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Elevated Plasma Lipoprotein(a) in Patients with the Nephrotic Syndrome

Christoph Wanner; Daniel Rader; Werner Bartens; Jochen Kramer; H. Bryan Brewer; Peter Schollmeyer; and Heinrich Wieland
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From the University Hospital of Freiburg, Freiburg, Germany; the National Heart, Lung, and Blood Institute, Bethesda, Maryland. Requests for Reprints: Christoph Wanner, MD, Department of Medicine, Division of Nephrology, Hugstetterstr. 55 7800 Freiburg, Germany. Acknowledgments: The authors thank Glenda Talley, Marie Kindt, Barbara Winterrowd, Isolde Friedrich, and Petra Daemisch for their technical assistance. They also thank Gabriele Schulgen for statistical help. Grant Support: By a grant from the Deutsche Forschungsgemeinschaft Wa 836/1-1.

Copyright 2004 by the American College of Physicians

Ann Intern Med. 1993;119(4):263-269. doi:10.7326/0003-4819-119-4-199308150-00002
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Objective: To examine the influence of the nephrotic syndrome on lipoprotein(a) (Lp[a]), a plasma lipoprotein associated with atherosclerotic cardiovascular disease independently of low-density lipoproteins. Factors that modulate plasma Lp(a) concentrations are poorly understood.

Patients: A total of 62 patients: 47 with primary kidney disease and 15 with diabetic nephropathy.

Measurements: Lipoprotein(a) levels were determined by enzyme-linked immunosorbent assay. Because apo(a) phenotype has a significant effect on Lp(a) levels, apo(a) isoforms were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting, and immunoblotting; the data were compared with a healthy control group.

Results: Nephrotic patients had significantly higher Lp(a) levels (mean, SE, 69 10 mg/dL; median, 46 mg/dL, <0.01) compared with 91 healthy controls (mean, 18 2 mg/dL; median 9 mg/dL). Sixty percent of the patients and 18% of the controls had values greater than 30 mg/dL. Lipoprotein(a) levels correlated significantly with apolipoprotein B, serum cholesterol, and low-density lipoprotein cholesterol but showed no correlation with creatinine, albumin, or proteinuria. Within all apo(a) isoform classes, higher concentrations of Lp(a) were seen in the nephrotic patients compared with controls (P < 0.05). Finally, in nine patients with primary kidney disease and elevated Lp(a) levels, remission of the nephrotic syndrome was induced using immunosuppressive drugs and Lp(a) values decreased dramatically (pretreatment mean, 90 15 mg/dL versus remission mean, 31 8 mg/dL). A decrease in Lp(a) levels was also observed when patients with diabetic nephropathy progressed to end-stage renal disease (nephropathy mean, 56 11 mg/dL versus dialysis mean, 34 10 mg/dL; n = 7).

Conclusions: Most patients with the nephrotic syndrome have Lp(a) concentrations that are substantially elevated compared with controls of the same apo(a) isoform. Because Lp(a) concentrations are substantially reduced when remission of the nephrotic syndrome is induced, it is likely that the nephrotic syndrome results directly in elevation of Lp(a) by an as yet unknown mechanism. The high levels of Lp(a) in the nephrotic syndrome could cause glomerular injury as well as increase the risk for atherosclerosis and thrombotic events associated with this disorder.


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Figure 1.
Flow chart of the 62 patients with the nephrotic syndrome.

*Lipoprotein(a) determinations made. High Lp(a) at baseline was defined as a value greater than 30 mg/dL. Low Lp(a) at baseline includes the patient with an 0-allele.

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Figure 2.
Serum lipoprotein(a) values in patients with primary kidney disease (n = 9) before and after induction of remission of the nephrotic syndrome.P

Five patients with primary kidney disease were receiving no immunosuppressive therapy at time of resampling, and four were receiving monotherapy with cyclosporine but no steroids. Mean values SE are given by the vertical bars. ** = 0.001.

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Figure 3.
Serum lipoprotein(a) values in a group of patients (n = 10) with unremitted nephrotic syndrome.

At the time of follow-up (20 3.3 months after the initial measurement), patients were without immunosuppressive therapy. Mean values SE are shown by the vertical bars.

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Figure 4.
Serum lipoprotein(a) values in patients with diabetic nephropathy (n = 7) and after development of end-stage renal disease treated by dialysis.P

Mean values SE are shown by the vertical bars. * < 0.05.

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