Large Artery Remodeling and Chronic Kidney Disease

  • Marie Briet
  • Michel Delahousse
  • Gérard London
  • Stéphane LaurentEmail author
  • Pierre Boutouyrie


In recent years, many studies emphasized the role of arterial remodeling in the development of cardiovascular diseases, and it was shown that stiffening of arteries is associated with increased cardiovascular mortality and morbidity. Moreover, arterial stiffening is linked to decreased glomerular filtration rate, and is predictive of kidney-disease progression and the patient’s cardiovascular outcome. Early vascular aging and arterial stiffening are observed with progression of chronic kidney disease (CKD) and in end-stage renal disease (ESRD). This accelerated aging is associated with outward remodeling of large vessels, characterized by increased arterial radius not totally compensated for by artery wall hypertrophy. The mechanisms involved in large artery remodelling associated with CKD are complex including arterial calcification, inflammation, oxidative stress in association with mineral and bone metabolism disorders. Arterial stiffening in CKD and ESRD patients is of multifactorial origin with extensive arterial calcifications representing a major covariate. With aging, arterial stiffening is more pronounced in the aorta than peripheral conduit arteries, leading to the disappearance or inversion of the arterial stiffness gradient and less protection of the microcirculation from high-pressure transmission. Various non-pharmacological or pharmacological interventions can modestly slow the progression of arterial stiffness, but arterial stiffness is, in part, pressure-dependent and treatments able to stop the process mainly include antihypertensive drugs.


Arterial stiffness Cardiovascular events Epidemiology Surrogate end point 



  1. 1.
    Stevens PE, Levin A, Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013;158:825–30.PubMedCrossRefGoogle Scholar
  2. 2.
    Castro AF, Coresh J. CKD surveillance using laboratory data from the population-based National Health and Nutrition Examination Survey (NHANES). Am J Kid Dis. 2009;53:S46–55.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Gansevoort RT, et al. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet. 2013;382:339–52.PubMedCrossRefGoogle Scholar
  4. 4.
    Murphy SW, Foley RN, Parfrey PS. Screening and treatment for cardiovascular disease in patients with chronic renal disease. Am J Kidney Dis. 1998;32:S184–99.PubMedCrossRefGoogle Scholar
  5. 5.
    Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis. 1998;32:S112–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–305.PubMedCrossRefGoogle Scholar
  7. 7.
    Couser WG, Remuzzi G, Mendis S, Tonelli M. The contribution of chronic kidney disease to the global burden of major noncommunicable diseases. Kidney Int. 2011;80(12):1258–70.Google Scholar
  8. 8.
    Keith DS, Nichols GA, Gullion CM, Brown JB, Smith DH. Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med. 2004;164:659–63.PubMedCrossRefGoogle Scholar
  9. 9.
    Kottgen A, et al. Reduced kidney function as a risk factor for incident heart failure: the atherosclerosis risk in communities (ARIC) study. J Am Soc Nephrol. 2007;18:1307–15.PubMedCrossRefGoogle Scholar
  10. 10.
    Abramson JL, Jurkovitz CT, Vaccarino V, Weintraub WS, McClellan W. Chronic kidney disease, anemia, and incident stroke in a middle-aged, community-based population: the ARIC Study. Kidney Int. 2003;64:610–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Wattanakit K, et al. Kidney function and risk of peripheral arterial disease: results from the Atherosclerosis Risk in Communities (ARIC) Study. J Am Soc Nephrol. 2007;18:629–36.PubMedCrossRefGoogle Scholar
  12. 12.
    Jurkovitz CT, Abramson JL, Vaccarino LV, Weintraub WS, McClellan WM. Association of high serum creatinine and anemia increases the risk of coronary events: results from the prospective community-based atherosclerosis risk in communities (ARIC) study. J Am Soc Nephrol. 2003;14:2919–25.PubMedCrossRefGoogle Scholar
  13. 13.
    Alonso A, et al. Chronic kidney disease is associated with the incidence of atrial fibrillation: the Atherosclerosis Risk in Communities (ARIC) study. Circulation. 2011;123:2946–53.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Weiner DE, et al. The Framingham predictive instrument in chronic kidney disease. J Am Coll Cardiol. 2007;50:217–24.PubMedCrossRefGoogle Scholar
  15. 15.
