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Lipoprotein(a) serum concentrations and apolipoprotein(a) phenotypes in mild and moderate renal failure
Florian Kronenberg1, Erich Kuen1, Eberhard Ritz2
1Institute of Medical Biology and Human Genetics, University of Innsbruck, Austria.
Insights
High lipoprotein(a) (Lp(a)) levels increase with declining kidney function, particularly in individuals with high molecular weight apolipoprotein(a) (apo(a)) phenotypes. This elevation occurs even in early renal impairment stages.
Area of Science:
- Cardiovascular Medicine
- Nephrology
- Clinical Chemistry
Background:
- High lipoprotein(a) (Lp(a)) serum concentrations and apolipoprotein(a) (apo(a)) phenotypes are established cardiovascular disease risk factors.
- Lp(a) levels are significantly elevated in patients with end-stage renal disease.
- The impact of apo(a) size polymorphism on Lp(a) levels in early renal impairment remains unknown.
Purpose of the Study:
- To investigate changes in Lp(a) serum concentrations in relation to apo(a) size phenotypes and varying degrees of renal impairment.
- To determine if Lp(a) elevation in early renal disease is dependent on apo(a) phenotype.
Main Methods:
- Measured glomerular filtration rate (GFR) using the iohexol technique in 227 non-nephrotic patients with varying renal function.
- Correlated Lp(a) serum concentrations with GFR, stratified by low (LMW) and high (HMW) molecular weight apo(a) phenotypes.
- Utilized ANOVA and multiple linear regression analysis to assess associations.
Main Results:
- Lp(a) concentrations increased significantly with decreasing GFR, a phenomenon dependent on apo(a) phenotype.
- Patients with HMW apo(a) phenotypes showed significantly higher median Lp(a) levels with declining GFR compared to controls.
- No significant differences in Lp(a) levels were observed in patients with LMW apo(a) phenotypes across different GFR stages compared to controls.
Conclusions:
- Elevated Lp(a) concentrations are observed in non-nephrotic patients with primary renal disease, even with GFR not yet subnormal.
- This Lp(a) elevation is specific to individuals with HMW apo(a) phenotypes.
- The apo(a) phenotype and GFR are significant determinants of Lp(a) levels in early renal impairment.
Abstract:
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.