A new rescue regimen with plasma exchange and rituximab in high-risk membranous glomerulonephritis

Background Even though current treatment guidelines for idiopathic membranous glomerulonephritis (iMGN) exist, many questions regarding an optimal therapy remain unanswered. Complete remission cannot be achieved in all patients; relapses occur, in some cases frequently, and side effects from the immunosuppressive therapy are common. Therapeutic options in high‐risk patients not responding to standard immunosuppressive therapies are limited. Recent research reveals that the human M‐type phospholipase A2 receptor (PLA2R) is a causative factor in iMGN that parallels clinical disease activity. However, in some patients, this correlation is not evident and additional undetermined factors seem to play a role. Design We evaluated a new rescue protocol including plasma exchanges (PE) against albumin, intravenous immunoglobulins (IVIGs) and rituximab for 10 patients with a biopsy‐proven diagnosis of iMGN who were therapy‐resistant to all conventional regimens and had a urinary protein to creatinine ratio of more than 10 000 mg/g Crea. We compared this protocol with standard immunosuppressive protocols including monthly alternating prednisolone plus cyclophosphamide (18 patients), cyclosporine plus prednisolone (23 patients) and rituximab alone (eight patients) in a retrospective design. Results Our rescue regimen with PE, IVIGs and rituximab achieved partial remission in 90% of patients who had been otherwise refractory to therapy. The mean time to partial remission was 2·1 months. Furthermore, two anti‐PLA2R‐antibody negative patients were also treated with this rescue regimen, achieving partial remission after 1 and 4 months. Conclusion A combination of PE, IVIGs and rituximab is a treatment option to consider for high‐risk patients with iMGN who are refractory to conventional therapy.