title: Predictors of treatment outcomes in ANCA-associated vasculitis with severe kidney failure.
abstract: OBJECTIVE
  In ANCA-associated GN, severe renal dysfunction portends a poor prognosis for renal recovery and patient survival. This study evaluated the prognostic factors affecting renal and patient outcomes in patients presenting with severe kidney failure to guide immunosuppressive therapy.
  
  
  METHODS
  This study retrospectively evaluated clinical and histopathologic characteristics of 155 patients who underwent biopsy between October 1985 and February 2011 (median eGFR at presentation, 7.1 ml/min per 1.73 m(2); 87% required hemodialysis), all treated with immunosuppressive medications. Three outcomes of interest were measured: patient survival, renal survival, and treatment response (defined as dialysis-free survival without active vasculitis by 4 months after biopsy). Competing risk, Cox, and logistic regression analyses were conducted for each outcome measure.
  
  
  RESULTS
  Within 4 months after biopsy, treatment response was attained in 51% of patients, 35% remained on dialysis, and 14% died. In a competing risk analysis, estimated cumulative incidence rates of ESRD and disease-related mortality were 26% and 17% at 1 year and 32% and 28% at 5 years, respectively. Cyclophosphamide therapy and treatment response by 4 months were independently associated with patient and renal survival, adjusting for the percentage of normal glomeruli, histopathologic chronicity index score, and baseline clinical characteristics. Only 5% of patients still dialysis dependent at 4 months subsequently recovered renal function. Low chronicity index score (odds ratio [OR], 1.16; 95% confidence interval [95% CI], 1.04 to 1.30, per unit decrease) and baseline eGFR>10 ml/min per 1.73 m(2) (OR, 2.77; 95% CI, 1.09 to 7.01) were significantly associated with treatment response by 4 months. Among cyclophosphamide-treated patients, the likelihood of treatment response was >14% even with highest chronicity index score and eGFR<10 ml/min per 1.73 m(2).
  
  
  CONCLUSIONS
  Although low baseline renal function and severe renal scarring are associated with lower treatment response rate, no "futility" threshold could be identified. Conversely, continued immunosuppressive therapy beyond 4 months is unlikely to benefit patients who remain dialysis dependent.
authors.affiliation: UNC Kidney Center,, ‡Department of Pathology and Laboratory Medicine, and, §Department of Biostatistics, Gillings School of Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina;, †Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea, ‖Nephrology and Transplantation Center, Laiko Hospital, Athens, Greece.
authors.forename: Taewoo
authors.initials: T
authors.lastname: Lee
authors.forename: Adil
authors.initials: A
authors.lastname: Gasim
authors.forename: Vimal K
authors.initials: VK
authors.lastname: Derebail
authors.forename: Yunro
authors.initials: Y
authors.lastname: Chung
authors.forename: JulieAnne G
authors.initials: JG
authors.lastname: McGregor
authors.forename: Sophia
authors.initials: S
authors.lastname: Lionaki
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Poulton
authors.forename: Susan L
authors.initials: SL
authors.lastname: Hogan
authors.forename: J Charles
authors.initials: JC
authors.lastname: Jennette
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Falk
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Nachman
mesh_terms: D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000150:complications / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D058625:End Stage Liver Disease / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy; D005260:Female; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide
keywords: ANCA; glomerulonephritis; vasculitis