Long-term Low-density Lipoprotein Apheresis in a Patient with Refractory Idiopathic Membranous Glomerulonephritis

Abstract

A 61-year-old Japanese man developed nephrotic syndrome (NS) due to idiopathic membranous glomerulonephritis (MGN). He received immunosuppressive therapy for two years, including prednisolone, cyclophosphamide, and cyclosporine A, but the NS persisted. Low-density lipoprotein apheresis (LDL-A) was initiated at a frequency of twice a month and continued for 9 years (203 sessions in total). His proteinuria reduced to less than 1 g daily after 9 years. LDL-A was stopped, and the NS has not relapsed for five years. This case suggests that long-term LDL-A therapy may be a treatment option for idiopathic MGN refractory to immunosuppressive therapy or short-term LDL-A.

Is There a Place for Apheresis in the Management of Idiopathic Membranous Nephropathy? A Report of Three Cases and Literature Review

“…Several published clinical cases have demonstrated the effectiveness of adding apheresis (double-filtration plasmapheresis (DFPP), plasma exchange) for patients with membranous nephropathy refractory to standard immunosuppressants, with a favorable evolution of nephrotic syndrome [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. Various hypotheses, apart from the elimination of autoantibodies, were considered, including: Elimination of LDL cholesterol: Enhancing the bioavailability of immunosuppressants (cyclophosphamide, calcineurin inhibitors, and steroids) and mitigating the glomerular toxicity associated with dyslipidemia [ 25 , 26 ].…”

“… Elimination of complement proteins and inflammatory cytokines: Supported by the efficacy of apheresis in seronegative membranous nephropathy [ 32 ]. Yabuuchi et al [ 27 ] reported a case of a 61-year-old patient with idiopathic membranous nephropathy, primarily IgG4 on kidney biopsy, and treated unsuccessfully with corticosteroids, cyclophosphamide, and cyclosporine for 2 years. Following the initiation of DFPP at a rate of two sessions per month, partial remission was achieved, with proteinuria decreasing to less than 3 g/24 h after 4 years and less than 1 g/24 h after 9 years.…”

“…Several published clinical cases have demonstrated the effectiveness of adding apheresis (double-filtration plasmapheresis (DFPP), plasma exchange) for patients with membranous nephropathy refractory to standard immunosuppressants, with a favorable evolution of nephrotic syndrome [23][24][25][26][27][28][29][30][31]. Various hypotheses, apart from the elimination of autoantibodies, were considered, including:…”

“…Anti-PLA2R autoantibodies and IgG rebounded upon stopping IA before gradually decreasing during follow-ups, suggesting the potential need for combined therapy targeting B cells to avoid a rebound. These sessions resulted in an increase in serum albumin concentrations from 20.5 [19-21.25] g/L to 21.5 [19.25-25.25] g/L, 23 [20][21][22][23][24] g/L, and 25 [23][24][25][26][27][28] g/L after 12, 24, and 52 weeks, respectively (p < 0.001). However, there were no significant changes in proteinuria and renal function.…”