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

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Abstract
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. A total of 62 patients: 47 with primary kidney disease and 15 with diabetic nephropathy. 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. Nephrotic patients had significantly higher Lp(a) levels (mean, SE, 69 10 mg/dL; median, 46 mg/dL, 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). 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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