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Atherosclerosis in CKD: differences from the general population

Abstract

The prevalence of cardiovascular morbidity and mortality is higher in patients with chronic kidney disease (CKD)—especially those with end-stage renal disease—than in the general population. The contribution of atherosclerosis to cardiovascular disease in patients with CKD remains unclear. Researchers in the 1970s proposed that atherosclerosis was the main cause of cardiovascular disease in patients with CKD and that its progression, based on observations of patients on long-term dialysis, was accelerated by the uremic state. Subsequent reports, however, favor the involvement of other mechanisms, such as arteriosclerosis (characterized by vascular stiffening), vascular calcification, 'myocyte/capillary mismatch', congestive cardiomyopathy, and sudden cardiac death. Imaging and morphological studies have contributed to our understanding of the pathogenesis and progression of cardiovascular disease associated with CKD. Based on clinical and experimental findings, we hypothesize the following: the initial cardiovascular abnormalities in the CKD setting include arteriosclerosis, left ventricular diastolic dysfunction, and left ventricular hypertrophy, abnormalities which, in adult patients, are often accompanied by atherosclerosis. The prevalence of atherosclerosis increases with age and is aggravated, but not specifically induced, by CKD. The cardiovascular events associated with atherosclerosis are more often fatal in patients with CKD than in individuals without CKD.

Key Points

  • The first cardiovascular changes observed in patients with chronic kidney disease (CKD) are arteriosclerosis (characterized by arterial stiffening and loss of cushioning function), altered left ventricular diastolic function and left ventricular hypertrophy

  • Atherosclerosis (characterized by intimal thickening and loss of conduit function) often occurs in parallel with initial cardiovascular changes (especially in elderly patients with CKD) and is probably not induced, but is aggravated by CKD

  • The severity of atherosclerosis in patients with CKD could be affected by changes in plaque composition (that is, by qualitative differences) rather than by atheromatous plaque number or volume

  • Intimal calcification is high in patients with CKD; although medial calcification is associated with arteriosclerosis, it is probably a secondary event in the late stages of CKD

  • The role of uremia-specific factors in cardiovascular disease, as opposed to the classical risk factors (age, hypertension, diabetes, and smoking) requires further investigation

  • Atherosclerosis clearly contributes to the high cardiovascular mortality rate of patients with CKD but is probably not one of the main causes of death

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Figure 1: Age-standardized rates of death from cardiovascular events according to estimated GFR in ambulatory adults from the USA.
Figure 2: Pathogenesis of ischemic heart disease.
Figure 3: Coronary atherosclerosis in patients with various degrees of chronic kidney disease (CKD).
Figure 4: Proportion of atherosclerotic lesion types of coronary arteries as a function of CKD stage.
Figure 5: Hypothetical role of mild to moderate chronic kidney disease (CKD; uremic toxicity) in the occurrence of cardiovascular dysfunction.

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Acknowledgements

The authors wish to thank S. Rostand, from the University of Alabama at Birmingham, AL, USA, for helpful discussion and suggestions for this manuscript.

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T. B. Drüeke and Z. A. Massy contributed equally to researching data for the article, substantial discussion of the content of the article and reviewing/editing the manuscript before submission. T. B. Drüeke wrote the initial draft of the article.

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Correspondence to Tilman B. Drüeke.

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Drüeke, T., Massy, Z. Atherosclerosis in CKD: differences from the general population. Nat Rev Nephrol 6, 723–735 (2010). https://doi.org/10.1038/nrneph.2010.143

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