Abstract
Lipoprotein (a) [Lp(a)] and its measurement, structure and function, the impact of ethnicity and environmental factors, epidemiological and genetic associations with vascular disease, and new prospects in drug development have been extensively examined throughout this Thematic Review Series on Lp(a). Studies suggest that the kidney has a role in Lp(a) catabolism, and that Lp(a) levels are increased in association with kidney disease only for people with large apo(a) isoforms. By contrast, in those patients with large protein losses, as in the nephrotic syndrome and continuous ambulatory peritoneal dialysis, Lp(a) is increased irrespective of apo(a) isoform size. Such acquired abnormalities can be reversed by kidney transplantation or remission of nephrosis. In this Thematic Review, we focus on the relationship between Lp(a), chronic kidney disease, and risk of cardiovascular events.
Highlights
Lipoprotein (a) [Lp(a)] and its measurement, structure and function, the impact of ethnicity and environmental factors, epidemiological and genetic associations with vascular disease, and new prospects in drug development have been extensively examined throughout this Thematic Review Series on Lp(a)
We will summarize the complex interrelationships between Lp(a) levels and kidney function, and we will consider the insight this can offer into Lp(a) metabolism, the potential importance of Lp(a) for risk of vascular disease in patients with chronic kidney disease (CKD), and whether novel Lp(a)-lowering therapies might have a role in preventing cardiovascular disease in such patients
CKD is defined as the presence of kidney damage (manifesting as albuminuria, or determined by radiological or Abbreviations: CKD, chronic kidney disease; estimated GFR (eGFR), estimated glomerular filtration rate; ESRD, end-stage renal disease; GFR, glomerular filtration rate; Lp(a), lipoprotein (a); peritoneal dialysis, continuous ambulatory peritoneal dialysis
Summary
CKD is defined as the presence of kidney damage (manifesting as albuminuria, or determined by radiological or Abbreviations: CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; GFR, glomerular filtration rate; Lp(a), lipoprotein (a); peritoneal dialysis, continuous ambulatory peritoneal dialysis. In a stable isotope study of five patients with the nephrotic syndrome versus five control subjects [with varying apo(a) isoform sizes], despite higher Lp(a) levels in the nephrotic patients, the fractional catabolic rate was comparable between the two groups, suggesting increased synthesis may be the cause of high Lp(a) in these patients [60]. The 4D study of 1,255 hemodialysis patients with type 2 diabetes reported no association of higher ln Lp(a) levels or small apo(a) isoforms with combined cardiovascular events (hazard ratio, 1.04; 95% CI, 0.97–1.11; P = 0.30); significant associations of Lp(a) levels with all-cause mortality and fatal infections were reported overall, and in patients 66 years of age [99] These associations were based on relatively small numbers of events, 599 deaths including 123 deaths from infection, and more data are needed to explore the relationship of Lp(a) with infection. The available evidence in CKD populations suggests that, to the general population, those with high Lp(a) levels are at increased risk of cardiovascular disease, it remains unclear whether the increased risk is apo(a) isoform size dependent
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