BACKGROUND Hyperlipidemia is a common feature of the nephrotic syndrome (NS). From retrospective studies, it has been suggested that aggressive lipid-lowering with low-density lipoprotein apheresis (LDL-A) may not only improve dyslipidemia but also decrease urinary albumin excretion and increase serum levels of albumin in patients with focal segmental sclerosis. METHODS Seven patients (6 males) aged 44 +/-7 years (SEM) with NS (duration 29+/-11 months) of diverse etiologies were investigated in a prospective study. A fixed protocol of LDL-A was designed for treatment twice-a-week for 3 weeks and then once a week for 7 weeks. The effects of LDL-A on lipid parameters (cholesterol, triglycerides, HDL, Lp(a), apo A-I, apo B) and renal parameters (iohexol clearance, serum albumin and 24-h urinary albumin excretion) were evaluated. RESULTS Following treatment by LDL-A a remission in the severity of the NS was observed in two patients whereas a clear improvement was observed in four of the patients. A small, but significant (P<0.05), increase in serum albumin levels from 20+/-2 to 24+/-2 g L(-1) was noted after LDL-A. As expected, serum lipid parameters improved during LDL-A, and significant decreases in serum cholesterol, apo B and plasma Lp(a) were observed at different time-points of LDL-A. Conversely, no significant changes in either triglyceride, HDL or apo A-I levels were observed during LDL-A. CONCLUSIONS The present uncontrolled prospective study shows that LDL-A causes a rapid 30-40% decrease in serum cholesterol and plasma Lp(a) levels in patients with NS. The present prospective study also suggests that short-term LDL-A treatment may increase serum albumin levels in nephrotic patients.