ELEVATED PLASMA LIPOPROTEIN(A) IN PATIENTS WITH THE NEPHROTIC SYNDROME

Objective: To examine the influence of the nephrotic syndrome on lipop rotein(a) [Lp(a)], a plasma lipoprotein associated with atheroscleroti c cardiovascular disease independently of low-density lipoproteins. Fa ctors 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) pheno type has a significant effect on Lp(a) levels, apo(a) isoforms were de termined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting, and immunoblotting; the data were compared with a h ealthy control group. Results: Nephrotic patients had significantly hi gher 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 val ues greater than 30 mg/dL. Lipoprotein(a) levels correlated significan tly with apolipoprotein B, serum cholesterol, and low-density lipoprot ein 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 e levated 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 (nephropath y mean, 56 +/- 11 mg/dL versus dialysis mean, 34 +/- 4 10 mg/dL; n = 7 ). Conclusions. Most patients with the nephrotic syndrome have Lp(a) c oncentrations that are substantially elevated compared with controls o f the same apo(a) isoform. Because Lp(a) concentrations are substantia lly reduced when remission of the nephrotic syndrome is induced, it is likely that the nephrotic syndrome results directly in elevation of L p(a) by an as yet unknown mechanism. The high levels of Lp(a) in the n ephrotic syndrome could cause glomerular injury as well as increase th e risk for atherosclerosis and thrombotic events associated with this disorder.