title: Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis: lessons from long-term followup of patients in the Euro-Lupus Nephritis Trial.
abstract: OBJECTIVE
  In the Euro-Lupus Nephritis Trial (ELNT), 90 patients with lupus nephritis were randomly assigned to a high-dose intravenous cyclophosphamide (IV CYC) regimen (6 monthly pulses and 2 quarterly pulses with escalating doses) or a low-dose IV CYC regimen (6 pulses of 500 mg given at intervals of 2 weeks), each of which was followed by azathioprine (AZA). After a median followup of 41 months, a difference in efficacy between the 2 regimens was not observed. The present analysis was undertaken to extend the followup and to identify prognostic factors.
  
  
  METHODS
  Renal function was prospectively assessed quarterly in all 90 patients except 5 who were lost to followup. Survival curves were derived using the Kaplan-Meier method.
  
  
  RESULTS
  After a median followup of 73 months, there was no significant difference in the cumulative probability of end-stage renal disease or doubling of the serum creatinine level in patients who received the low-dose IV CYC regimen versus those who received the high-dose regimen. At long-term followup, 18 patients (8 receiving low-dose and 10 receiving high-dose treatment) had developed permanent renal impairment and were classified as having poor long-term renal outcome. We demonstrated by multivariate analysis that early response to therapy at 6 months (defined as a decrease in serum creatinine level and proteinuria <1 g/24 hours) was the best predictor of good long-term renal outcome.
  
  
  CONCLUSIONS
  Long-term followup of patients from the ELNT confirms that, in lupus nephritis, a remission-inducing regimen of low-dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high-dose regimen. Early response to therapy is predictive of good long-term renal outcome.
authors.affiliation: Université Catholique de Louvain, Brussels, Belgium. houssiau@ruma.ucl.ac.be
authors.forename: Frédéric A
authors.initials: FA
authors.lastname: Houssiau
authors.forename: Carlos
authors.initials: C
authors.lastname: Vasconcelos
authors.forename: David
authors.initials: D
authors.lastname: D'Cruz
authors.forename: Gian Domenico
authors.initials: GD
authors.lastname: Sebastiani
authors.forename: Enrique
authors.initials: E
authors.lastname: de Ramon Garrido
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Danieli
authors.forename: Daniel
authors.initials: D
authors.lastname: Abramovicz
authors.forename: Daniel
authors.initials: D
authors.lastname: Blockmans
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mathieu
authors.forename: Haner
authors.initials: H
authors.lastname: Direskeneli
authors.forename: Mauro
authors.initials: M
authors.lastname: Galeazzi
authors.forename: Ahmet
authors.initials: A
authors.lastname: Gül
authors.forename: Yair
authors.initials: Y
authors.lastname: Levy
authors.forename: Peter
authors.initials: P
authors.lastname: Petera
authors.forename: Rajko
authors.initials: R
authors.lastname: Popovic
authors.forename: Radmila
authors.initials: R
authors.lastname: Petrovic
authors.forename: Renato Alberto
authors.initials: RA
authors.lastname: Sinico
authors.forename: Roberto
authors.initials: R
authors.lastname: Cattaneo
authors.forename: Josep
authors.initials: J
authors.lastname: Font
authors.forename: Geneviève
authors.initials: G
authors.lastname: Depresseux
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cosyns
authors.forename: Ricard
authors.initials: R
authors.lastname: Cervera
mesh_terms: D000293:Adolescent; D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007275:Injections, Intravenous; D007677:Kidney Function Tests; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D011507:Proteinuria / Q000188:drug therapy; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D001379:Azathioprine