A randomized, controlled trial of rituximab in IgA nephropathy with proteinuria and renal dysfunction

Academic Article

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 andeGFR<90ml/minper1.73m2, toreceive standard therapyor rituximab with standard therapy. Primaryoutcome 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.eGFRdidnotchangein eithergroup. Rituximabdidnot alter thelevel of proteinuriacomparedwith 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, rituximabtherapydidnot significantlyimproverenal function or proteinuria assessed over1year. Althoughrituximab 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.
  • Digital Object Identifier (doi)

    Author List

  • Lafayette RA; Canetta PA; Rovin BH; Appel GB; Novak J; Nath KA; Sethi S; Tumlin JA; Mehta K; Hogan M
  • Start Page

  • 1306
  • End Page

  • 1313
  • Volume

  • 28
  • Issue

  • 4