Rational Pharmacotherapy in Cardiology

Advanced search


Full Text:


Chronic kidney disease (CKD) is associated with increased cardiovascular risk. CKD is characterized by accelerated aging of vessels in which the age-related arterial stiffness increase is exacerbated by a number of uremia-related processes. Increased arterial stiffness is associated with structural and functional disorders, as well as with the increase in cardiovascular mortality in patients with CKD. Increased arterial stiffness is diagnosed at an early stage of CKD. Modern understanding of the mechanisms of increased risk of cardiovascular complications in CKD, the factors contributing to the loss of elasticity of the arteries, arterial stiffness increase consequences are analyzed. Data illustrating the twoway interaction between CKD and arterial stiffness and mechanisms of accelerated progression of arterial stiffness in CKD are presented.

About the Authors

J. D. Kobalava
Peoples' Friendship University of Russia, Moscow
Russian Federation

Yu. V. Kotovskaya
Peoples' Friendship University of Russia, Moscow
Russian Federation

S. V. Villevalde
Peoples' Friendship University of Russia, Moscow
Russian Federation

A. E. Soloveva
Peoples' Friendship University of Russia, Moscow
Russian Federation

I. M. Amirbegishvili
Peoples' Friendship University of Russia, Moscow
Russian Federation


1. Colin D., Jonathan N., Richard P., et al. Arterial stiffness in chronic kidney disease: causes and consequences. Heart 2010; 96: 817-23.

2. 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: 1296-305.

3. Van Biesen W., De Bacquer D., Verbeke F., et al. The glomerular filtration rate in an apparently healthy population and its relation with cardiovascular mortality during 10 years. Eur Heart J 2007; 28: 478-83.

4. Coresh J., Selvin E., Stevens L., et al. Prevalence of chronic kidney disease in the United States. JAMA 2007; 298: 2038-2047.

5. Levey A., Eckardt K., Tsukamoto Y., et al. Definition and classification of chronic kidney disease: a position statement from kidney disease: improving global outcomes (KDIGO). Kidney Int 2005; 67: 2089-100.

6. United States renal data system, Annual data report 2006. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2006.

7. van Popele N., Grobbee D., Bots M. et al. Association between arterial stiffness and atherosclerosis: the rotterdam study. Stroke 2001; 32: 454-60.

8. Cecelja M., Chowienczyk P. Dissociation of aortic pulse wave velocity with risk factors for cardiovascular disease other than hypertension. a systematic review. Hypertension 2009; 54: 1328-36.

9. Franklin S., Gustin W., Wong N. et al. Hemodynamic patterns of age-related changes in blood pressure. The framingham heart study. Circulation 1997; 96: 308-15.

10. Baksi A., Treibel T., Davies J. et al. A Meta-analysis of the mechanism of blood pressure change with aging. J Am Coll Cardiol 2009; 54: 2087-92.

11. Chen C., Nakayama M., Nevo E. et al. Coupled systolic-ventricular and vascular stiffening with age: implications for pressure regulation and cardiac reserve in the elderly. J Am Coll Cardiol 1998; 32: 1221-7.

12. Hundley W., Kitzman D., Morgan T. et al. Cardiac cycle-dependent changes in aortic area and distensibility are reduced in older patients with isolated diastolic heart failure and correlate with exercise intolerance. J Am Coll Cardiol 2001; 38: 796-802.

13. Edwards N., Ferro C., Townend J. et al. Aortic distensibility and arterialventricular coupling in early chronic kidney disease: a pattern resembling heart failure with preserved ejection fraction. Heart 2008; 94:1038-43.

14. Edwards N., Hirth A., Ferro C. et al. Subclinical abnormalities of left ventricular myocardial deformation in early-stage chronic kidney disease: the precursor of uremic cardiomyopathy? J Am Soc Echocardiogr 2008; 21: 1293-8.

15. Laurent S., Cockcroft J., Van Bortel L. et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 2006; 27: 2588-605.

16. Dovinova I., Cacanyiova S., Faberova V. et al. The effect of an NO donor, pentaerythrityl tetranitrate, on biochemical, functional, and morphological attributes of cardiovascular system of spontaneously hypertensive rats. Gen Physiol Biophys 2009; 28: 86-93.

