Abstract
Background
Rituximab (RTX) is approved for remission induction in ANCA associated vasculitis (AAV). However, data on use of RTX in patients with severe renal disease is lacking.
Methods
We conducted a retrospective multi-center study to evaluate the efficacy and safety of RTX with glucocorticoids (GC) with and without use of concomitant cyclophosphamide (CYC) for remission induction in patients presenting with e GFR less than 20 ml/min/1.73 m2. We evaluated outcomes of remission at 6 months (6 M), renal recovery after acute dialysis at diagnosis, e-GFR rise at 6 M, patient and renal survival and adverse events.
Results
A total 37 patients met the inclusion criteria. The median age was 61 years. (55–73), 62 % were males, 78 % had new diagnosis and 59 % were MPO ANCA positive. The median (IQR) e-GFR at diagnosis was 13 ml/min/1.73 m2 (7–16) and 15 required acute dialysis. Eleven (30 %) had alveolar hemorrhage. Twelve (32 %) received RTX with GC, 25 (68 %) received RTX with GC and CYC and seventeen (46 %) received plasma exchange. The median (IQR) follow up was 973 (200–1656) days. Thirty two of 33 patients (97 %) achieved remission at 6 M and 10 of 15 patients (67 %) requiring dialysis recovered renal function. The median prednisone dose at 6 M was 6 mg/day. The mean (SD) increase in e-GFR at 6 months was 14.5 (22) ml/min/m2. Twelve patients developed ESRD during follow up. There were 3 deaths in the first 6 months. When stratified by use of concomitant CYC, there were no differences in baseline e GFR, use of plasmapheresis, RTX dosing regimen or median follow up days between the groups. No differences in remission, renal recovery ESRD or death were observed.
Conclusions
This study of AAV patients with severe renal disease demonstrates that the outcomes appear equivalent when treated with RTX and GC with or without concomitant CYC.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Hogan SL, Falk RJ, Chin H, Cai J, Jennette CE, Jennette JC et al (2005) Predictors of relapse and treatment resistance in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis. Ann Intern Med 143(9):621–631
Jayne DR, Gaskin G, Rasmussen N, Abramowicz D, Ferrario F, Guillevin L et al (2007) Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol 18(7):2180–2188
Slot MC, Tervaert JW, Franssen CF, Stegeman CA (2003) Renal survival and prognostic factors in patients with PR3-ANCA associated vasculitis with renal involvement. Kidney Int 63(2):670–677
Mekhail TM, Hoffman GS (2000) Longterm outcome of Wegener’s granulomatosis in patients with renal disease requiring dialysis. J Rheumatol 27(5):1237–1240
Booth AD, Almond MK, Burns A, Ellis P, Gaskin G, Neild GH et al (2003) Outcome of ANCA-associated renal vasculitis: a 5-year retrospective study. Am J Kidney Dis 41(4):776–784
Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD et al (1992) Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med 116(6):488–498
Little MA, Nightingale P, Verburgh CA, Hauser T, De Groot K, Savage C et al (2010) Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis. Ann Rheum Dis 69(6):1036–1043
Geetha D, Kallenberg C, Stone JH, Salama AD, Appel GB, Duna G et al (2015) Current therapy of granulomatosis with polyangiitis and microscopic polyangiitis: the role of rituximab. J Nephrol 28(1):17–27
Alberici F, Jayne DR (2014) Impact of rituximab trials on the treatment of ANCA-associated vasculitis. Nephrol Dial Transplant 29(6):1151–1159. doi:10.1093/ndt/gft318
Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS et al (2010) Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 363(3):221–232
Jones RB, Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA et al (2010) Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 363(3):211–220
Radhakrishnan J, Cattran DC (2012) The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines–application to the individual patient. Kidney Int 82(8):840–856
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130(6):461–470
Gregersen JW, Chaudhry A, Jayne DR (2013) Rituximab for ANCA-associated vasculitis in the setting of severe infection. Scand J Rheumatol 42(3):207–210
de Lind van Wijngaarden RA, Hauer HA, Wolterbeek R, Jayne DR, Gaskin G, Rasmussen N et al (2006) Clinical and histologic determinants of renal outcome in ANCA-associated vasculitis: A prospective analysis of 100 patients with severe renal involvement. J Am Soc Nephrol 17(8):2264–2274
Pepper RJ, Chanouzas D, Tarzi R, Little MA, Casian A, Walsh M et al (2013) Intravenous cyclophosphamide and plasmapheresis in dialysis-dependent ANCA-associated vasculitis. Clin J Am Soc Nephrol 8(2):219–224
Li ZY, Gou SJ, Chen M, Zhao MH (2013) Predictors for outcomes in patients with severe ANCA-associated glomerulonephritis who were dialysis-dependent at presentation: a study of 89 cases in a single Chinese center. Semin Arthritis Rheum 42(5):515–521
Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS et al (2013) Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med 369(5):417–427
Berden AE, Jones RB, Erasmus DD, Walsh M, Noel LH, Ferrario F et al (2012) Tubular lesions predict renal outcome in antineutrophil cytoplasmic antibody-associated glomerulonephritis after rituximab therapy. J Am Soc Nephrol 23(2):313–321
Acknowledgments
Parts of this work were presented at the American Society of Nephrology meeting in Philadelphia, Pennsylvania in November 2014. “This publication was made possible by the Johns Hopkins Institute for Clinical and Translational Research (ICTR) which is funded in part by Grant Number UL1 TR 001079 from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS or NIH.”
Conflict of interest
Duvuru Geetha, M.D., MR.C.P. (U.K.), Consultant for Genentech, Zdenka Hruskova, M.D., PhD: lecture fees/honoraria from GSK and Biogen Idec, Marten Segelmark, M.D.: lecture fees from Roche, Matthew, D. Morgan, MB ChB, MRCP, PhD: none, Jonathan Hogan, M.D.: none, Per Erikson: none, Philip Seo: none, Rebecca Manno: none, Teresa Cavero: none, Jessica Dale: none, Lorraine, Harper, PhD, MRCP: none, Vladimir Tesar, MD, PhD, MBA: fees for lecture and advisory board: Amgen, Abbvie, Baxter, Chemocentryx, Fresenius, GSK. David RW Jayne, M.D., FRCP: Research grant and consulting and lecture fees from Roche/Genentech.
Ethical approval
All procedures performed in studies involving human participants were done in accordance with ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent
The study was approved as an exempt research study by the institutional review board due to the retrospective nature of the study.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Geetha, D., Hruskova, Z., Segelmark, M. et al. Rituximab for treatment of severe renal disease in ANCA associated vasculitis. J Nephrol 29, 195–201 (2016). https://doi.org/10.1007/s40620-015-0208-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40620-015-0208-y