Risk factors for cardiovascular complications in chronic kidney disease

Risk factors are constitutional peculiarity and human behavior that infl uence the disease development and / or pathological condition in the future. With regard to certain nosological units, including cardiovascular diseases, modifi able and nonmodifi able risk factors are distinguished. Non-modifi able risk factors for the development and progression of cardiovascular diseases include age, gender, and genetic predisposition, which are used to develop risk stratifi cation systems. These risk factors cannot be adjusted, ie. modifi ed, and can only be taken into account when determining the level of risk of diseases development. On the contrary, modifi able risk factors can undergo changes and be subdivided into behavioral and biological ones. Behavioral risk factors include: smoking, unhealthy diet, low physical activity, excessive alcohol consumption, chronic psycho-emotional stress. These behavioral risk factors in the lifestyle of a modern person are becoming more common in the conditions of urbanization, and contribute to the development of cardiovascular diseases. It should be noted that with longterm exposure to behavioral risk factors on the human body, biological risk factors are also formed: arterial hypertension, dyslipidemia, overweight, obesity, diabetes mellitus, chronic kidney disease.This review discusses the contribution of chronic kidney disease as a risk factor, as well as the mechanisms of formation and progression of cardiovascular diseases in kidney dysfunction.

1. Cardiovascular diseases. World Health Organization, 2020. [Electronic resource]. URL: https://www.who.int/health-topics/cardiovascular-diseases/#tab=tab_1. Accessed: 20 Jan 2021.

2. Bunova S., Okhotnikova P., Skirdenko Yu. et al. COVID-19 and cardiovascular comorbidity: the search for new approaches to reduce mortality. Cardiovascular therapy and prevention. 2021;20(4):2953. (In Russian). DOI: 10.15829/1728-8800-2021-2953

3. Hill N., Fatoba S. Oke J. et al. Global prevalence of chronic kidney disease — a systematic review and meta-analysis. PLoS One. 2016;11(7):e0158765. DOI: 10.1371/journal.pone.0158765

4. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classifi cation, and stratifi cation. Am. J. Kidney Dis. 2002;39(1):S1–S266.

5. Zalups R., Diamond G. Mercuric chloride-induced nephrotoxicity in the rat following unilateral nephrectomy and compensatory renal growth. Virchows Arch. B Cell Pathol. Incl. Mol. Pathol. 1987;53(6):336–46. DOI: 10.1007/BF02890261

6. Parikh N., Hwang S., Larson M. et al. Cardiovascular disease risk factors in chronic kidney disease: overall burden and rates of treatment and control. Arch. Intern. Med. 2006;166(17):1884–91. DOI: 10.1001/archinte.166.17.1884

7. Coresh J., Astor B., Greene T. et al. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am. J. Kidney Dis. 2003;41(1):1–12. DOI: 10.1053/ajkd.2003.50007

8. Go A., Chertow G., Fan D. et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N. Engl. J. Med. 2004;351:1296–1305. DOI: 10.1056/NEJMoa041031

9. Kerr M., Bray B., Medcalf J. et al. Estimating the financial cost of chronic kidney disease to the NHS in England. Nephrology Dialysis Transplantation. 2012;27(3):73–80.

10. Chronic Kidney Disease Prognosis Consortium, Matsushita K., van der Velde M., Astor B. et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet. 2010;375(9731):2073–81. DOI: 10.1016/S0140-6736(10)60674-5

11. Hippisley-Cox J., Coupland C., Vinogradova Y. et al. Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2. BMJ. 2008;336(7659):1475–82. DOI: 10.1136/bmj.39609.449676.25

12. Goff D.Jr., Lloyd-Jones D., Bennett G. et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J. Am. Coll. Cardiol. 2014;63(25 Pt B):2935–2959. DOI: 10.1016/j.jacc.2013.11.005

13. Tangri N., Kitsios G., Inker L. et al. Risk prediction models for patients with chronic kidney disease: a systematic review. Ann. Intern. Med. 2013;158(8):596–603. DOI: 10.7326/0003-4819-158-8-201304160-00004

14. Major R., Cheng M., Grant R. et al. Cardiovascular disease risk factors in chronic kidney disease: A systematic review and meta-analysis. PLoS ONE. 2018;13(3):e0192895. DOI: 10.1371/journal.pone.0192895

15. Matsushita K., Coresh J., Sang Y. et al. Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data. Lancet Diabetes Endocrinol. 2015;3:514–525. DOI: 10.1016/S2213-8587(15)00040-6

16. Schiffrin E., Lipman M., Mann J. Chronic kidney disease: effects on the cardiovascular system. Circulation. 2007;116:85–97. DOI: 10.1161/CIRCULATIONAHA.106.678342

17. Menon V., Gul A., Sarnak M. Cardiovascular risk factors in chronic kidney disease. Kidney Int. 2005;68(4):1413–1418. pmid:16164615.

