CARDIOVASCULAR AND SURVIVAL PARADOXES IN DIALYSIS PATIENTS: Kinetic Studies of Atherogenic Lipoproteins in Hemodialysis Patients: Do They Tell Us More about Their Pathology?

Patients with chronic kidney disease have one of the highest risks for atherosclerotic complications. Several large epidemiological studies described an opposite association of total and low density lipoprotein (LDL) cholesterol with cardiovascular complications and total mortality compared to the general population, a circumstance often called “reverse epidemiology.” Many factors might contribute to this reversal such as interaction with malnutrition/inflammation, pronounced fluctuations of atherogenic lipoproteins during the course of renal disease, heterogeneity of lipoprotein particles with preponderance of remnant particles, and chemical modification of lipoproteins caused by the uremic environment. A vicious cycle has been suggested in uremia in which the decreased catabolism of atherogenic lipoproteins such as LDL, IDL and Lp(a) leads to their increased plasma residence time and further modification of these lipoproteins by oxidation, carbamylation, and glycation. Using stable isotope techniques, it has been shown recently that the plasma residence time of these particles is more than twice as long in hemodialysis patients as in nonuremic subjects. This reduced catabolism, however, is masked by the decreased production of LDL, resulting in near‐normal plasma levels of LDL. The production rate of Lp(a) in hemodialysis patients is similar to that in controls which together with the doubled residence time results in elevated Lp(a) levels. An increased clearance of these altered lipoproteins via the scavenger receptors of macrophages leads to the transformation of macrophages into foam cells in the vascular wall and might contribute to the pronounced risk for cardiovascular complications of these patients. These observations suggest that the real danger of these particles is not reflected by the measured concentrations but by their metabolic qualities.