CLINICAL IMPORTANCE OF MARKERS OF RENAL DYSFUNCTION IN CARDIO-VASCULAR RISK STRATIFICATION

Purpose of the study. To study the significance of cystatin C of blood plasma and its relationship with central arterial pressure and carotid intima-media thickness (CIMT) in the stratification of cardiovascular risk.

Materials and methods. A general clinical and laboratory examination of 206 patients aged 16 to 88 years was performed, of which men were 101 (49%), women - 105 (51%). The mean age of the examined subjects was 51.8±14.3 years. Lipid spectrum parameters [total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C)], cystatin C, plasma uric acid and fibrinogen were studied. Glomerular filtration rate (GFR) was calculated using the F.J. Hoek et al. (2003) formula. To assess the central blood pressure, all patients underwent a contour analysis of the pulse wave on the AngioScan-01 (AngioScan-Electronics, Russia) and ultrasound examination of carotid artery (CA) on Vivid Q (USA). The type of research was single-step cross-sectional. Depending on the content of cystatin C of the blood plasma, all the examined subjects were divided into three groups. Group 1 (n=62) consisted of patients with cystatin C concentration of up to 0.99 mg/l; group 2 (n=91) - from 1.0 mg/l to 1.5 mg/l; group 3 (n=53) - over 1.51 mg/l.

Results. Patients with excessive body weight, stable angina, type 2 diabetes, cerebrovascular diseases (CVD) and chronic glomerulonephritis (CGN) significantly prevailed in group 3, in comparison with groups 1 and 2 (p<0.5). Mean levels of systolic and central blood pressure (BP) were significantly higher in patients from group 3 (p<0.05). In the same group, there was a significant decrease in HDL cholesterol level (p<0.05), an increase in TG concentration (p<0.05), and blood plasma uric acid (p<0.05), as well as CIMT. Statistically and clinically significant decrease in GFR and an increase in the level of cystatin C in blood plasma was noted both in groups 2 and 3 (p<0.05). Positive correlation between CIMT and the level of cystatin C of blood plasma (r=0.578, p<0.05) and negative correlation with the value of GFR (r=-0.556, p<0.05) were recorded among the patients of group 1. In group 2, strong correlation was observed between CIMT and the content of HDL cholesterol plasma (r=-0.343; p<0.05). A significant direct relationship between CIMT and systolic level (r=0.482, p<0.05) and central arterial pressure (r=0.479, p<0.05) was found in individuals from group 3.

Conclusion. Studying the content of cystatin C of blood plasma in conjunction with determination of GFR is a priority for early diagnosis of renal dysfunction and assessment of cardiovascular disorders, providing stratification of groups of cardiovascular risk and subsequent implementation of preventive measures to reduce the level of total cardiovascular risk.

1. Moiseev V.S., Mukhin N.A, Smirnov A.V. Cardiovascular risk and chronic kidney disease: cardio-nephroprotection strategies. Russian Journal of Cardiology. 2014;8:7-37. doi:10.15829/1560-4071-2014-8-7-37 [in Russian].

2. Di Lullo L., Gorini A., Russo D. et al. Left ventricular hypertrophy in chronic kidney disease patients: from pathophysiology to treatment. Cardiorenal medicine. 2015; 5(4):254-266. doi:https://doi.org/10.1159/000435838.

3. Foley R.N., Parfrey P.S., Harnett J.D. et al. The prognostic importance of left ventricular geometry in uremic cardiomyopathy. J Am Soc Nephrol. 1995; 5:2024-2031. PMID:7579050.

4. Mukhin N.A., Glybochko P.V., Svistunov A.A. et al.Chronic kidney disease and atrial fibrillation as components cardiorenal continuum. Therapeutic Archives. 2016;6:4-8. doi:10.17116/terarkh20168864-8. [in Russian].