18. Covic A., Kothawala P., Bernal M. et al. Systematic review of the evidence underlying the association between mineral metabolism disturbances and risk of all-cause mortality, cardiovascular mortality and cardiovascular events in chronic kidney disease. Nephrol. Dial. Transplant. 2009;24(5):1506–1523. pmid:19001560.

19. London G., Pannier B., Guerin A. et al. Alterations of left ventricular hypertrophy in and survival of patients receiving hemodialysis: follow-up of an interventional study. J. Am. Soc. Nephrol. 2001;12(12):2759–2767. DOI: 10.1681/ASN.V12122759

20. Chen S., Huang J., Su H. et al. Prognostic cardiovascular markers in chronic kidney disease. Kidney Blood Press Res. 2018;43:1388–1407. DOI: 10.1159/000492953

21. Cottone S., Lorito M., Riccobene R. et al. Oxidative stress, inflammation and cardiovascular disease in chronic renal failure. J. Nephrol. 2008;21(2):175–9. pmid: 18446711.

22. Oishi Y., Manabe I. Macrophages in age-related chronic inflammatory diseases. NPJ Aging Mech. Dis. 2016;2:16018. DOI: 10.1038/npjamd.2016.18

23. Silverstein D. Inflammation in chronic kidney disease: role in the progression of renal and cardiovascular disease. Pediatr. Nephrol. 2009;24:1445–1452. DOI: 10.1007/s00467-008-1046-0

24. Sproston N., Ashworth J. Role of C-reactive protein at sites of inflammation and infection. Front. Immunol. 2018;9:754. DOI: 10.3389/fimmu.2018.00754

25. Stenvinkel P., Larsson T. Chronic kidney disease: a clinical model of premature aging. Am. J. Kidney Dis. 2013;62:339–351. DOI: 10.1053/j.ajkd.2012.11.051

26. Wu I., Hsu K., Lee C. et al. p-Cresyl sulphate and indoxyl sulphate predict progression of chronic kidney disease. Nephrol. Dial. Transplant. 2011;26:938–947. DOI: 10.1093/ndt/gfq580

27. Ramezani A., Raj D. The gut microbiome, kidney disease, and targeted interventions. J. Am. Soc. Nephrol. 2014;25:657–670. DOI: 10.1681/ASN.2013080905

28. Sirich T., Meyer T., Gondouin B. et al. Protein-bound molecules: a large family with a bad character. Semin. Nephrol. 2014;34:106–117. DOI: 10.1016/j.semnephrol.2014.02.004

29. Sies H. Biochemistry of Oxidative Stress. Angew. Chem. Int. Ed. Engl. 1986;25:1058–1071. DOI: 10.1002/anie.198610581

30. Cachofeiro V., de Goicochea M., Vinuesa S. et al. Oxidative stress and inflammation, a link between chronic kidney disease and cardiovascular disease. Kidney Int. 2008;74:S4–S9. DOI: 10.1038/ki.2008.516

31. Mihai S., Codrici E., Popescu I. et al. Inflammation-related mechanisms in chronic kidney disease prediction, Progression, and outcome. J. Immunol. Res. 2018:2180373. DOI: 10.1155/2018/2180373

32. Liakopoulos V., Roumeliotis S., Zarogiannis S. et al. Oxidative stress in hemodialysis: causative mechanisms, clinical implications, and possible therapeutic interventions. Semin. Dial. 2019;32:58–71. DOI: 10.1111/sdi.12745

33. Merino A., Buendia P., Martin-Malo A. et al. Senescent CD14+CD16+ monocytes exhibit proinflammatory and proatherosclerotic activity. J. Immunol. 2011;186:1809–1815. DOI: 10.4049/jimmunol.1001866

34. Carracedo J., Alique M., Ramirez-Carracedo R. et al. Endothelial extracellular vesicles produced by senescent cells: pathophysiological role in the cardiovascular disease associated with all types of diabetes mellitus. Curr. Vasc. Pharmacol. 2018;17:447–454. DOI: 10.2174/1570161116666180820115726

35. López-Otín C., Blasco M., Partridge L. et al. The hallmarks of aging. Cell. 2013;153:1194–1217. DOI: 10.1016/j.cell.2013.05.039

36. Shimizu I., Minamino T. Cellular senescence in cardiac diseases. J. Cardiol. 2019;74:313–319. DOI: 10.1016/j.jjcc.2019.05.002

37. Stenvinkel P., Larsson T. Chronic kidney disease: a clinical model of premature aging. Am. J. Kidney Dis. 2013;62:339–351. DOI: 10.1053/j.ajkd.2012.11.051

38. Popolo A., Autore G., Pinto A., Marzocco S. Oxidative stress in patients with cardiovascular disease and chronic renal failure. Free Radic. Res. 2013;47:346–356. DOI: 10.3109/10715762.2013.779373

39. Currie G., Delles C. Proteinuria and its relation to cardiovascular disease. International journal of nephrology and renovascular disease. 2013;7:13–24. DOI:10.2147/IJNRD.S40522

