reduced myocardial contractility and echocardiographic markers of left ventricular hypertrophy in patients with CKD were found to be closely associated with HC concentrations in blood plasma. The data presented clearly demonstrate strong inverse correlation between endothelial dysfunction indices and HC level. So, the endothelium-dependent brachial artery vasodilation in patients with CKD-IV was lower by 3.8 and 1.5 times compared with control group and CKD-III group, respectively, and endothelium-independent vasodilation of the brachial artery – by 2.4 and 1.9 times, respectively. Correlation analysis also confirmed that impaired endothelium-dependent and endothelium-independent dilation with high statistical significance inversely correlated with the level of HC in blood plasma. Thus, the population of patients with CKD is characterized by high HHC frequency, which is closely associated with cardiovascular disorders (endothelial dysfunction, structural and functional remodelling of the myocardium) and can be an important risk factor for the development of vascular lesions. We believe that adequate correction of HHC, including administration of folic acid preparations could reduce the progression of vascular lesions in patients with CKD.


Amin, A. P., Spertus, J. A., Reid, K. J., Lan, X., Buchanan, D. M., Decker, C., & Masoudi, F. A. (2010). The prognostic importance of worsening renal function during an acute myocardial infarction on long-term mortality. American Heart Journal, 60, 1065–1071.
Baszczuk, A., Kopczynski, Z., & Thielemann, A. (2014). Endothelial dysfunction in patients with primary hypertension and hyperhomocysteinemia. Postepy Higieny i Medycyny Doswiadczainej, 68, 91–100.
Chuang, C. H., Lee, Y. Y., Sheu, B. F., Hsiao, C. T., Loke, S. S., Chen, J. C., & Li, W. C. (2013). Homocysteine and C-reactive protein as useful surrogate markers for evaluating CKD risk in adults. Kidney Blood Pressure Research, 37, 402–413.
Dayal, S., Blokhin, I. O., Erger, R. A., Jensen, M., Arning, E., Stevens, J. W., Bottiglieri, T., Faraci, F. M., & Lentz, S. R. (2014). Protective vascular and cardiac effects of inducible nitric oxide synthase in mice with hyperhomocysteinemia. PLoS One, 9(9), e107734.
Fromot, J., Deharo, P., Bruzzese, L., Cuisset, T., Bonatti, S., Fenouillet, E., Motolla, G., Ruf, J., Guieu, R., & Can, J. (2016). Adenosine plasma level correlates with homocysteine and uric acid in patients with coronary artery disease. Physiology and Pharmacology, 94(3), 272–277.
Gangly, P., & Alam, S. F. (2015). Role of homocysteine in the development of cardiovascular disease. Nutrition Journal, 14, 6.
Hang, X., Yuling, Z., Yanjie, X., William, Y., Xiaohua, J., Xiaojin, S., Xiaoshu, C., Jingfeng, W., Xuebin, Q., Jun, Y., Yong, J., Xiaofeng, Y., & Hong, W. (2017). Caspase-1 inflammasome activation mediates homocysteine-induced pyrom-apoptosis in endotelial cells. Circulation Research, 118(10), 1525–1539.
Heilmann, R. M., Grutzner, N., Iazbik, M. C., Lopes, R., Bridges, C. S., Suchodolski, J. S., Couto. C. G., & Steiner, J. M. (2017). Hyperhomocysteinemia in Greyhounds and its association whith hypofolatemia and other clinicopatologic variables. Journal of Veterinary Internal Medicine, 31(1), 109–116.
Jacobsen, D. W. (1998). Homocysteine and vitamins in cardiovascular disease. Clinical Chemistry, 44, 1833–1843.
Kolarz, M., Glowacki, R., Stompor, T., Wyroslak, J., & Undas, A. (2012). Elevated levels of Nε-homocysteinyl-lysine isopeptide in patients on long-term hemodialysis. Clinical Chemistry and Laboratory Medicine, 50(8), 1373–1378.
Kolarz, M., Malyszko, J., Stompor, T., Calca, A., Undas, A., & Mysliwiec, M. (2013). Antibodies against Nε-homocysteinylated proteins in patients on different methods of renal replacement therapy. Clinical Chemistry and Laboratory Medicine, 51(5), 1093–1099.
Kolesnyk, M., Nicolaenko, S., & Snisar, L. (2016) Rating score medical care renal profile in Ukraine 2015. Ukrainian Journal of Nephrology and Dialysis, 4(52), 1–9.
