Efficacy of LDL Apheresis in Inducing Remission in Refractory Minimal Change Nephrotic Syndrome: A Case Series of Four Patients

Minimal change nephrotic syndrome (MCNS) generally responds well to corticosteroid therapy; however, a subset of patients experience refractory or relapsing disease with limited treatment options. Low-density lipoprotein apheresis (LDL-A), initially developed for familial hypercholesterolemia, has been used in Japan since the late 1980s as an adjunctive therapy for refractory focal segmental glomerulosclerosis (FSGS), with favorable clinical outcomes. While LDL-A remains rarely performed internationally, Japanese clinical experience has demonstrated its efficacy, leading to expansion of its health insurance indication in 2024 to include MCNS and membranous nephropathy. Nevertheless, published evidence for MCNS remains scarce. We report four patients with refractory MCNS in whom LDL-A contributed to remission induction, aiming to emphasize its potential as a supportive therapeutic option.

Between April 2019 and March 2024, five patients with nephrotic syndrome underwent LDL-A at our institution. Four were diagnosed with MCNS based on renal biopsy or clinical course and were retrospectively analyzed. Clinical characteristics, laboratory data, treatment regimens, and outcomes were reviewed. LDL-A was performed twice weekly using a double-filtration system with primary plasma filters (Plasmaflo OP-08D) and secondary adsorption columns (Liposorber LA-15 or LA-40), with approximately 3,000 mL plasma processed per session. Anticoagulation was achieved with unfractionated heparin, and treatment duration was tailored to the clinical course.

Case 1: A 74-year-old man with new-onset MCNS and diabetes mellitus developed oliguria requiring hemodialysis and was resistant to high-dose steroid pulses. Three LDL-A sessions rapidly decreased proteinuria, enabling dialysis withdrawal. Case 2: A 74-year-old woman with recurrent MCNS relapsed despite prednisolone and cyclosporine. Three LDL-A sessions achieved improvement, even after cyclosporine discontinuation due to hepatotoxicity. Case 3: An 18-year-old man with initial MCNS presented with severe nephrotic syndrome and oliguria requiring dialysis. Steroids and cyclosporine were ineffective, but two LDL-A sessions improved urine output and proteinuria, allowing dialysis withdrawal. Case 4: A 57-year-old woman with new-onset MCNS and profound hypoalbuminemia relapsed during steroid tapering. Four LDL-A sessions in combination with immunosuppressants markedly reduced proteinuria and normalized serum albumin. All patients tolerated LDL-A without major adverse events. Clinical benefits included rapid reduction of proteinuria, facilitation of dialysis withdrawal in dialysis-dependent cases, and reduction in immunosuppressant exposure.

This case series suggests that LDL-A is a safe and effective adjunctive therapy for remission induction in refractory MCNS. Although scarcely used outside Japan, decades of Japanese experience have validated its role in FSGS, and recent insurance expansion has extended its indication to MCNS. Our findings demonstrate that LDL-A can provide significant clinical benefit, particularly for patients resistant to immunosuppressants, intolerant to drug intensification, or requiring dialysis. Broader application of LDL-A, potentially including newer centrifugal systems, may enhance global accessibility. Larger prospective studies are warranted to define its optimal use in MCNS.