Cardiovascular Disease in Chronic Kidney Disease: Pathophysiological Insights and Therapeutic Options

Abstract

Patients with chronic kidney disease (CKD) exhibit an elevated cardiovascular risk manifesting as coronary artery disease, heart failure, arrhythmias, and sudden cardiac death. Although the incidence and prevalence of cardiovascular events is already significantly higher in patients with early CKD stages (CKD stages 1-3) compared with the general population, patients with advanced CKD stages (CKD stages 4-5) exhibit a markedly elevated risk. Cardiovascular rather than end-stage kidney disease (CKD stage 5) is the leading cause of death in this high-risk population. CKD causes a systemic, chronic proinflammatory state contributing to vascular and myocardial remodeling processes resulting in atherosclerotic lesions, vascular calcification, and vascular senescence as well as myocardial fibrosis and calcification of cardiac valves. In this respect, CKD mimics an accelerated aging of the cardiovascular system. This overview article summarizes the current understanding and clinical consequences of cardiovascular disease in CKD.

Keywords: arrhythmias; cardiovascular disease; chronic kidney disease; clinical aspects; death; heart failure; sudden cardiac.

Figure 1.

Cardiovascular mortality in the general population and in patients with end-stage kidney disease. In 25- to 34-year-old patients with end-stage kidney disease, annual mortality is increased 500- to 1000-fold and corresponds to that of the ≈85-year-old general population. Adapted from Foley et al.

Figure 2.

Interaction of cardiovascular disease (CVD) and chronic kidney disease (CKD). Various mediators and mechanisms in vascular disease, heart failure, and CKD contribute to the progression of CVD and influence the prognosis of patients. PTM indicates post-translational modification.

Figure 3.

Classification and prognosis of chronic kidney disease (CKD) from 2012 KDIGO (Kidney Disease Improving Global Outcomes) guidelines. GFR indicates glomerular filtration rate. Adapted from the Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group.

Figure 4.

Annual incidence rates of end-stage kidney disease in different countries. Adapted from Jha et al.

Figure 5.

Independent association of kidney function with cardiovascular mortality. ACR indicates albumin-to-creatinine ratio; CKD, chronic kidney disease; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; and HR, hazard ratio. Adapted and modified from Gansevoort et al.

Figure 6.

Independent association of kidney function with cardiovascular mortality. ACR, albumin-to-creatinine ratio; and eGFR, estimated glomerular filtration rate. Adapted and modified from Gansevoort et al.

Figure 7.

Cause-specific mortality according to varying levels of kidney dysfunction. For the 3 categories of kidney dysfunction, cause-specific mortality is depicted. Sudden cardiac death was the major cause of death in patients with end-stage renal disease (ESRD) on dialysis (50.0% vs 10.1% [glomerular filtration rate {GFR} <60 mL/min] vs 10.3% [GFR ≥60 mL/min], χ² P=0.010). Number at the top of each bar is the mortality rate; number within the bar is the n per group. The unknown category was reserved for those patients whose cause of death could not be determined. Adapted from Cheema et al.