    Schiffrin EL, Lipman ML, Mann JF. Chronic kidney disease: effects on the cardiovascular system. Circulation. 2007;116:85–97.PubMedCrossRefGoogle Scholar
  16. 16.
    Drueke TB, Massy ZA. Chronic kidney disease: medial or intimal calcification in CKD-does it matter? Nat Rev Nephrol. 2011;7:250–1.PubMedCrossRefGoogle Scholar
  17. 17.
    Toynbee J. On the intimate structure of the human kidney, and on the changes which its several component parts undergo in “Bright’s disease”. Med Chir Trans. 1846;29:303–26.PubMedCentralPubMedGoogle Scholar
  18. 18.
    London GM, et al. Aortic and large artery compliance in end-stage renal failure. Kidney Int. 1990;37:137–42.PubMedCrossRefGoogle Scholar
  19. 19.
    Briet M, Boutouyrie P, Laurent S, London GM. Arterial stiffness and pulse pressure in CKD and ESRD. Kidney Int. 2012;82:388–400.PubMedCrossRefGoogle Scholar
  20. 20.
    Wang MC, Tsai WC, Chen JY, Huang JJ. Stepwise increase in arterial stiffness corresponding with the stages of chronic kidney disease. Am J Kidney Dis. 2005;45:494–501.PubMedCrossRefGoogle Scholar
  21. 21.
    Briet M, et al. Arterial stiffness and enlargement in mild-to-moderate chronic kidney disease. Kidney Int. 2006;69:350–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Townsend RR, et al. Aortic PWV in chronic kidney disease: a CRIC ancillary study. Am J Hypertens. 2010;23:282–9.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Ford ML, Tomlinson LA, Chapman TP, Rajkumar C, Holt SG. Aortic stiffness is independently associated with rate of renal function decline in chronic kidney disease stages 3 and 4. Hypertension. 2010;55:1110–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Briet M, et al. Arterial remodeling associates with CKD progression. J Am Soc Nephrol. 2011;22:967–74.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Chen SC, et al. The longitudinal change of arterial stiffness in patients with chronic kidney disease. Am J Med Sci. 2012;343(2):109–13.Google Scholar
  26. 26.
    Bansal N, et al. A longitudinal study of left ventricular function and structure from CKD to ESRD: the CRIC study. Clin J Am Soc Nephrol. 2013;8:355–62.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Utescu MS, et al. Determinants of progression of aortic stiffness in hemodialysis patients: a prospective longitudinal study. Hypertension. 2013;62:154–60.PubMedCrossRefGoogle Scholar
  28. 28.
    Pannier B, Guerin AP, Marchais SJ, Safar ME, London GM. Stiffness of capacitive and conduit arteries: prognostic significance for end-stage renal disease patients. Hypertension. 2005;45:592–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Hayoz D, et al. Conduit artery compliance and distensibility are not necessarily reduced in hypertension. Hypertension. 1992;20:1–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Bussy C, Boutouyrie P, Lacolley P, Challande P, Laurent S. Intrinsic stiffness of the carotid arterial wall material in essential hypertensives. Hypertension. 2000;35:1049–54.PubMedCrossRefGoogle Scholar
  31. 31.
    van Guldener C, Lambert J, Janssen MJ, Donker AJ, Stehouwer CD. Endothelium-dependent vasodilatation and distensibility of large arteries in chronic haemodialysis patients. Nephrol Dial Trans. 1997;12 Suppl 2:14–8.Google Scholar
  32. 32.
    London GM, et al. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Trans. 2003;18:1731–40.CrossRefGoogle Scholar
  33. 33.
    Raggi P, et al. Association of pulse wave velocity with vascular and valvular calcification in hemodialysis patients. Kidney Int. 2007;71:802–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Sigrist MK, Taal MW, Bungay P, McIntyre CW. Progressive vascular calcification over 2 years is associated with arterial stiffening and increased mortality in patients with stages 4 and 5 chronic kidney disease. Clin J Am Soc Nephrol. 2007;2:1241–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Hruska KA, Mathew S, Saab G. Bone morphogenetic proteins in vascular calcification. Circ Res. 2005;97:105–14.Google Scholar
  36. 36.
    Mori K, et al. Association of serum fetuin-A with carotid arterial stiffness. Clin Endocrinol (Oxf). 2007;66:246–50.CrossRefGoogle Scholar
  37. 37.
