Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2006, vol. 15, nr 2, March-April, p. 227–232

Publication type: editorial article

Language: English

Early Development and Rapid Progression of Atherosclerosis in Patients with Chronic Kidney Disease

Wczesny rozwój i szybka progresja miażdżycy u pacjentów z przewlekłą chorobą nerek

Stanisław Czekalski1,, Andrzej Oko1,, Krzysztof Pawlaczyk1,

1 Department of Nephrology, Transplantology and Internal Diseases, University of Medical Sciences, Poznań, Poland


Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease, due mostly to premature development and accelerated course of atherosclerosis. Apart form traditional risk factors influencing the development of atherosclerosis in general population, the role of the factors associated with endothelial damage, the oxidative stress−altered lipoprotein structure and function and chronic inflammation was recently characterized. It was suggested that activation of local renin−angiotensin system, increased oxidative stress and production of proinflammatory cytokines like interleukin−6 (Il−6) and tumor necrosis factor−α (TNF−α) are probable candidates to play a key role in early stages of CKD. Persistent microalbuminuria and proteinuria are independent risk factors for progression of both renal injury and vascular disease. As kidney function impairment progresses in the course of CKD, the prevalence and magnitude of several non−traditional risk factors for atherosclerosis, such as oxidative stress, endothelial dysfunction, chronic inflammation, accumulation of advanced glycation end−products and other toxic metabolites and vascular calcification increase. In patients with renal failure low serum levels of cholesterol, homocysteine, low blood pressure and malnutrition are associated with increased cardiovascular morbidity and mortality and it was suggested that development of the malnutrition, inflammation, atherosclerosis (MIA) syndrome is involved in the “reverse epidemiology” of cardiovascular complications in patients with end−stage renal disease.

Key words

chronic kidney disease, atherosclerosis, oxidative stress, inflammation, cardiovascular disease

References (31)