5. Chazova I.E., Zhernakova Iu.V., Oshchepkova E.V. et al. Rasprostranennost' faktorov riska razvitiia serdechnososudistykh zabolevanii v rossiiskoi populiatsii bol'nykh arterial'noi gipertoniei. Kardiologiia. 2014; 10:4-12. [in Russian]

6. Shilo V.Yu., Zemchenkov A.Yu., Gurevich K.Ya. et al. Russian national guidelines for the diagnosis and treatment of anemia in chronic kidney disease. Nephrology and Dialysis. 2016;18(1):19-34. [in Russian]

7. Astor B.C., Muntner P., Levin A. et al. Association of kidney function with anemia: the Third National Health and Nutrition Examination Survey (1988–1994). Arch. Intern. Med.2002; 162:1401–1408. PMID:12076240.

8. Bobkova I.N., Shchukina A.A., Shestakova M.V. Аssessment of nephrin and podocin levels in the urine of patients with diabetes mellitus. Nephrology. 2017;21(2):33-40. [in Russian]

9. Fuhrman D.Y., Schneider M.F., Dell K.M. et al. Albuminuria, proteinuria, and renal disease progression in children with CKD. Clinical Journal of the American Society of Nephrology. 2017; 6:912-920. CJN. 11971116.

10. Tsimihodimos V., Mitrogianni Z., Elisaf M. Dyslipidemia associated with chronic kidney disease. The open cardiovascular medicine journal. 2011; 5:С.41-48. doi:10.2174/1874192401105010041.

11. Visconti L., Benvenga S., Lacquaniti A. et al. Lipid disorders in patients with renal failure: Role in cardiovascular events and progression of chronic kidney disease.Journal of Clinical & Translational Endocrinology. 2016;6:8-14. doi:10.1016/j.jcte.2016.08.002.

12. Murkamilov I.T., Sabirov I.S., Fomin V.V. et al. Hyperuricemia in chronic glomerulonephritis: clinical and functional features. Clinical nephrology. 2018;1:31-37. [in Russian]

13. Ramirez-Sandoval J.C., Madero M. Treatment of Hyperuricemia in Chronic Kidney Disease. Uric Acid in Chronic Kidney Disease. Karger Publishers. 2018;192:135-146. doi:https://doi.org/10.1159/000484288

14. Whitfield J. B. Genetic insights into cardiometabolic risk factors. The Clinical Biochemist Reviews. 2014; 35(1):15-36. PMID: 24659834

15. Mukhin N.A.Nephrology.Nationalleadership. QuickEdition. 2016; 608 p. [in Russian]

16. Kon V., Linton M.R.F., Fazio S. Atherosclerosis in chronic kidney disease: the role of macrophages.Nature Reviews Nephrology. 2011;7(1):45-54. doi: 10.1038/nrneph.2010.157

17. Anichkov N.N. On the etiology and pathogenesis of atherosclerosis. Archives of Biol. sciences. 1935;9:51-85. [in Russian]

18. Bundy J.D., Chen J., Yang W. et al. Risk factors for progression of coronary artery calcification in patients with chronic kidney disease: The CRIC study. Atherosclerosis. 2018;271:53–60. doi: https://doi.org/10.1016/j.atherosclerosis.2018.02.009

19. Bozic M., Méndez-Barbero N., Gutiérrez-Muñoz C. et al. Combination of biomarkers of vascular calcification and sTWEAK to predict cardiovascular events in chronic kidney disease. Atherosclerosis. 2018;270:13-20. doi:10.1016/j.atherosclerosis.2018.01.011.

20. Sikri T., Chander R., Singh P. et al. Correlation of carotid intimalmedial thickness with estimated glomerular filtration rate and cardiovascular risk factors in patients of chronic kidney disease. Journal of evolution of medical and dental sciences-jemds. 2017;6(3):202-206. DOI: 10.14260/Jemds/2017/47.

21. Kokubo Y., Watanabe M., Higashiyama A. et al. Impact of Intima-Media Thickness Progression in the Common Carotid Arteries on the Risk of Incident Cardiovascular Disease in the Suita Study. J Am Heart Assoc. 2018;1;7(11). pii: e007720. doi: 10.1161/JAHA.117.007720.

22. Lorenz M.W., Gao L., Ziegelbauer K. et al. Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration. PLoS One. 2018;12.13(4):e0191172. doi: 10.1371/journal.pone.0191172.

