Evidence for increased synthesis of lipoprotein(a) in the nephrotic syndrome.
In patients with the nephrotic syndrome, markedly increased levels of lipoprotein(a) (Lp(a)) concentration have been frequently reported, and it has been suggested that this may contribute to the increased cardiovascular risk in these patients. The mechanism, however, is not clear. In the present study, in vivo fractional synthesis rate of Lp(a) was measured using incorporation of the stable isotope 13C valine. Under steady-state conditions, fractional synthesis rate equals fractional catabolic rate (FCR). FCR of Lp(a) was estimated in five patients with the nephrotic syndrome and compared with five control subjects. The mean plasma Lp(a) concentration in the patients (1749+/-612 mg/L) was higher than in control subjects (553+/-96 mg/L). Two patients were heterozygous for apolipoprotein(a) (range, 19 to 30 kringle IV domains), whereas all control subjects were each homozygous with regard to apolipoprotein(a) phenotype (range, 18 to 28 kringle IV domains). The FCR of Lp(a) was comparable between control subjects (0.072+/-0.032 pools/d) and patients (0.064+/-0.029 pools/d) despite the wide variance in plasma concentration. This suggests that differences in Lp(a) levels are caused by differences in synthesis rate. Indeed, the absolute synthetic rate of Lp(a) correlated directly with plasma Lp(a) concentration (P < 0.0001) in all subjects. The present results demonstrate that increased synthesis, rather than decreased catabolism, causes elevated plasma Lp(a) concentrations in the nephrotic syndrome.
Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.
M G
MG
De Sain-Van Der Velden
D J
DJ
Reijngoud
G A
GA
Kaysen
M M
MM
Gadellaa
H
H
Voorbij
F
F
Stellaard
H A
HA
Koomans
T J
TJ
Rabelink
D000328:Adult; D053299:Apolipoprotein B-100; D001054:Apolipoproteins A / Q000235:genetics; D001055:Apolipoproteins B / Q000096:biosynthesis; D002318:Cardiovascular Diseases / Q000209:etiology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D008079:Lipoproteins, VLDL / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D012307:Risk Factors; D012709:Serum Albumin / Q000096:biosynthesis
D053299:Apolipoprotein B-100; D001054:Apolipoproteins A; D001055:Apolipoproteins B; D017270:Lipoprotein(a); D008079:Lipoproteins, VLDL; D012709:Serum Albumin