title: Clinical, biochemical and pathological predictors of poor response to intravenous cyclophosphamide in patients with proliferative lupus nephritis.
abstract: BACKGROUND
  Reports in the literature on the outcome of lupus nephritis (LN) treated with intravenous (i.v.) cyclophosphamide have varied considerably. Previous studies have suggested that less than 25% of patients with LN will progress to end stage renal failure (ESRD) after 5 years. In addition it has been reported that serum creatinine and chronic histologic changes on kidney biopsy are useful markers of renal prognosis. Whether treatment with cyclophosphamide alters the predictive value of these markers in LN patients is not clear. The aim of this study was to review our experience of treating a large cohort of patients with LN treated with i.v. cyclophosphamide and to identify biochemical and histological features at the time renal biopsy which predict outcome in these patients.
  
  
  METHODS
  We retrospectively reviewed our experience with 43 consecutive patients who met criteria for either World Health Organization (WHO) classification III (focal proliferative) or IV (diffuse proliferative) LN and were treated with monthly i.v. cyclophosphamide. Biochemical indices of renal function and lupus disease activity were recorded. Renal biopsies, performed within two months of commencing therapy, were reviewed by two experienced pathologists and classified according to WHO classification as well as activity and chronicity index. The primary outcome variable for the analysis was the development of ESRD.
  
  
  RESULTS
  Patients were followed for a mean of 2 years after renal biopsy. The mean dose of cyclophosphamide received by patients was 8.3 g. One patient died during follow up and 22 (51%) progressed to ESRD. A higher serum creatinine (p = 0.003) and higher score for interstitial fibrosis (p = 0.001) were associated with shorter renal survival. There was no significant association between activity index or its components or in the total chronicity score and survival free from the need for dialysis.
  
  
  CONCLUSIONS
  In our experience more than half of patients treated with i.v. cyclophosphamide for LN progress to ESRD and a high serum Cr and a high degree of interstitial fibrosis on renal biopsy before treatment are associated with a worse renal prognosis.
authors.affiliation: Division of Nephrology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Conlon
authors.forename: C A
authors.initials: CA
authors.lastname: Fischer
authors.forename: M C
authors.initials: MC
authors.lastname: Levesque
authors.forename: S R
authors.initials: SR
authors.lastname: Smith
authors.forename: E W
authors.initials: EW
authors.lastname: St Clair
authors.forename: N B
authors.initials: NB
authors.lastname: Allen
authors.forename: J A
authors.initials: JA
authors.lastname: Fleming
authors.forename: D N
authors.initials: DN
authors.lastname: Howell
mesh_terms: D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000517:prevention & control; D008181:Lupus Nephritis / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D003520:Cyclophosphamide