Lipoprotein(a) serum concentrations and apolipoprotein(a) phenotypes in mild and moderate renal failure.
High lipoprotein(a) (Lp(a)) serum concentrations and the underlying apolipoprotein(a) (apo(a)) phenotypes are risk factors for cardiovascular disease in the general population as well as in patients with renal disease. Lp(a) concentrations are markedly elevated in patients with end-stage renal disease. However, nothing is known about the changes of Lp(a) depending on apo(a) size polymorphism in the earliest stages of renal impairment. In this study, GFR was measured by iohexol technique in 227 non-nephrotic patients with different degrees of renal impairment and was then correlated with Lp(a) serum concentrations stratified according to low (LMW) and high (HMW) molecular weight apo(a) phenotypes. Lp(a) increased significantly with decreasing GFR. Such an increase was dependent on apo(a) phenotype. Only renal patients with HMW apo(a) phenotypes expressed higher median Lp(a) concentrations, i.e., 6.2 mg/dl at GFR >90 ml/min per 1.73 m2, 14.2 at GFR 45 to 90 ml/min per 1.73 m2, and 18.0 mg/dl at GFR <45 ml/min per 1.73 m2. These values were markedly different when compared with apo(a) phenotype-matched control subjects who had a median level of 4.4 mg/dl (ANOVA, linear relationship, P < 0.001). In contrast, no significant differences were observed at different stages of renal function in patients with LMW apo(a) phenotypes when compared with phenotype-matched control subjects. The elevation of Lp(a) was independent of the type of primary renal disease and was not related to the concentration of C-reactive protein. Multiple linear regression analysis found that the apo(a) phenotype and GFR were significantly associated with Lp(a) levels. Non-nephrotic-range proteinuria modified the association between GFR and Lp(a) levels. In summary, an increase of Lp(a) concentrations, compared with apo(a) phenotype-matched control subjects, is seen in non-nephrotic patients with primary renal disease even in the earliest stage when GFR is not yet subnormal. This change is found only in subjects with HMW apo(a) phenotypes, however.
Kronenberg
Florian
F
Institute of Medical Biology and Human Genetics, University of Innsbruck, Austria.
Kuen
Erich
E
Institute of Medical Biology and Human Genetics, University of Innsbruck, Austria.
Ritz
Eberhard
E
Department of Internal Medicine, Division of Nephrology, Ruperto-Carola-University, Heidelberg, Germany.
Junker
Ralf
R
Institute of Clinical Chemistry and Laboratory Medicine and Institute of Arteriosclerosis Research, University of Münster, Germany.
König
Paul
P
Innsbruck University Hospital, Department of Clinical Nephrology, Innsbruck, Austria.
Kraatz
Günter
G
Department of Internal Medicine A, Ernst-Moritz-Arndt-University, Greifswald, Germany.
Lhotta
Karl
K
Innsbruck University Hospital, Department of Clinical Nephrology, Innsbruck, Austria.
Mann
Johannes F E
JFE
München Schwabing Hospital, LMU, Munich, Germany.
Müller
Gerhard A
GA
Department of Nephrology and Rheumatology, Georg-August-University, Göttingen, Germany.
Neyer
Ulrich
U
Feldkirch Hospital, Department of Nephrology, Feldkirch, Austria.
Riegel
Werner
W
Medizinische Universitätskliniken des Saarlandes, Innere Medizin IV, Homburg/Saar, Germany.
Riegler
Peter
P
Bozen Hospital, Division of Nephrology and Hemodialysis, Bozen, Italy.
Schwenger
Vedat
V
Department of Internal Medicine, Division of Nephrology, Ruperto-Carola-University, Heidelberg, Germany.
VON Eckardstein
Arnold
A
Institute of Clinical Chemistry and Laboratory Medicine and Institute of Arteriosclerosis Research, University of Münster, Germany.
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001054:Apolipoproteins A / Q000097:blood* / Q000235:genetics; D015415:Biomarkers / Q000032:analysis; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D016014:Linear Models; D017270:Lipoprotein(a) / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D011110:Polymorphism, Genetic; D011379:Prognosis; D012016:Reference Values; D051437:Renal Insufficiency / Q000097:blood* / Q000503:physiopathology; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D001054:Apolipoproteins A; D015415:Biomarkers; D017270:Lipoprotein(a)