Specificities of the treatment for vascular system diseases in patients with a chronic renal disease

Authors: Petr Táborský
Published in: AtheroRev 2019; 4(3): 138-144


Chronic kidney disease is a significant risk factor for cardiovascular complications. The main cause of mortality in kidney failure is a complex vascular disease manifested as athero- and arteriosclerosis. Vascular involvement starts very early in the course of kidney disease. Besides classical risk factors the specific, uremia-related factors are in action. Most important of them is the bone and mineral disorder (CKD-MBD). Vascular wall injury is initiated by hyperphosphatemia, later on the vascular calcifications are formed. Deficit of Klotho and high concentration of phosphatonin FGF23 contribute to accelerated aging of vessels. First clinical sign of this disorder is vascular stiffness which can be quantified by pulse wave velocity measurement. CKD-MBD treatment consists of hyperphosphatemia prevention by diet, phosphate binders administration, secondary hyperparathyroidism management and phosphate removal by dialysis.


arteriosclerosis – bone and mineral disorder – chronic kidney disease – FGF23 – Klotho – Parathyroid hormone – phosphorus

  1. Schieppati A, Remuzzi G. Chronic renal disease as a public health problem: Epidemiology, social and economic implications. Kidney Int Suppl 2005; (98): S7-S10. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1523–1755.2005.09801.x>.
  2. Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998; 32(5 Suppl 3): S112-S119.
  3. Foley RN. Murray AM, Li S et al. Chronic Kidney Disease and the Risk for Cardiovascular Disease, Renal Replacement, and Death in the United States Medicare Population, 1998 to 1999. J Am Soc Nephrol. 2005; 16(2): 489–495. Dostupné z DOI: <http://dx.doi.org/10.1681/ASN.2004030203>.
  4. Go AS, Chertow GM, Fan D et al. Chronic Kidney Disease and the Risks of Death, Cardiovascular Events, and Hospitalization. N Engl J Med 2004; 351(13): 1296–1305. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa041031>.
  5. United States Renal Data System. 2018 USRDS annual data report: Epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2018.
  6. Bright R. Cases and observations illustrative of renal disease accompanied with the secretion of albuminous urine. Guy’s Hospital Trans 1836; 1: 338–379
  7. Lindner A, Charra B, Sherrard DJ et al. Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med 1974; 290(13): 697–701. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJM197403282901301>.
  8. Kalantar-Zadeh K, Block G, Humphreys MH et al. Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients. Kidney Int 2003; 63(3):793–808. Dostupné z DOI: <http://dx.doi.org/10.1046/j.1523–1755.2003.00803.x>.
  9. Cozzolino M, Mangano M, Stucchi A et al. Cardiovascular disease in dialysis patients. Nephrol Dial Transplant 2018; 33(Suppl 3): iii28-iii34. Dostupné z DOI: <http://dx.doi.org/10.1093/ndt/gfy174>.
  10. Besarab A, Bolton WK, Browne JK et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 1998; 339(9): 584–590. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJM199808273390903>.
  11. Eknoyan G, Beck GJ, Cheung AK et al. Hemodialysis (HEMO) Study Group. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med 2002; 347(25): 2010–1019. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa021583>.
  12. Paniagua R, Amato D, Vonesh E et al. Effects of increased peritoneal clearances on mortality rates in peritoneal dialysis: ADEMEX, a prospective, randomized, controlled trial. J Am Soc Nephrol 2002; 13(5): 1307–1320.
