Lipoprotein(a) in the nephrotic syndrome: Molecular analysis of lipoprotein(a) and apolipoprotein(a) fragments in plasma and urine

Plasma levels of lipoprotein(a) (Lp(a)), an atherogenic particle, are eleva ted in kidney disease, which suggests a role of this organ in the metabolis m of Lp(a). Additional evidence for a role of the kidney in the clearance o f Lp(a) is provided by the fact that circulating N-terminal fragments of ap olipoprotein(a) (apo(a)) are processed and eliminated by the renal route. T o further understand the mechanism underlying such renal excretion, the lev els of apo(a) fragments in plasma and urine relative to plasma Lp(a) levels were determined in patients with nephrotic syndrome (n = 15). In plasma, t he absolute (24.7 +/- 20.4 versus 2.16 +/- 2.99 mu g/ml, P < 0.0001) as wel l as the relative amounts of apo(a) fragments (4.6 +/- 3.4% versus 2.1 +/- 3.3% of total Lp(a), P < 0.0001) were significantly elevated in nephrotic p atients compared with a control, normolipidemic population. In addition, ur inary apo(a) excretion in patients with nephrotic syndrome was markedly ele vated compared with that in control subjects (578 +/- 622 versus 27.7 +/- 4 4 ng/ml per mg creatinine, P < 0.001). However, the fractional catabolic ra tes of apo(a) fragments were similar in both groups (0.68 +/- 0.67% and 0.6 2 +/- 0.47% in nephrotic and control subjects, respectively), suggesting th at increased plasma concentrations of apo(a) fragments in nephrotic subject s are more dependent on the rate of synthesis rather than on the catabolic rate. Molecular analysis of apo(a) immunoreactive material in urine reveale d that the patterns of apo(a) fragments in nephrotic patients were distinct from those of control subjects. Full-length apo(a), large N-terminal apo(a ) fragments similar in size to those present in plasma, as well as C-termin al fragments of apo(a) were detected in urine from nephrotic patients but n ot in urine from controls. All of these apo(a) forms were in addition to sm aller N-terminal apo(a) fragments present in normal urine. This study also demonstrated the presence of Lp(a) in urine from nephrotic patients by ultr acentrifugal fractionation. These data suggest that in nephrotic syndrome, Lp(a) and large fragments of apo(a) are passively filtered by the kidney th rough the glomerulus, whereas smaller apo(a) fragments are secreted into th e urine.