    Gross ML, et al. Calcification of coronary intima and media: immunohistochemistry, backscatter imaging, and x-ray analysis in renal and nonrenal patients. Clin J Am Soc Nephrol. 2007;2:121–34.PubMedCrossRefGoogle Scholar
  38. 38.
    Hermans MM, et al. Albuminuria, but not estimated glomerular filtration rate, is associated with maladaptive arterial remodeling: the Hoorn Study. J Hypertens. 2008;26:791–7.PubMedCrossRefGoogle Scholar
  39. 39.
    London GM, et al. Cardiac and arterial interactions in end-stage renal disease. Kidney Int. 1996;50:600–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Luksha N, et al. Impaired resistance artery function in patients with end-stage renal disease. Clin Sci. 2011;120:525–36.PubMedCrossRefGoogle Scholar
  41. 41.
    Girerd X, et al. Remodeling of the radial artery in response to a chronic increase in shear stress. Hypertension. 1996;27:799–803.PubMedCrossRefGoogle Scholar
  42. 42.
    Mack WJ, et al. One-year reduction and longitudinal analysis of carotid intima-media thickness associated with colestipol/niacin therapy. Stroke. 1993;24:1779–83.PubMedCrossRefGoogle Scholar
  43. 43.
    Lorenz MW, et al. Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): a meta-analysis of individual participant data. Lancet. 2012;379:2053–62.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Bidani AK, Polichnowski AJ, Loutzenhiser R, Griffin KA. Renal microvascular dysfunction, hypertension and CKD progression. Curr Opin Nephrol Hypertens. 2013;22:1–9.PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Bidani AK, Griffin KA, Williamson G, Wang X, Loutzenhiser R. Protective importance of the myogenic response in the renal circulation. Hypertension. 2009;54:393–8.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Hashimoto J, Ito S. Central pulse pressure and aortic stiffness determine renal hemodynamics: pathophysiological implication for microalbuminuria in hypertension. Hypertension. 2011;58:839–46.PubMedCrossRefGoogle Scholar
  47. 47.
    Upadhyay A, et al. Arterial stiffness in mild-to-moderate CKD. J Am Soc Nephrol. 2009;20:2044–53.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Gosse P, Coulon P, Papaioannou G, Litalien J, Lemetayer P. Long-term decline in renal function is linked to initial pulse pressure in the essential hypertensive. J Hypertens. 2009;27:1303–8.PubMedCrossRefGoogle Scholar
  49. 49.
    Laurent S, Mousseaux E, Boutouyrie P. Arterial stiffness as an imaging biomarker: are all pathways equal? Hypertension. 2013;62:10–2.PubMedCrossRefGoogle Scholar
  50. 50.
    Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol. 2010;55:1318–27.PubMedCrossRefGoogle Scholar
  51. 51.
    Karras A, et al. Large artery stiffening and remodeling are independently associated with all-cause mortality and cardiovascular events in chronic kidney disease. Hypertension. 2012;60:1451–7.PubMedCrossRefGoogle Scholar
  52. 52.
    Blacher J, et al. Impact of aortic stiffness on survival in end-stage renal disease. Circulation. 1999;99:2434–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Guerin AP, et al. Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure. Circulation. 2001;103:987–92.PubMedCrossRefGoogle Scholar
  54. 54.
    Covic A, Goldsmith DJ, Gusbeth-Tatomir P, Buhaescu I, Covic M. Successful renal transplantation decreases aortic stiffness and increases vascular reactivity in dialysis patients. Transplantation. 2003;76:1573–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Zoungas S, et al. Arterial function after successful renal transplantation. Kidney Int. 2004;65:1882–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Bachelet-Rousseau C, et al. Evolution of arterial stiffness after kidney transplantation. Nephrol Dial Trans. 2011;26:3386–91.CrossRefGoogle Scholar
  57. 57.
    Delahousse M, et al. Aortic stiffness of kidney transplant recipients correlates with donor age. J Am Soc Nephrol. 2008;19:798–805.PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Verbeke F, Van Biesen W, Peeters P, Van Bortel LM, Vanholder RC. Arterial stiffness and wave reflections in renal transplant recipients. Nephrol Dial Trans. 2007;22:3021–7.CrossRefGoogle Scholar
  59. 59.
    Bahous SA, et al. Aortic pulse wave velocity in renal transplant patients. Kidney Int. 2004;66:1486–92.PubMedCrossRefGoogle Scholar
  60. 60.
