title: Rituximab for treatment of severe renal disease in ANCA associated vasculitis.
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 m(2). 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 m(2) (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/m(2). 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.
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD, USA. gduvura@jhmi.edu.|Johns Hopkins Bayview Medical Center, Johns Hopkins University, Baltimore, MD, 21224, USA. gduvura@jhmi.edu.
authors.forename: Duvuru
authors.initials: D
authors.lastname: Geetha
authors.affiliation: Department of Nephrology, Charles University, Prague, Czech Republic.
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Hruskova
authors.affiliation: Department of Medicine, Linkoping University, Linkoping, Sweden.
authors.forename: Marten
authors.initials: M
authors.lastname: Segelmark
authors.affiliation: Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hogan
authors.affiliation: University of Birmingham, Birmingham, UK.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Morgan
authors.affiliation: Hospital 12 de Octubre in Madrid, Madrid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Cavero
authors.affiliation: Department of Rheumatology, Linköping University, Linköping, Sweden.|Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Seo
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Manno
authors.affiliation: School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Jessica
authors.initials: J
authors.lastname: Dale
authors.affiliation: University of Birmingham, Birmingham, UK.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Harper
authors.affiliation: Department of Nephrology, Charles University, Prague, Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tesar
authors.affiliation: Addenbrooke's Hospital, Cambridge, UK.
authors.forename: David Rw
authors.initials: DR
authors.lastname: Jayne
mesh_terms: D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005921:Glomerulonephritis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000276:immunology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D010951:Plasma Exchange; D020127:Recovery of Function; D012074:Remission Induction; D006435:Renal Dialysis; D012189:Retrospective Studies; D000069283:Rituximab / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D000069283:Rituximab; D003520:Cyclophosphamide
keywords: ANCA vasculitis; Renal disease; Rituximab