40. Wagner D., Harris T., Madans J. Proteinuria as a biomarker: risk of subsequent morbidity and mortality. Environ. Res. 1994;66(2):160–72. DOI: 10.1006/enrs.1994.1052

41. Hillege H., Janssen W., Bak A. et al. Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity. J. Intern. Med. 2001;249(6):519–26. DOI: 10.1046/j.1365-2796.2001.00833.x

42. Wachtell K., Ibsen H., Olsen M. et al. Albuminuria and cardiovascular risk in hypertensive patients with left ventricular hypertrophy: the LIFE study. Ann. Intern. Med. 2003;139(11):901–6. DOI: 10.7326/0003-4819-139-11-200312020-00008

43. Lee M., Saver J., Chang K. et al. Impact of microalbuminuria on incident stroke: a meta-analysis. Stroke. 2010;41(11):2625–31. DOI: 10.1161/STROKEAHA.110.581215

44. Deckert T., Feldt-Rasmussen B., Borch-Johnsen K. et al. Albuminuria refl ects widespread vascular damage. The Steno hypothesis. Diabetologia. 1989;32(4):219–26. DOI: 10.1007/BF00285287

45. Hellemons M., Lambers Heerspink H., Gansevoort R. et al. Highsensitivity troponin T predicts worsening of albuminuria in hyper tension; results of a nested case-control study with confirmation in diabetes. J. Hypertens. 2013;31(4):805–12. DOI: 10.1097/HJH.0b013e32835eb5e8

46. Yilmaz M., Sonmez A., Saglam M. et al. ADMA levels correlate with proteinuria, secondary amyloidosis, and endothelial dysfunction. J. Am. Soc. Nephrol. 2008;19(2):388–95. DOI: 10.1681/ASN.2007040461

47. Stehouwer C., Gall M., Twisk J. et al. Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: progressive, interrelated, and independently associated with risk of death. Diabetes. 2002;51(4):1157–65. DOI: 10.2337/diabetes.51.4.1157

48. Hirano T., Kashiwazaki K., Moritomo Y. et al. Albuminuria is directly associated with increased plasma PAI-1 and factor VII levels in NIDDM patients. Diabetes Res. Clin. Pract. 1997;36(1):11–8. DOI: 10.1016/s0168-8227(97)01384-3

49. Mykkänen L., Zaccaro D., Wagenknecht L. et al. Microalbuminuria is associated with insulin resistance in nondiabetic subjects: the insulin resistance atherosclerosis study. Diabetes. 1998;47(5):793–800. DOI: 10.2337/diabetes.47.5.793

50. Bianchi S., Bigazzi R., Valtriani C. et al. Elevated serum insulin levels in patients with essential hypertension and microalbuminuria. Hypertension. 1994;23(6 Pt 1):681–7. DOI: 10.1161/01.hyp.23.6.681

51. Pinto-Sietsma S., Navis G., Janssen W. et al. A central body fat distribution is related to renal function impairment, even in lean subjects. Am. J. Kidney Dis. 2003;41(4):733–41. DOI: 10.1016/s0272-6386(03)00020-9

52. Fort J. Chronic renal failure: a cardiovascular risk factor. Kidney Int. Suppl. 2005;(99):S25–9. DOI: 10.1111/j.1523-1755.2005.09906.x

53. Zhou C., Shi Z., Ouyang N., Ruan X. Hyperphosphatemia and Cardio vascular Disease. Front Cell Dev. Biol. 2021;9:644363. DOI: 10.3389/fcell.2021.644363

54. Takashi Y., Fukumoto S. Fibroblast growth factor receptor as a potential candidate for phosphate sensing. Curr. Opin. Nephro.l Hypertens. 2020;29(4):446–452. DOI: 10.1097/MNH.0000000000000618

55. Yilmaz M., Saglam M., Caglar K. et al. The determinants of endothelial dysfunction in CKD: Oxidative stress and asymmetric dimethylarginine. Am. J. Kidney Dis. 2006;47:42–50. DOI: 10.1053/j.ajkd.2005.09.029

56. Vanhoutte P., Zhao Y., Xu A., Leung S. Thirty Years of Saying NO: Sources, Fate, Actions, and Misfortunes of the Endothelium-Derived Vasodilator Mediator. Circ. Res. 2016;119:375–396. DOI: 10.1161/CIRCRESAHA.116.306531

57. Zoccali C. Endothelial dysfunction and the kidney: Emerging risk factors for renal insufficiency and cardiovascular outcomes in essential hypertension. J. Am. Soc. Nephrol. 2006;17:561–563. DOI: 10.1681/ASN.2005121344

58. Milovanova L.Yu., Beketov V.D., Milovanova S.Yu., Taranova M.V., Filippova A.A., Pasechnik A.I. Biomarkers of damage to the heart and blood vessels in the framework of mineral and bone disorders in chronic kidney disease, the possibility of correction. Clinical medicine. 2021;99(4):245–258. (In Russian). DOI: 10.30629/0023-2149-2021-99-4-245-258