INCREASED ATHEROGENICITY OF LOW-DENSITY-LIPOPROTEIN IN HEAVY PROTEINURIA

Background. Heavy proteinuria is associated with marked abnormalities of lipoprotein metabolism and increased risk of atherogenesis. It is p ossible that qualitative as well as quantitative changes occur in lipo proteins to contribute to increased cardiovascular risk; for example, it is known that LDL exhibits heterogeneity, with small, dense LDL III particles being more atherogenic. Methods. We investigated LDL subfra ctions (measured by density gradient ultracentrifugation), VLDL subfra ctions, and post-heparin lipases in 12 patients with primary glomerula r disease and 24-h albuminuria >2.5 g. These were compared to 23 age-a nd sex-matched controls. Results. Total LDL concentrations were simila r in proteinuric patients and controls; however, there was a shift in subfraction distribution. The larger LDL I and LDL II particles were l ower in the proteinuric group (29 +/- 24 vs 62 +/- 26 mg/dl P = 0.011 and 121 +/- 80 vs 197 + 74 mg/dl P=0.028), whereas the concentration o f atherogenic LDL III (small dense) was higher (135 +/- 64 vs 75 +/- 7 1 mg/dl P=0.0016). The concentration of total VLDL and both its subfra ctions were increased in the patients with proteinuria. Post-heparin h epatic and lipoprotein lipase levels were similar to normal. Conclusio ns. These findings suggest that the atherogenicity of LDL is increased in patients with heavy proteinuria because of the redistribution towa rds smaller denser particles. Since small, dense LDL has a lower affin ity for the LDL receptor, the altered nature of the lipoprotein in pro teinuria may decrease its clearance by the receptor-mediated pathway a nd contribute to the reduced clearance of LDL observed in this populat ion. This may contribute to progression of renal failure or the accele rated vascular disease found in patients with heavy proteinuria.