Why do young people with chronic kidney disease die early?

Abstract

Cardiovascular disease poses the greatest risk of premature death seen among patients with chronic kidney disease (CKD). Up to 50% of mortality risk in the dialysis population is attributable to cardiovascular disease and the largest relative excess mortality is observed in younger patients. In early CKD, occlusive thrombotic coronary disease is common, but those who survive to reach end-stage renal failure requiring dialysis are more prone to sudden death attributable mostly to sudden arrhythmic events and heart failure related to left ventricular hypertrophy, coronary vascular calcification and electrolyte disturbances. In this review, we discuss the basis of the interaction of traditional risk factors for cardiovascular disease with various pathological processes such as endothelial dysfunction, oxidative stress, low grade chronic inflammation, neurohormonal changes and vascular calcification and stiffness which account for the structural and functional cardiac changes that predispose to excess morbidity and mortality in young people with CKD.

Keywords: Cardiorenal syndrome; Cardiovascular mortality; Chronic kidney disease; Endothelial dysfunction; Vascular calcification and stiffness.

Figure 1

All-cause mortality and its relationship to worsening chronic kidney disease. After Go AS 2004[1].

Figure 2

Cardiovascular event rates according to chronic kidney disease stage. After Go AS 2004[1].

Figure 3

The physiological roles of nitric oxide on endothelial function.

Figure 4

Microalbuminuria as a risk factor for death in type 2 diabetes. Reproduced from Schmitz et al[49], 1988.

Figure 5

Maturation of high-density lipoprotein and the protective effect of apoA-I mimetic peptide 4F. (Apo)A-I: Apolipoprotein A-I; ABCG1: Adenosine triphosphate–binding cassette transporter G-1 protein; LCAT: Lecithin–cholesterol acyltransferase; SR-B1: Scavenger receptor B1; PON1: Paraoxonase-1; LRP: Lipoprotein-like receptor; VEC: Vascular endothelial cells; MCP-1: Monocyte chemoattractant protein-1; HDL: High-density lipoprotein. After Kaysen[74], 2009.

Figure 6

Premature death related to heart failure in haemodialysis. After Harnett et al[81], 1995.

Figure 7

Interplay between calcium, phosphate, calcitriol and Fibroblast growth factor-23 in chronic kidney disease. FGF: Fibroblast growth factor; CKD: Chronic kidney disease.

Figure 8

The association between chronic kidney disease and coronary heart disease. Adapted from Hage FG 2009[67].