23. Hoek F.J., Kemperman F.A., Krediet R.T. A comparison between cystatin C, plasma creatinine and the Cockcroft and Gault formula for the estimation of glomerular fi ltration rate. Nephrol Dial Transplant. 2003; 18(10):2024-2031.doi:10.1093/ndt/gfg349.

24. Parfenov AS. Early diagnosis of cardiovascular diseases using hardware-software complex "Аngioscan -01". Poliklinika.2012;2:1:70-74. [in Russian]

25. Mancia G., De Backer G., Dominiczak A. et al. The task force for the management of arterial hypertension of the European Society of Hypertension, The task force for the management of arterial hypertension of the European Society of Cardiology. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2007;28(12):1462–

26. doi:https://doi.org/10.1093/eurheartj/ehm236

27. Methods of statistical processing of medical data: Methodological recommendations for residents and graduate students of medical schools, researchers / comp.: Kochetov A.G., Lyang O.V., Masenko V.P., Zhirov I.V., Nakonechnikov S.N., S.N. Tereshchenko - M.: RKNPK, 2012. – 42 p. [in Russian]

28. Kuvshinova O.A. Problems of social construct of the elderly. Bulletin of Tomsk State University. Philosophy. Sociology. Political science. 2012;1(17):24-30. [in Russian]

29. Bosevski M., Stojanovska L. Risk Factors for Carotid Artery Disease and Chronic Kidney Disease: Same or Unique?. Therapeutic Apheresis and Dialysis. 2018. doi:https://doi.org/10.1111/1744-9987.12667

30. Figurek A., Spasovski G., Popovic‐Pejicic S. FGF23 Level and Intima‐Media Thickness Are Elevated From Early Stages of Chronic Kidney Disease. Therapeutic Apheresis and Dialysis. 2018;22(1):40-48. doi:https://doi.org/10.1111/1744-9987.12592

31. Shah A.S., Dabelea D., Fino N.F. et al. Predictors of increased carotid intima media thickness in youth with type 1 diabetes: the SEARCH CVD study. Diabetes care.2015.С.dc151963. doi:https://doi.org/10.2337/dc15-1963

32. Liu B., Ni J., Shi M. et al. Carotid Intima-media Thickness and its Association with Conventional Risk Factors in Low-income Adults: A Population-based Cross-Sectional Study in China. Scientific reports. 2017;7:41500. doi: 10.1038/srep41500.

33. Safar M.E., Levy B.I., Struijker-Boudier H. Current рerspectives on аrterial stiffness and pulse pressure in hypertension and cardiovascular diseases. Curculation.2003;10(22):2864-2869. doi: https://doi.org/10.1161/01.CIR.0000069826.36125.B4

34. Kieltyka L., Urbina E., Tang R. Framingham risk score to carotid intima-media thickness in both white and black young adult: the Bogalusa Heart Study. Aterosclerosis. 2003;170(1):125-130.

35. doi:https://doi.org/10.1016/S0021-9150(03)00244-2

36. Laurent S., Cockroft J., Bortel L. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur. Heart J. 2006;27(1):2588-2605.doi:https://doi.org/10.1093/eurheartj/ehl254

37. Bashuk V.V., Anosova E.V., Prashchayeu K.I. et al. The intimamidia complex as new morphofunctional object for investigation of processes of polymorridity. Scientific bulletins. Series Medicine. Pharmacy. 2013. No. 4 (147). Issue 21/1. C.22-27. [in Russian]

38. Chambless L.E., Folsom A.R., Davis V. et al. Risk factors for progression of com- mon carotid atherosclerosis: the Atherosclerosis Risk in Communities Study, 1987–1998. Am J Epidemiol. 2002;155(1):38–47. PMID:11772783

39. Salonen R., Salonen J.T. Progression of carotid atherosclerosis and its determinants: a population-based ultrasonography study. Atherosclerosis. 1990;81(1):33–40. PMID:2407252

40. Murkamilov I.T., Aitbaev R.A., Fomin V.V., Yusupov F.A. Subclinical lesion of carotid arteries in chronic glomerulonephritis. The Russian Archives of Internal Medicine. 2017;7(4):300-305. doi:https://doi.org/10.20514/2226-6704-2017-7-4-300-305. [in Russian]

