A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction

Abstract

IgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody-producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy-proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR<90 ml/min per 1.73 m, to receive standard therapy or rituximab with standard therapy. Primary outcome measures included change in proteinuria and change in eGFR. Median baseline serum creatinine level (range) was 1.4 (0.8-2.4) mg/dl, and proteinuria was 2.1 (0.6-5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in each group had ≥50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose-deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy.

IgA Nephropathy

“…A pilot trial evaluated the outcome of 34 patients with proteinuria.1 g/d and eGFR,90 ml/min per 1.73 m 2 randomized to rituximab versus conservative management. No effects on proteinuria or renal function were seen (67).…”

Immunoglobulin A Nephropathy: Advances in Understanding of Pathogenesis and Treatment

“…Results from a randomized controlled trial of rituximab in IgA nephropathy looking at the effects of depleting antibody-producing B cells were recently presented [53]. The study was a multicenter trial of 34 adult patients with biopsy-proven IgA nephropathy and proteinuria >1 g per day, maintained on ACEIs or ARBs with well-controlled blood pressure and eGFR <90 mL/min/1.73 m 2 , randomized to receive supportive therapy either alone or with rituximab.…”

Is it the time to offer rituximab as a cost-benefit treatment for immunoglobulin A nephropathy? A short-review to current concepts

“…IgAN frequently leads to progressive chronic kidney disease (CKD), thus it requires much attention to prevent or slow the course of disease. While there are some benefits to adding immunosuppressive agents to standard therapy in IgAN, several studies have questioned safety and efficacy of these agents (3)(4)(5). B cell depletion potentially offers a new therapy (5).…”

“…Recently RTX is being increasingly used in various autoimmune diseases (11,12). IgAN is an autoimmune disease, indicating that RTX may be helpful to reduce the deterioration in kidney function (4). There are only few studies available using RTX for the treatment of IgAN from ten years ago (3).…”