17. Amann K., Wolf B., Nichols C. et al. Aortic changes in experimental renal failure: hyperplasia or hypertrophy of smooth muscle cells? Hypertension 1997; 29: 770-5.

18. Schwarz U., Buzello M., Ritz E. et al. Morphology of coronary atherosclerotic lesions in patients with end-stage renal failure. Nephrol Dial Transplant 2000; 15: 218-23.

19. Chung A., Yang H., Radomski M. et al. Long-term doxycycline is more effective than atenolol to prevent thoracic aortic aneurysm in marfan syndrome through the inhibition of matrix metalloproteinase- 2 and -9. Circ Res 2008; 102: 73-85.

20. Chung A., Yang H., Kim J. et al. Upregulation of matrix metalloproteinase-2 in the arterial vasculature contributes to stiffening and vasomotor dysfunction in patients with chronic kidney disease. Circulation 2009; 120: 792-801.

21. Konova E., Baydanoff S., Atanasova M. et al. Age-related changes in the glycation of human aortic elastin. Exp Gerontol 2004; 39: 249-54.

22. Makita Z., Radoff S., Rayfield E. et al. Advanced glycosylation end products in patients with diabetic nephropathy. N Engl J Med 1991; 325: 836-42.

23. Schwedler S., Metzger T., Schinzel R. et al. Advanced glycation end products and mortality in hemodialysis patients. Kidney Int 2002; 62: 301-10.

24. Ueno H., Koyama H., Tanaka S. et al. Skin autofluorescence, a marker for advanced glycation end product accumulation, is associated with arterial stiffness in patients with end-stage renal disease. Metabolism 2008; 57: 1452-7.

25. Kass D., Shapiro E., Kawaguchi M. et al. Improved arterial compliance by a novel advanced glycation end-product crosslink breaker. Circulation 2001; 104: 1464-70.

26. Zieman S., Melenovsky V., Clattenburg L. et al. Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension. J Hypertens 2007; 25: 577-83.

27. Thambyrajah J., Landray M., McGlynn F. et al. Abnormalities of endothelial function in patients with predialysis renal failure. Heart 2000; 83: 205-9.

28. Vallance P., Leone A., Calver A. et al. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 1992; 339: 572-5.

29. Bode-Boger S., Scalera F., Kielstein J. et al. Symmetrical dimethylarginine: a new combined parameter for renal function and extent of coronary artery disease. J Am Soc Nephrol 2006; 17: 1128-34.

30. Zoccali C., Benedetto F., Maas R. et al. Asymmetric dimethylarginine, C-reactive protein, and carotid intima-media thickness in end-stage renal disease. J Am Soc Nephrol 2002; 13: 490-6.

31. Vuurmans T., Boer P., Koomans H. Effects of endothelin-1 and endothelin-1 receptor blockade on cardiac output, aortic pressure, and pulse wave velocity in humans. Hypertension 2003; 41: 1253-8.

32. Dhaun N., Macintyre I., Melville V. et al. Blood pressure-independent reduction in proteinuria and arterial stiffness after acute endothelin-a receptor antagonism in chronic kidney disease. Hypertension 2009; 54: 113-9.

33. Weber M., Black H., Bakris G. et al. A selective endothelin-receptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension: a randomised, double-blind, placebo-controlled trial. Lancet 2009; 374: 1423-31.

34. Tepel M., van der Giet M., Statz M. et al. The antioxidant acetylcysteine reduces cardiovascular events in patients with end-stage renal failure: a randomized, controlled trial. Circulation 2003; 107: 992-5.

35. Wittstock A., Burkert M., Zidek W. et al. N-acetylcysteine improves arterial vascular reactivity in patients with chronic kidney disease. Nephron Clin Pract 2009; 112: 184-9.

36. Tesauro M., Schinzari F., Rovella V. et al. Ghrelin restores the endothelin 1/nitric oxide balance in patients with obesity-related metabolic syndrome. Hypertension 2009; 54: 995-1000.

37. Yasmin, McEniery C., Wallace S. et al. C-reactive protein is associated with arterial stiffness in apparently healthy individuals. Arterioscler Thromb Vasc Biol 2004; 24: 969-74.

38. Joly L., Djaballah W., Koehl G. et al. Aortic inflammation, as assessed by hybrid FDGPET/CT imaging, is associated with enhanced aortic stiffness in addition to concurrent calcification. Eur J Nucl Med Mol Imaging 2009; 36: 979-85.

