Lipoprotein(a) serum concentrations and apolipoprotein(a) phenotypes in mild and moderate renal failure

High lipoprotein(a) (Lp(a)) serum concentrations and the underlying apolipo protein(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 disea se. 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 stu dy, GFR was measured by iohexol technique in 227 non-nephrotic patients wit h different degrees of renal impairment and was then correlated with Lp(a) serum concentrations stratified according to low (LMW) and high (HMW) molec ular weight apo(a) phenotypes. Lp(a) increased significantly with decreasin g GFR. Such an increase was dependent on apo(a) phenotype. Only renal patie nts 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 m(2), 14.2 at GFR 45 to 90 ml/ min per 1.73 m(2), and 18.0 mg/dl at GFR <45 ml/min per 1.73 m(2). These va lues were markedly different when compared with apo(a) phenotype-matched co ntrol subjects who had a median level of 4.4 mg/dl (ANOVA, linear relations hip, P < 0.001). In contrast, no significant differences were observed at d ifferent stages of renal function in patients with LMW apo(a) phenotypes wh en compared with phenotype-matched control subjects. The elevation of Lp(a) was independent of the type of primary renal disease and was not related t o the concentration of C-reactive protein. Multiple linear regression analy sis found that the apo(a) phenotype and GFR were significantly associated w ith Lp(a) levels. Non-nephrotic-range proteinuria modified the association between GFR and Lp(a) levels. In summary, an increase of Lp(a) concentratio ns, compared with apo(a) phenotype-matched control subjects, is seen in non -nephrotic patients with primary renal disease even in the earliest stage w hen GFR is not yet subnormal. This change is found only in subjects with HM W apo(a) phenotypes, however.