41. Murkamilov I.T., Aitbaev K.A., Sarybaev A.Sh. et al. Relationship of Remodeling of carotid Arteries and Left Ventricular Geometry in Patients With Chronic Glomerulonephritis. Kardiologiia. 2018;58(4):45-52. doi:10.18087/cardio.2018.4.10108. [in Russian]

42. Safar M.E., Blacher J., Pannier B. et al. Central Pulse Pressure and Mortality in End-Stage Renal Disease Hypertension. 2002;39:735-738. PMID:11897754

43. Ohno Y., Kanno Y., Takenaka T. Central arterial pressure and chronic kidney disease.World journal of nephrology. 2016;5(1):90-100. doi:10.5527/wjn.v5.i1.90

44. Rahman M., Hsu J.Y., Desai N. et al. Central Arterial pressure and Cardiovascular Outcomes in Chronic Kidney Disease. Clinical Journal of the American Society of Nephrology. 2018.С. CJN. 08620817. doi:10.2215/CJN.08620817

45. Townsend R.R. Arterial Stiffness in CKD: A Review. Am J Kidney Dis. 2018.pii: S0272-6386(18)30649-8. doi:10.1053/j.ajkd.2018.04.005.

46. Kong X., Ma X., Tang L. et al. Arterial stiffness evaluated by carotid-femoral pulse wave velocity increases the risk of chronic kidney disease in a Chinese population-based cohort. Nephrology (Carlton). 2017;22(3):205-212. doi:10.1111/nep.12750

47. Kuczera P., Kwiecień K., Adamczak M. et al. Different Relevance of Peripheral, Central or Nighttime Arterial pressure Measurements in the Prediction of Chronic Kidney Disease Progression in Patients with Mild or No-Proteinuria. Kidney and Arterial pressure Research. 2018;43(3):735-743.

48. Mastanvalli B., Kumar K.P., Madhav D.et al. Evaluation of arterial stiffness in nondiabetic chronic kidney disease patients.Saudi Journal of Kidney Diseases and Transpla ntation.2017;28(1):61-67. doi:http://www.sjkdt.org/text.asp?2017/28/1/61/198136

49. Krishnasamy R., Tan S.J., Hawley C.M. et al. Progression of arterial stiffness is associated with changes in bone mineral markers in advanced CKD.BMC nephrology.2017;18(1):281. doi:https://doi.org/10.1186/s12882-017-0705-4

50. Zhao R., Li Y., Dai W. Serum cystatin C and the risk of coronary heart disease in ethnic chinese patients with normal renal function.Laboratory medicine. 2016;47(1):13-19. doi: https://doi.org/10.1093/labmed/lmv004

51. Ayu Ogawa-Akiyama et al. Serum cystatin C is an independent biomarker associated with the renal resistive index in patients with chronic kidney disease. PLOS ONE. 2018;13(3):Р. e0193695.

52. Mayanskaya S.D., Grebenkina I.A., Oshchepkova O.B., Mihoparova O.J. Intima-media thickness of common carotid artery as an early predictor of arterial hypertension in patients with hereditary load. The Bulletin of Contemporary Clinical Medicine. 2016;9(6):67-72. doi:10.20969/VSKM.2016.9(6).67-72 [in Russian]

53. Wang F., Xiong R., Feng S. et al. Association of Circulating Levels of ADMA with Carotid Intima-Media Thickness in Patients with CKD: a Systematic Review and Meta-Analysis. Kidney and Arterial pressure Research. 2018;43(1):25-33.

54. Kobayashi T., Yokokawa H., Fujibayashi K. et al. Association between high cystatin C levels and carotid atherosclerosis. World journal of cardiology. 2017; 9(2):174-181.doi: 10.4330/wjc.v9.i2.174

55. Chhajed N., Chandra B.S., Shetty M.S., & Shetty C. Correlation of carotid intimal-medial thickness with estimated glomerular filtration rate and cardiovascular risk factors in chronic kidney disease. Saudi Journal of Kidney Diseases and Transplantation. 2014; 25(3):572-576. doi:http://www.sjkdt.org/text.asp?2014/25/3/572/132186