39. Choi H., Hernan M., Seeger J. et al. Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 2002; 359: 1173-7.

40. Aikawa E., Aikawa M., Libby P. et al. Arterial and aortic valve calcification abolished by elastolytic cathepsin S deficiency in chronic renal disease. Circulation 2009; 119: 1785-94.

41. Kranzhofer R., Schmidt J., Pfeiffer C. et al. Angiotensin induces inflammatory activation of human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 1999; 19: 1623-9.

42. Takagishi T., Murahashi N., Azagami S. et al. Effect of angiotensin II and thromboxane A2 on the production of matrix metalloproteinase by human aortic smooth muscle cells. Biochem Mol Biol Int 1995;35: 265-73.

43. Guerin A., Blacher J., Pannier B. et al. Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure. Circulation 2001; 103: 987-92.

44. Blacher J., Amah G., Girerd X. et al. Association between increased plasma levels of aldosterone and decreased systemic arterial compliance in subjects with essential hypertension. Am J Hypertens 1997;10: 1326-34.

45. Lacolley P., Labat C., Pujol A. et al. Increased carotid wall elastic modulus and fibronectin in aldosteronesalt-treated rats: effects of eplerenone. Circulation 2002; 106: 2848-53.

46. Ullian M., Schelling J., Linas S. Aldosterone enhances angiotensin II receptor binding and inositol phosphate responses. Hypertension 1992; 20: 67-73.

47. Greene E., Kren S., Hostetter T. Role of aldosterone in the remnant kidney model in the rat. J Clin Invest 1996; 98: 1063-68.

48. Edwards N., Steeds R., Stewart P. et al. Effect of spironolactone on left ventricular mass and aortic stiffness in early-stage chronic kidney disease. A randomized controlled trial. J Am Coll Cardiol 2009; 54: 505-12.

49. Balamuthusamy S., Srinivasan L., Verma M. et al. Renin angiotensin system blockade and cardiovascular outcomes in patients with chronic kidney disease and proteinuria: a meta-analysis. Am Heart J 2008; 155: 791-805.

50. Safar M., Thuilliez C., Richard V. et al. Pressure-independent contribution of sodium to large artery structure and function in hypertension. Cardiovasc Res 2000; 46: 269-76.

51. Gates P., Tanaka H., Hiatt W. et al. Dietary sodium restriction rapidly improves large elastic artery compliance in older adults with systolic hypertension. Hypertension 2004; 44: 35-41.

52. Ferro C., Chue C., Steeds R. et al. Is lowering phosphate exposure the key to preventing arterial stiffening with age? Heart 2009; 95: 1770-2.

53. Toussaint N., Lau K., Strauss B. et al. Associations between vascular calcification, arterial stiffness and bone mineral density in chronic kidney disease. Nephrol Dial Transplant 2008; 23: 586-93.

54. London G., Guerin A., Marchais S. et al. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 2003; 18: 1731-40.

55. Jono S., McKee M., Murry C. et al. Phosphate regulation of vascular smooth muscle cell calcification. Circ Res 2000; 87: 10-17.

56. Jono S., Ikari Y., Vermeer C. et al. Matrix Gla protein is associated with coronary artery calcification as assessed by electron-beam computed tomography. Thromb Haemost 2004; 91: 790-4.

57. Ketteler M., Bongartz P., Westenfeld R. et al. Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study. Lancet 2003; 361: 827-33.

58. Rostand S., Drueke T. Parathyroid hormone, vitamin D, and cardiovascular disease in chronic renal failure. Kidney Int 1999; 56: 383-92.

59. Amann K., Tornig J., Kugel B. et al. Hyperphosphatemia aggravates cardiac fibrosis and microvascular disease in experimental uremia. Kidney Int 2003; 63: 1296-301.

For citation:

Kobalava J.D., Kotovskaya Yu.V., Villevalde S.V., Soloveva A.E., Amirbegishvili I.M. ARTERIAL STIFFNESS AND CHRONIC KIDNEY DISEASE: CAUSES AND CONSEQUENCES. Rational Pharmacotherapy in Cardiology. 2014;10(1):83-91. (In Russ.)

Views: 871

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)