The importance of immunological monitoring in the treatment of refractory membranous nephropathy: clinical case

Primary membranous nephropathy is the most common morphological variant of glomerulonephritis with nephrotic syndrome in the European ancestry. Immunosuppressive therapy is required in most cases of membranous nephropathy treatment. The choice of immunosuppressive drugs and the determination of therapy duration for this nephropathy cause significant difficulties. The role of monitoring immunological parameters in assessing the effectiveness of immunosuppressive therapy and its duration has been poorly studied. The clinical case report examines modern treatment methods for membranous nephropathy with refractory nephrotic syndrome and demonstrates, using a concrete clinical example, the significance of monitoring immunological parameters during immunosuppressive therapy.

A 62-year-old female patient had persistent edema of the lower extremities, as well as high levels of proteinuria and autoantibodies to phospholipase A₂ receptor (PLA₂R). The diagnosis of stage 2 membranous nephropathy was made based on the morphological findings of the renal biopsy. Initial treatment with corticosteroids resulted only in a short-term improvement. Adding cyclosporine to steroid therapy also failed to achieve stable remission of the disease. Two infusions of rituximab (1 g each) in combination with methylprednisolone (16 mg) led to partial remission of the disease by the fifth month (22 weeks later) after administration of the 2nd dose of rituximab, complete remission was achieved by the sixth month (27 weeks later). By this time, the levels of proteinuria and PLA₂R antibodies had significantly decreased. However, monitoring of the B-system immune parameters showed increased urinary excretion of IgG and IgA, depending on the damage to the glomerular filtration barrier, which was the reason for the 3rd infusion of rituximab. Laboratory tests conducted 5 months after the administration of the 3rd dose of rituximab confirmed maintained clinical remission and restoration of immunoglobulin levels to the reference values.

This clinical observation confirms that the use of rituximab in combination with methylprednisolone is an effective method of refractory membranous nephropathy treatment. This case report demonstrates the possibility of monitoring urinary IgG and IgA levels normalized to urine creatinine level to assess the effectiveness of rituximab therapy and determine its optimal duration.