Low density lipoprotein apheresis therapy for steroid-resistant nephrotic syndrome

Background. The pathogenic role of hyperlipidemia in longstanding nephrotic syndrome (NS) is known to be responsible for both the progression of glome rulosclerosis and tubulointerstitial injury, especially in focal segmental glomerulosclerosis (FGS). Methods. Aggressive lipid lowering treatment by low density lipoprotein (LD L) apheresis (LDL-A) using a dextran sulfate cellulose column to treat pati ents with steroid-resistant or frequently recurrent severe NS was performed first without fixing the protocol in eight patients with FGS and one with minimal change nephrotic syndrome (MCNS). The period of NS before LDL-X, nu mber and average intervals of LDL-A until the end of the therapy, and the p rognosis were investigated. Next, a multicenter study with a fixed protocol of LDL-A treatment was designed in combination with steroid therapy for tr eatment twice a week for three weeks and weekly for six weeks. and was perf ormed in 17 patients with FGS. The effects on the state of NS in addition t o the change of urinary eicosanoid metabolites and remission rates were eva luated. Results. In the preliminary study, along with a rapid improvement of hyperl ipidemia, a high incidence of remission was achieved by LDL-A performed at relatively short intervals. In the multicenter study with a fixed protocol. there was a significant decrease of urinary protein (P < 0.001) and increa se of serum albumin (P < 0.02) as well as a decrease of thromboxane B-2 (Tx B(2)) excretion (P < 0.05) after the treatment. Urinary excretion of TXB2 w as significantly reduced after LDL-A (P < 0.05). The rate of entering into complete or incomplete remission was 71% with a relatively short duration o f nephrotic-range proteinuria using the LDL-A therapy in comparison with st eroid therapy alone. Conclusion. The rapid improvement of hypercholesterolemia with LDL-A treatm ent may provide a new approach for a high rate of improvement in the degree of NS in steroid-resistant NS of FGS and MCNS.