    Opazo Saez A, Kos M, Witzke O, Kribben A, Nurnberger J. Effect of new-onset diabetes mellitus on arterial stiffness in renal transplantation. Trans Int. 2008;21:930–5.CrossRefGoogle Scholar
  61. 61.
    Van Laecke S, et al. The relation between hypomagnesaemia and vascular stiffness in renal transplant recipients. Nephrol Dial Trans. 2011;26:2362–9.CrossRefGoogle Scholar
  62. 62.
    Joannides R, et al. Comparative effects of sirolimus and cyclosporin on conduit arteries endothelial function in kidney recipients. Trans Int. 2010;23:1135–43.CrossRefGoogle Scholar
  63. 63.
    Joannides R, et al. Immunosuppressant regimen based on sirolimus decreases aortic stiffness in renal transplant recipients in comparison to cyclosporine. Am J Trans. 2011;11:2414–22.CrossRefGoogle Scholar
  64. 64.
    Verbeke F, et al. Aortic stiffness and central wave reflections predict outcome in renal transplant recipients. Hypertension. 2011;58:833–8.PubMedCrossRefGoogle Scholar
  65. 65.
    Briet M, Burns KD. Chronic kidney disease and vascular remodelling: molecular mechanisms and clinical implications. Clin Sci. 2012;123:399–416.PubMedCrossRefGoogle Scholar
  66. 66.
    Faqah A, Jafar TH. Control of blood pressure in chronic kidney disease: how low to go. Nephron Clin Pract. 2011;119:c324–31; discussion c331–22.PubMedCrossRefGoogle Scholar
  67. 67.
    Lehoux S, Tedgui A. Signal transduction of mechanical stresses in the vascular wall. Hypertension. 1998;32:338–45.PubMedCrossRefGoogle Scholar
  68. 68.
    Loufrani L, et al. Key role of alpha(1)beta(1)-integrin in the activation of PI3-kinase-Akt by flow (shear stress) in resistance arteries. Am J Physiol Heart Circ Physiol. 2008;294:H1906–13.PubMedCrossRefGoogle Scholar
  69. 69.
    Vaziri ND, Norris K. Lipid disorders and their relevance to outcomes in chronic kidney disease. Blood Purif. 2011;31:189–96.PubMedCrossRefGoogle Scholar
  70. 70.
    Preston E, Ellis MR, Kulinskaya E, Davies AH, Brown EA. Association between carotid artery intima-media thickness and cardiovascular risk factors in CKD. Am J Kidney Dis. 2005;46:856–62.PubMedCrossRefGoogle Scholar
  71. 71.
    Fellstrom BC, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009;360:1395–407.PubMedCrossRefGoogle Scholar
  72. 72.
    Chue CD, et al. Serum phosphate but not pulse wave velocity predicts decline in renal function in patients with early chronic kidney disease. Nephrol Dial Trans. 2011;26:2576–82.CrossRefGoogle Scholar
  73. 73.
    Kovesdy CP, Kuchmak O, Lu JL, Kalantar-Zadeh K. Outcomes associated with phosphorus binders in men with non-dialysis-dependent CKD. Am J Kidney Dis. 2010;56:842–51.PubMedCentralPubMedCrossRefGoogle Scholar
  74. 74.
    Scialla JJ, et al. Fibroblast growth factor-23 and cardiovascular events in CKD. J Am Soc Nephrol. 2014;25(2):349–60.Google Scholar
  75. 75.
    Desjardins L, et al. FGF23 is independently associated with vascular calcification but not bone mineral density in patients at various CKD stages. Osteoporos Int. 2012;23(7):2017–25.Google Scholar

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  • Marie Briet
    • 1
    • 2
  • Michel Delahousse
    • 3
  • Gérard London
    • 4
  • Stéphane Laurent
    • 5
    Email author
  • Pierre Boutouyrie
    • 5
  1. 1.Department of PharmacologyCentre Hospitalo-Universitaire d’Angers, Université d’AngersAngersFrance
  2. 2.Lady Davis Institute for Medical Research, McGill UniversityMontrealCanada
  3. 3.Department of Nephrology and TransplantationFoch HospitalSuresnesFrance
  4. 4.Department of NephrologyHopital ManhesFleury-MérogisFrance
  5. 5.Department of Pharmacology and Institut National de la Santé et de la Recherche Médicale U970(Eq7)-PARCCHôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris-DescartesParisFrance

Personalised recommendations