Lipoprotein(a) Serum Levels and Apolipoprotein(a) Phenotypes in Children with Chronic Renal Disease

Abstract

ABSTRACT. Lipoprotein(a) [Lp(a)] has recently beenLp(a) is a cholesterol-rich lipoprotein resembling LDL, but characterized as a genetically determined risk factor for with a different protein composition, consisting of apo B-100 atherosclerosis and thrombosis. Normally, Lp(a) serum and apo(a). Increased blood concentrations of Lda) are strongly levels are closely related to the apo(a) phenotype. We associated with an increased risk for atherosclerosis (8-10) and studied Lp(a) serum levels and apo(a) phenotypes in 136 arterial and venous thrombosis (1 1). Notably in Young patients, young subjects, aged 0.8-24.7 y, including patients with Lda) appears to be an independent risk factor for myocardial glomerular disease and normal renal function (n = 28), infarction ( 12). The proatherogenic and prothrombotic effects of patients with chronic renal failure (n = 201, patients treated Lp Of all, 21 patients had proteinuria in the nephrotic range. and interference with the fibrinol~tic system (8, 99 13). ~h~ distribution of Lp(a) levels in normal subjects wasIn adult Caucasian populations, Lp(a) blood levels are usually skewed to the left with 97% having levels below 300 mg/ low, i.e. the distribution of normal values is shifted to the left; blood levels above 250-300 mg/L indicate a significant risk for L' A subpopulation with increased Lp(a) levels (13-42%) vascular complications, particularly in patients with elevated could be detected in all groups with renal disease, and LDL cholesterol levels (13-15). increased mean serum L P (~) levels were found in patients In individuals, L~~) serum levels are under genetic with ne~hrotic range proteinuria, in patients with chronic control and dependent on the phenotype of the apoprotein renal failure, and in patients on peritoneal dialysis. Serum apo(a). According to Utemann el (16), seven phenotypes of Lda) levels were not with age, gender, type Of different molecular weight can be differentiated by their relative renal disease, renal function or severity of proteinuria, but mobilities to apo B-100 on electrophoresis; these have been were ~ornelat* with the apo(a) phenotype. For a given designated F (faster than B-100), B (similar to B-loo), S 1, S2, phen?w9 Lda) levels knded t 0 . h higher in patients S3, S4 (all slower than B-loo), and 0 (not detectable). Serum than controls. We ~onclude that increased Lda) serum levels of Lp(a) show an inverse correlation with the size of the levels are frequently found in Young patients with chronic apoprotein phenotype, i.e. small phenotypes (F, B, Sl) are assorenal disease, possibly predisposing them to an increased ciated with high and larger phenotypes (S3, S4) with low serum risk for atherosclerosis and thrombosis. (Pediatr Res 34: levels of Lp(a) (16). Although Lp(a) levels for a given phenotype 772-776,1993) show considerable overlap, it was concluded that about 40% of the variability in the Lp(a) serum concentrations can be exAbbreviations plained by the apo(a) phenotype (17). Other researchers have identified a greater number of ...

Lipoprotein (a): impact by ethnicity and environmental and medical conditions

“…Further, a mild glomerular filtration rate impair ment was associated with a higher Lp(a) level in a recent study of diabetic patients (172). In other studies, however, Lp(a) concentrations did not differ from those of controls (173)(174)(175)(176)(177). In a large multicenter study, Kronenberg et al (145) reported higher Lp(a) levels in patients undergoing continuous ambulatory peritoneal dialysis compared with HD.…”

Effect of Individual Plasma Lipoprotein(a) Variations In Vivo on Its Competition With Plasminogen for Fibrin and Cell Binding

“…were still higher at 6 months of remission compared with levels previously reported for children 14,15 and by reference to an age-matched control population of children composed of 109 boys and 91 girls.…”

“…5,51 Marked lipid abnormalities, such as elevation of lipoproteins containing apo B, ie, VLDL, LDL, and Lp(a), have been previously reported 52 and were confirmed by results of the present studies. Nephrotic children have significantly higher plasma concentrations of Lp(a) than do healthy children 14,15,[53][54][55][56] ; these high levels of Lp(a) are an abnormality currently considered to be an independent risk factor for the development of cardiovascular disease in the general population. 18 The mechanism by which Lp(a) may favor the atherothrombotic process may be related to the lysine-binding properties of apo(a).…”

“…9,10 In contrast, increased concentrations of Lp(a), the lipoprotein particle containing apo(a), a glycoprotein genetically related and structurally homologous to plasminogen, have been reported in nephrotic adults 9,[11][12][13] and in children. 14,15 Because high plasma levels of Lp(a) are now recognized as a risk factor in cerebrovascular and cardiovascular diseases, 16 -18 increased concentrations of Lp(a) may represent an added thrombotic risk in nephrotic subjects. 19,20 Plasminogen and apo(a) contain triple-loop disulfidelinked structures called "kringles" and a serine-proteinase domain.…”

“…27 Data concerning the distribution of these apo(a) isoforms in children with renal diseases are scarce. 14 Some of the plasminogen-like kringle 4 copies endow apo(a) with the ability to compete with plasminogen for binding to cells 28,29 and fibrin. 30,31 However, the substitution of the Arg-Val plasminogen cleavage site by Ser-Ile in apo(a) impairs the generation of plasmin-like activity by activators.…”