  1. K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative. Am J Kidney Dis 2002, 39, suppl 2, S1–S266.
  2. Levey AS, Beto JA, Coronado BE, Eknoyan G, Foley RN, Kasiske BL, Klag MJ, Mailloux LU, Manske CL, Meyer KB, Parfrey PS, Pfeffer MA, Wenger NK, Wilson PW, Wright JT Jr: Controlling the epidemic of cardiovascular disease in chronic renal disease: what do we know? What do we need to learn? Where do we go from here? National Kidney Foundation Task Force on Cardiovascular Disease. Am J Kidney Dis 1998, 32, 853–906.
  3. Levey AS: Controllong the epidemic of cardiovascular disease in chronic renal disease: Where do we start? Am J Kidney Dis 1998, 32, suppl. 3, S5–S13.
  4. Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, McCullough PA, Kasiske BL, Kelepouris E, Klag MJ, Parfrey P, Pfeffer M, Raij L, Spinosa DJ, Wilson PW: American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention: Kidney disease as a risk factor for development of cardiovascular disease. A statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology and Epidemiology and Prevention. Circulation 2003, 108, 2154–2169.
  5. Kaysen GA, Eiserich JP: The role of oxidative stress−altered lipoprotein structure and function and microinflammation on cardiovascular risk in patients with minor renal dysfunction. J Am Soc Nephrol 2004, 15, 538–548.
  6. Jager A, van Hinsbergh VW, Kostense PJ, Emeis JJ, Nijpels G, Dekker JM, Heine RJ, Bouter LM, Stehouwer CD: Increased levels of soluble vascular cell adhesion molecule 1 are associated with risk of cardiovascular mortality in type 2 diabetes: the Hoorn study. Diabetes 2000, 49, 485–491.
  7. Hwang SJ, Ballantyne CM, Sharrett AR, Smith LC, Davis CE, Gotto AM Jr, Boerwinkle E: Circulating adhesion molecules VCAM−1, ICAM−1, and E−selectin in carotid atherosclerosis and incident coronary heart disease cases: The Atherosclerosis Risk In Communities (ARIC) study. Circulation 1997, 96, 4219–4225.
  8. Van Lenten BJ, Hama SY, de Beer FC, Stafforini DM, McIntyre TM, Prescott SM, La Du BN, Fogelman AM, Navab M: Antiinflammatory HDL becomes pro−inflammatory during the acute−phase response. Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures. J Clin Invest 1995, 96, 2758–2767.
  9. Artl A, Marsche G, Lestavel S, SattlerW, Malle E: Role of serum amyloid A during metabolism of acute−phase HDL by macrophages. Arterioscler Thomb Vasc Biol 2000, 20, 763–772.
  10. Hostetter TH, Olson JL, Rennke HG, Venkatachalam MA, Brenner BM: Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. J Am Soc Nephrol 2001, 12, 1315–1325.
  11. Luchtefeld M, Drexler H, Schieffer B: 5−Lipoxygenase is involved in the angiotensin II−induced NAD(P)H−oxidase activation. Biochem Biophys Res Commun 2003, 308, 668–672.
  12. Al Aly Z, Edwards JC: Vascular biology in uremia: insights into novel mechanisms of vascular injury. Adv Chron Kidney Dis 2004, 11, 310–318.
  13. Pigott R, Dillon LP, Hemingway IH, Gearing AJ: Soluble forms of E−selectin, ICAM−1 and VCAM−1 are present in the supernatants of cytokine activated cultured endothelial cells. Biochem Biophys Res Commun 1992, 187, 584–589.
  14. Ross R: The pathogenesis of atheroscelerosis: a prospective from the 1990s. Nature 1993, 362, 801–809.
  15. Albelda SM, Smith CW, Ward PA: Adhesion molecules and inflammatory injury. FASEB J 1994, 8, 504–512.
  16. Garg JP, Bakris GL: Microalbuminuria: marker of vascular dysfunction, risk factor for cardiovascular disease. Vase Med 2002, 7, 35–43.
  17. Keane WF: Proteinuria: Its clinical importance and role in progressive renal disease. Am J Kidney Dis 2000, 35, Suppl. S97–S105.
  18. Pecoits−Filho R, Heimburger O, Barany P, Suliman M, Fehrman−Ekholm I, Lindholm B, Stenvinkel P: Associations between circulating inflammatory markers and residual renal function in CRF patients. Am J Kidney Dis 2003, 41, 1212–1218.
  19. Shlipak MG, Fried LF, Crump C, Bleyer AJ, Manolio TA, Tracy RP, Furberg CD, Psaty BM: Elevations of inflammatory and procoagulant biomarkers in elderly persons with renal insufficiency. Circulation 2003, 107, 87–92.
  20. Fried LF, Shlipak MG, Crump C, Bleyer AJ, Gottdiener JS, Kronmal RA, Kuller LH, Newman AB: Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals. J Am Coll Cardiol 2003, 41, 1364–1372.
  21. Mann JF, Gerstein HC, Dulau−Florea I, Lonn E: Cardiovascular risk in patients with mild renal insufficiency. Kidney Int. 2003, Suppl. 84, S192–S196.
  22. Yao Q, Pecoits−Filho R, Lindholm B, Stenvinkel P: Traditional and non−traditional risk factors as contributors to atherosclerotic cardiovascular disease in end−stage renal disease. Scand J Urol Nephrol 2004, 38, 405–416.
  23. Stenvinkel P, Alvestrand A: Inflammation in end−stage renal disease: sources, consequences, and therapy. Semin Dial 2002, 15, 329–337.
  24. Stenvinkel P, Heimburger O, Jogestrand T: Elevated interleukin−6 predict progressive carotid atherosclerosis in dialysis patients: Association to Chlamydia pneumoniae seropositivity. Am J Kidney Dis 2002, 39, 274–282.
  25. Zoccali C, Benedetto FA, Maas R, Mallamaci F, Tripepi G, Malatino LS, Boger R: CREED Investigators: Asymmetric dimethyl−arginine, C−reactive protein, and carotid intima−media thickness in end−stage renal disease. J Am Soc Nephrol 2002, 13, 490–496.
  26. Zoccali C, Mallamaci F, Maas R, Benedetto FA, Tripepi G, Malatino LS, Cataliotti A, Bellanuova I, Boger R: CREED Investigators: Left ventricular hypertrophy, cardiac remodeling and asymmetric dimethyl−arginine (ADMA) in hemodialysis patients. Kidney Int 2002, 63, 339–345.
  27. Ketteler M, Bongartz P, Westenfeld R, Wildberger JE, Mahnken AH, Bohm R, Metzger T, Wanner C, Jahnen−Dechent W, Floege J: Association of low fetuin A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross−sectional study. Lancet 2003, 361, 827–833.
  28. Nitta K, Akiba T, Uchida K, Kawashima A, Yumura W, Kabaya T, Nihei H: The progression of vascular calcification and serum osteoprotegerin levels in patients on long−term hemodialysis. Am J Kidney Dis 2003, 42, 303–309.
  29. Schwarz U, Buzello M, Ritz E, Stein G, Raabe G, Wiest G, Mall G, Amann K: Morphology of coronary atherosclerotic lesions in patients with end−stage renal failure. Nephrol Dial Transplant 2000, 15, 218–223.
  30. Cheung AK, Sarnak MJ, Yan G, Dwyer JT, Heyka RJ, Rocco MV, Teehan BP, Levey AS: Atherosclerotic cardiovascular disease risks in chronic hemodialysis patients. Kidney Int 2000, 58, 353–362.
  31. Stenvinkel P, Heimburger O, Lindholm B, Kaysen GA, Bergstrom J: Are there two types of malnutrition in chronic renal failure? Evidence for relationships between malnutrition, inflammation and atherosclerosis (MIA syndrome). Nephrol Dial Transplant 2000, 15, 953–960.