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

Richard A. Lafayette, Pietro A. Canetta, Brad H. Rovin, Gerald B. Appel, Jan Novak, Karl A. Nath, Sanjeev Sethi, James A. Tumlin, Kshama Mehta, Marie Hogan, Stephen Erickson, Bruce A. Julian, Nelson Leung, Felicity T. Enders, Rhubell Brown, Barbora Knoppova, Stacy Hall, Fernando C. Fervenza

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56 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1306-1313
Number of pages8
JournalJournal of the American Society of Nephrology
Volume28
Issue number4
DOIs
StatePublished - Apr 2017

ASJC Scopus subject areas

  • Nephrology

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    Lafayette, R. A., Canetta, P. A., Rovin, B. H., Appel, G. B., Novak, J., Nath, K. A., Sethi, S., Tumlin, J. A., Mehta, K., Hogan, M., Erickson, S., Julian, B. A., Leung, N., Enders, F. T., Brown, R., Knoppova, B., Hall, S., & Fervenza, F. C. (2017). A randomized, controlled trial of rituximab in IgA nephropathy with proteinuria and renal dysfunction. Journal of the American Society of Nephrology, 28(4), 1306-1313. https://doi.org/10.1681/ASN.2016060640