Journal Article

Rituximab therapy in nephrotic syndrome: implications for patients' management

Sinha, Aditi, Bagga, Arvind

2013

Overview

Rituximab offers an alternative approach to current immunosuppressive therapies for patients with difficult-to-treat, steroid-dependent nephrotic syndrome. Rituximab therapy has been shown to induce and maintain remission in these patients; however, most data are derived from anecdotal reports or case series. This Review provides an overview of available data on the safety and efficacy of rituximab in the treatment of paediatric and adult patients with nephrotic syndrome. Rituximab offers an alternative to current immunosuppressive therapies for difficult-to-treat nephrotic syndrome. The best outcomes are seen in patients with steroid-dependent nephrotic syndrome who have failed to respond to multiple therapies. By contrast, the benefits of rituximab therapy are limited in patients with steroid-resistant nephrotic syndrome, particularly those with focal segmental glomerulosclerosis (FSGS). Therapy with plasma exchange and one or two doses of rituximab has shown success in patients with recurrent FSGS. Young patients and those with normal serum albumin at recurrence of nephrotic syndrome are most likely to respond to rituximab therapy. A substantial proportion of rituximab-treated patients with idiopathic membranous nephropathy show complete or partial remission of proteinuria, and reduced levels of phospholipase A 2 receptor autoantibodies, which are implicated in the pathogenesis of this disorder. Successful rituximab therapy induces prolonged remission and enables discontinuation of other medications without substantially increasing the risk of infections and other serious adverse events. However, the available evidence of efficacy of rituximab therapy is derived chiefly from small case series and requires confirmation in prospective, randomized, controlled studies that define the indications for use and predictors of response to this therapy. Key Points Therapy with rituximab induces and maintains remission effectively in patients with difficult-to-treat, steroid-dependent nephrotic syndrome; sustained remission enables the reduction of steroid doses and withdrawal of calcineurin inhibitors In patients with steroid-resistant nephrotic syndrome who fail to respond to treatment with calcineurin inhibitors, the response to rituximab therapy is less efficacious Rituximab dose(s), the rate of B-cell recovery and clinical response are not closely correlated Combined therapy with rituximab and plasma exchange might be useful to prevent or treat recurrence of focal segmental glomerulosclerosis Therapy with rituximab should be considered in patients with idiopathic membranous nephropathy who fail to respond to treatment with cyclophosphamide or calcineurin inhibitors Acute infusion reactions are frequent but transient in patients who receive rituximab; serious adverse effects, including an increased risk of infections, are uncommon

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/61/51/1568 / 631/92/436/108 / 631/92/609 / 692/699/1585 / Animals / Antibodies, Monoclonal, Murine-Derived - immunology / Antibodies, Monoclonal, Murine-Derived - therapeutic use / Antigens / Apoptosis / Drug therapy / Glomerulosclerosis, Focal Segmental - immunology / Humans / Immunologic Factors - immunology / Immunologic Factors - therapeutic use / Kidney diseases / Kinases / Lupus / Lymphocyte Depletion / Medicine / Medicine & Public Health / Nephrology / Nephrotic syndrome / Nephrotic Syndrome - drug therapy / Nephrotic Syndrome - immunology / Pathogenesis / Plasma Exchange / Proteins / Remission (Medicine) / review-article / Rituximab / Steroids / Transplants & implants / Treatment Outcome