Renovascular arteriovenous differences in Lp[a] plasma concentrations suggest removal of Lp[a] from the renal circulation.

High plasma concentrations of lipoprotein[a] (Lp[a]) are considered a genetically determined risk factor for atherosclerosis. Lp[a] is produced by the liver. The site(s) and mechanism(s) of catabolism are presently unclear. Lp[a] is elevated secondary to end-stage renal disease which suggests a direct or indirect role of the kidney in the metabolism of Lp[a]. We therefore investigated, by a simple in vivo approach, whether Lp[a] is removed by the human kidney. Lp[a] plasma concentrations were measured simultaneously by various methods in the ascending aorta and renal vein of 100 patients undergoing coronary angiography or coronary angioplasty. Lp[a] levels differed significantly between the two vessels even after correcting for hemoconcentration (20.1 +/- 21.6 mg/dL versus 18.7 +/- 20.3 mg/dL, P < 0.001). This corresponds to a mean arteriovenous difference of -1.4 mg/ dL or -9% of the arterial concentration. No Lp[a] or intact apo[a] could be detected in urine from healthy probands. Although we cannot assign the kidney a regulatory role for Lp[a] plasma levels in humans with normal renal function, we conclude from our data that substantial amounts of this atherogenic lipoprotein are taken up by the kidney. The underlying mechanisms are unknown at the moment. This study therefore demonstrates for the first time that the human kidney plays an active role in the catabolism of Lp[a]. This may explain the elevated Lp[a] concentrations found in patients with chronic renal insufficiency.