  13. KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral and Bone Disorder (CKD–MBD). Kidney Int Suppl 2009; 76(113): S1–130. Dostupné z DOI: <http://dx.doi.org/10.1038/ki.2009.188>.
  14. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease – Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl (2011) 2017; 7: 1–59. Dostupné z DOI: <http://dx.doi.org/10.1016/j.kisu.2017.04.00>.
  15. John GB, Cheng CY, Kuro-o M. Role of Klotho in aging, phosphate metabolism and CKD. Am J Kidney Dis 2011; 58(1): 127–134. Dostupné z DOI: <http://dx.doi.org/10.1053/j.ajkd.2010.12.027>.
  16. Block GA, Hulbert-Shearon TE, Levin NW et al. Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J Kidney Dis 1998; 31(4): 607–617. Dostupné z DOI: <http://dx.doi.org/10.1053/ajkd.1998.v31.pm9531176>.
  17. Goodman WG, Goldin J, Kuizon BD et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000; 342(20): 1478–1483. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJM200005183422003>.
  18. Gross P, Six I, Kamel S et al. Vascular toxicity of phosphate in chronic kidney disease: beyond vascular calcification. Circ J 2014; 78(10): 2339–2346. Dostupné z DOI: <http://dx.doi.org/10.1253/circj.cj-14–0735>.
  19. London GM, Marchais SJ, Guérin AP et al. Arteriosclerosis, vascular calcifications and cardiovascular disease in uremia. Curr Opin Nephrol Hypertens 2005; 14(6): 525–531.
  20. Zoccali C, London G. Con: vascular calcification is a surrogate marker, but not the cause of ongoing vascular disease, and it is not a treatment target in chronic kidney disease. Nephrol Dial Transplant 2015; 30(3): 352–357. Dostupné z DOI: <http://dx.doi.org/10.1093/ndt/gfv021>.
  21. Zanoli L, Lentini P, Briet M et al. Arterial Stiffness in the Heart Disease of CKD. J Am Soc Nephrol 2019; 30(6): 918–928. Dostupné z DOI: <http://dx.doi.org/10.1681/ASN.2019020117>.
  22. Ferreira JP, Girerd N, Pannier B et al. High Pulse-Wave Velocity Defines a Very High Cardiovascular Risk Cohort of Dialysis Patients under Age 60. Am J Nephrol 2017; 45(1): 72–81. Dostupné z DOI: <http://dx.doi.org/10.1159/000453338>.
  23. Chirinos JA, Segers P, Hughes T et al. Large-Artery Stiffness in Health and Disease: JACC State-of-the-Art Review. J Am Coll Cardiol 2019; 74(9): 1237–1263. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2019.07.012>.
  24. Kuro-O M. The FGF23 and Klotho system beyond mineral metabolism. Clin Exp Nephrol. 2017; 21(Suppl 1): 64–69. Dostupné z DOI: <http://dx.doi.org/10.1007/s10157–016–1357–6>.
  25. Ferrari SL, Bonjour JP, Rizzoli R. Fibroblast growth factor-23 relationship to dietary phosphate and renal phosphate handling in healthy young men. J Clin Endocrinol Metab 2005; 90(3): 1519–1524. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2004–1039>.
  26. Scialla JJ, Xie H, Rahman M et al. Fibroblast growth factor-23 and cardiovascular events in CKD. J Am Soc Nephrol 2014; 25(2):349–360.. Dostupné z DOI: <http://dx.doi.org/10.1681/ASN.2013050465>.
  27. Leifheit-Nestler M, Haffner D. Paracrine Effects of FGF23 on the Heart. Front Endocrinol (Lausanne). 2018; 9: 278. Dostupné z DOI: <http://dx.doi.org/10.3389/fendo.2018.00278>.
  28. Wang TJ, Pencina MJ, Booth SL et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008; 117(4): 503–511. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.107.706127>.
  29. de Borst MH, Vervloet MG, ter Wee PM et al. Cross talk between the renin-angiotensin-aldosterone system and vitamin D-FGF-23-klotho in chronic kidney disease. J Am Soc Nephrol. 2011; 22(9): 1603–1609. Dostupné z DOI: <http://dx.doi.org/10.1681/ASN.2010121251>.