Lai, S., Dimko, M., Galani, A., Coppola, B., Innico, G., Frassetti, N., Mazzei, E. D., & Mariotti, A. (2015). Early markers of cardiovascular risk in chronic kidney disease. Renal Failure, 37(2), 254–261.
Lai, W. K., & Kan, M. Y. (2015). Homocysteine-induced endothelial dysfunction. Annals of Nutrition and Metabolism, 67(1), 1–12.
Levi, A., Cohen, E., Levi, M., Golberg, E., Garty, M., & Krause, I. (2014). Elevated serum homocysteine is a predictor of accelerated decline in renal function and chronic kidney disease: A historical prospective study. European Journal of Internal Medicine, 25(10), 951–955.
Long, Y., & Nie, J. (2016). Homocysteine in renal injury. Kidney Diseases (Basel), 2(2), 80–87.
Matsushita, K., van der Velde, M., Astor, B. C., Woodward, M., Levey, A. S., de Jonq, P. E., Corech, J., & Gansevoort, R. T. (2010). Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: A collaborative meta-analysis. Lancet, 375(9731), 2073–2081.
Mazur, P., Kozynacka, A., Duraiski, L., Glowacki, R., Pfitzner, R., Fijorek, K., Sadovski, J., & Undas, A. (2012). Nɛ-homocysteinyl-lysine isopeptide is associated with progression of peripheral artery disease in patients treated with folic acid. European Journal of Vascular and Endovascular Surgery, 43(5), 588–593.
Neigwekar, S. U., Kang, A., Zoungas, S., Cass, F., Gallagher, M. P., Kulshrestha, S., Navaneethan, S. U., Perkovic, V., Strippoli, G. F., & Jardine, M. J. (2015). Interventions for lowering plasma homocysteine levels in dialysis patients. Cochrane Database of Systematic Reviews, 31(5), CD004683.
Pang, H., Han B., Fu, Q., & Zong, Z. (2016). Association of high homocysteine levels with the risk stratification in hypertensive patients at risk of stroke. Clinical Therapeutics, 38(5), 1184–1192.
Qin, X., Huo, Y., Xie, D., Hou, F., Xu, X., & Wang, H. (2013). Homocysteine-lowering therapy whith folic acid is effective in cardiovascular disease prevention in patients whith kidney disease: A meta-analysis of randomized controlled trials. Clinical Nutrition, 32(5), 722–727.
Rebrov, A. P., & Zelepukina, N. Y. (2001). Disfunction an endoteliya at patients with a chronic glomerulonefrit in various stages of a renal failure. Nephrology and Dialysis, 3(4), 33–36.
Toda, N., & Okamura, T. (2016). Huperhomocysteinemia impairs regional blood flow: Involvements of endothelial and neuronal nitric oxide. Pfugers Archiv, 468(9), 1517–1525.
Tyagi, N., Sedoris, K. S., Steed, M., Ovechkin, A. V., Moshai, K. S., & Tyagi, S. C. (2005). Mechanisms of homocysteine-induced oxidative stress. American Journal of Physiology Heart and Circulatory Physiology, 289(6), 2649–2656.
Xie, D., Yuan, Y., Guo, J., Yang, S., Xu, X., Wang, Q., Li, Y., Qin, X., Tang, G., Huo, Y., Deng, G., Wu, S., Wang, B., Zhang, Q., Wang, X., Fang, P., Wang, H., Xu, X., & Hou, F. (2015). Hyperhomocysteinemia predicts renal function decline: A prospective study in hypertensive adults. Scientific Reports, 5, 16268.
Yildiz, G., Duman, A., Aydin, H., Yilmaz, A., Hur, E., Magden, K., Cetin, G., & Candan, F. (2013). Evaluation of association between atherogenic index of plasma and intima-media thickness of the carotid artery for subclinic atherosclerosis in patients on maintenance hemodialysis. Hemodialysis International, 17(3), 397–405.
Zhang, D., Sun, X., Liu, J., Xie, X., Cui, W., & Zhu, Y. (2015). Homocysteine accelerates senescence of endothelial cells via DNA hypomethylation of human telomerase reverse transcriptase. Arteriosclerosis, Thrombosis and Vascular Biology, 35(1), 71–78.
How to Cite
Postovitenko, K., Iliuk, I., Shevchuk, S., Bezsmertna, G., BezsmertnyiІ., & Kurylenko, I. (2017). Hyperhomocysteinemia in patients with chronic kidney disease and its relationship with the functional status of the cardiovascular system. Regulatory Mechanisms in Biosystems, 8(2), 141-151. https://doi.org/https://doi.org/10.15421/021723