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Apolipoprotein(a) phenotypes and lipoprotein(a) concentrations in patients with renal failure
H J Milionis1, M S Elisaf, A Tselepis
1Laboratory of Biochemistry, University of Ioannina, Greece.
Insights
Patients with renal failure exhibit elevated lipoprotein(a) [Lp(a)] levels, particularly those with high-molecular-weight apolipoprotein(a) [apo(a)] isoforms. This finding holds true across various stages of kidney disease, including dialysis.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Human Genetics
Background:
- Renal failure is linked to increased atherosclerotic disease risk.
- Elevated serum lipoprotein(a) [Lp(a)] is common in renal failure patients.
- Apolipoprotein(a) [apo(a)] gene variants influence Lp(a) levels in the general population.
Purpose of the Study:
- To investigate apolipoprotein(a) [apo(a)] phenotypes and serum lipoprotein(a) [Lp(a)] concentrations in patients with varying degrees of renal disease.
- To determine if apo(a) phenotypes explain elevated Lp(a) levels in renal failure.
- To assess Lp(a) levels in hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), and chronic renal failure (CRF) patients.
Main Methods:
- Studied 79 HD patients, 47 CAPD patients, 68 CRF patients (creatinine 1.8-8 mg/dL), and 73 healthy controls.
- Analyzed apo(a) phenotypes and measured serum Lp(a) concentrations in all groups.
- Compared Lp(a) levels and apo(a) isoform frequencies between patient groups and controls.
Main Results:
- All patient groups (HD, CAPD, CRF) showed significantly higher median serum Lp(a) than controls (7 mg/dL).
- Elevated Lp(a) levels were primarily associated with high-molecular-weight (HMW) apo(a) isoforms, not isoform frequencies.
- CAPD patients with low-molecular-weight (LMW) isoforms also showed increased Lp(a), an exception to the HMW association.
Conclusions:
- Elevated Lp(a) concentrations are prevalent in patients with renal failure, including mild/moderate CRF and end-stage renal disease (ESRD) on HD or CAPD.
- The increase in Lp(a) levels in renal failure patients is largely apo(a)-type specific, predominantly seen in those with HMW apo(a) phenotypes.
- HMW apo(a) isoforms are key contributors to elevated Lp(a) in renal failure, underscoring their role in cardiovascular risk in this population.
Abstract:
Patients with renal failure have an increased incidence of atherosclerotic disease. Numerous studies have shown that these patients show increased serum lipoprotein(a) [Lp(a)] concentrations compared with the control population. However, variable alleles at the apolipoprotein(a) [apo(a)] gene locus determine to a large extent the Lp(a) concentration in the general population. We therefore undertook the present study to evaluate apo(a) phenotypes and Lp(a) serum concentrations in a large number of patients with renal disease. Seventy-nine patients treated by hemodialysis (HD), 47 patients treated by continuous ambulatory peritoneal dialysis (CAPD), 68 patients with mild/moderate chronic renal failure (CRF) and serum creatinine levels of 1.8 to 8 mg/dL, and 73 healthy controls were studied. All patients showed significantly elevated median serum Lp(a) concentrations in comparison with controls: HD patients, 15.7 mg/dL (P < 0.01); CAPD patients, 20 mg/dL (P < 0. 005); CRF patients, 15.1 mg/dL (P < 0.01) versus controls, 7 mg/dL. The greater Lp(a) values in all groups were not explained by differences in isoform frequencies, whereas their increase was apo(a)-type specific. Thus, patients in all groups with high-molecular-weight (HMW) apo(a) isoforms showed a significant elevation of Lp(a) levels, whereas serum Lp(a) concentrations in patients with low-molecular-weight (LMW) isoforms were not significantly different from controls, except for CAPD patients, who presented increased serum Lp(a) concentrations. We conclude that in patients with renal failure, even of mild/moderate degree, as well as in patients with end-stage renal disease undergoing HD or CAPD, elevated Lp(a) concentrations are mainly observed in those with HMW apo(a) phenotypes.