  30. Kuro-o M. A potential link between phosphate and aging-Lessons from Klotho-deficient mice. Mech Ageing Dev 2010; 131(4): 270–275. Dostupné z DOI: <http://dx.doi.org/10.1016/j.mad.2010.02.008>.
  31. Drew DA, Katz R, Kritchevsky S et al. Association between Soluble Klotho and Change in Kidney Function: The Health Aging and Body Composition Study. J Am Soc Nephrol 2017; 28(6): 1859–1866. Dostupné z DOI: <http://dx.doi.org/10.1681/ASN.2016080828>.
  32. Dhingra R, Sullivan LM, Fox CS et al. Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Arch Intern Med 2007; 167(9): 879–885. Dostupné z DOI: <http://dx.doi.org/10.1001/archinte.167.9.879>.
  33. Tonelli M, Sacks F, Pfeffer M et al. Relation between serum phosphate level and cardiovascular event rate in people with coronary disease. Circulation 2005; 112(17): 2627–2633. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.105.553198>.
  34. Mazzaferro S, Pasquali M. Vitamin D: a dynamic molecule. How relevant might the dynamism for a vitamin be? Nephrol Dial Transplant 2016; 31(1): 23–30. Dostupné z DOI: <http://dx.doi.org/10.1093/ndt/gfv340>.
  35. Millar SA, Anderson SI, O‘Sullivan SE. Osteokines and the vasculature: a review of the in vitro effects of osteocalcin, fibroblast growth factor-23 and lipocalin-2. Peer J 2019; 7: e7139. Dostupné z DOI: <http://dx.doi.org/10.7717/peerj.7139>.
  36. Mera P, Ferron M, Mosialou I. Regulation of Energy Metabolism by Bone-Derived Hormones. Cold Spring Harb Perspect Med 2018; 8(6). pii: a031666. Dostupné z DOI: <http://dx.doi.org/10.1101/cshperspect.a031666>.
  37. Barreto FC, Barreto DV, Massy ZA et al. Strategies for Phosphate Control in Patients With CKD. Kidney Int Rep 2019; 4(8): 1043–1056. Dostupné z DOI: <http://dx.doi.org/10.1016/j.ekir.2019.06.002>.
  38. Francisco RC, Aloha M, Ramón PS. Effects of high-efficiency postdilution online hemodiafiltration and high-flux hemodialysis on serum phosphorus and cardiac structure and function in patients with end-stage renal disease. Int Urol Nephrol 2013; 45(5): 1373–1378. Dostupné z DOI: <http://dx.doi.org/10.1007/s11255–012–0324–8>.
  39. Miao LY, Zhu B, He XZ et al. Effects of three blood purification methods on serum fibroblast growth factor-23 clearance in patients with hyperphosphatemia undergoing maintenance hemodialysis. Exp Ther Med 2014; 7(4): 947–952. Dostupné z DOI: <http://dx.doi.org/10.3892/etm.2014.1543>.
  40. Dulai R, Perry M, Twycross-Lewis R et al. The effect of tumor necrosis factor-α antagonists on arterial stiffness in rheumatoid arthritis: a literature review. Semin Arthritis Rheum. 2012; 42(1): 1–8. Dostupné z DOI: <http://dx.doi.org/10.1016/j.semarthrit.2012.02.002>.
  41. Bellien J, Fréguin-Bouilland C, Joannidès R et al. High-efficiency on-line haemodiafiltration improves conduit artery endothelial function compared with high-flux haemodialysis in end-stage renal disease patients. Nephrol Dial Transplant 2014; 29(2): 414–422. Dostupné z DOI: <http://dx.doi.org/10.1093/ndt/gft448>.
  42. Jansz TT, Verhaar MC, London GM et al. Is progression of coronary artery calcification influenced by modality of renal replacement therapy? A systematic review. Clin Kidney J 2018; 11(3): 353–361. Dostupné z DOI: <http://dx.doi.org/10.1093/ckj/sfx124>.
Angiology Diabetology Internal medicine Cardiology General practitioner for adults

Article was published in

Athero Review

Issue 3

2019 Issue 3

Most read in this issue
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account