Lipoprotein(a) in nephrotic syndrome and end-stage renal disease

Lipoprotein(a) [Lp(a)] may be elevated in patients with the nephrotic syndrome and patients on hemodialysis or continuous ambulatory peritoneal dialysis. High levels of Lp(a) are due to proteinuria or an activated acute-phase response. Serum concentrations greater than 30 mg/dl are independently associated with coronary heart disease. Data from cell culture studies suggest that it is not uptake of Lp(a) by mesangial cells but trapping by matrix proteins that contributes to the generation of glomerular apo(a) deposits. Lp(a) alters mesangial cell DNA synthesis and stimulates the generation of reactive oxygen species. Prolonged exposure to Lp(a) causes mesangial cell death in vitro culture' experiments. Lp(a) does not alter autocrine transforming growth factor-beta transcription in human mesangial cells and has, unlike low-density lipoprotein, no effect on the production of the extracellular matrix protein fibronectin. Future cell culture studies on the role of Lp(a) in renal disease have to address whether Lp(a) induces cell death via apoptosis and to what extent the generation of oxygen radicals is involved in this process.