title: Long-term follow-up of a randomised controlled trial of azathioprine/methylprednisolone versus cyclophosphamide in patients with proliferative lupus nephritis.
abstract: OBJECTIVE
  The objectives of this study are to analyse the long-term follow-up of a randomised controlled trial of induction treatment with azathioprine/methylprednisolone (AZA/MP) versus high-dose intravenous cyclophosphamide (ivCY) in patients with proliferative lupus nephritis (LN) and to evaluate the predictive value of clinical, laboratory and renal biopsy parameters regarding renal outcome.
  
  
  METHODS
  87 patients with biopsy-proven proliferative LN were treated with either AZA/MP (n=37) or ivCY (n=50), both with oral prednisone. After 2 years, renal biopsy was repeated, and all patients continued with AZA/oral prednisone. The primary study end point was sustained doubling of serum creatinine. Secondary end points included renal relapse, end-stage renal disease and mortality.
  
  
  RESULTS
  After a median follow-up of 9.6 years, no significant differences between AZA/MP versus ivCY groups were found in the proportion of patients with sustained doubling of serum creatinine (n=6 (16%) vs n=4 (8%); p=0.313), end-stage renal disease (n=2 (5%) vs n=2 (4%); p=1.000) or mortality (n=6 (16%) vs n=5 (10%); p=0.388). Renal relapses occurred more often in the AZA/MP group (n=14 (38%) vs n=5 (10%); p=0.002, HR: 4.5). Serum creatinine, proteinuria and immunosuppressive treatment regimens at the last follow-up were comparable. Clinical and laboratory parameters at baseline and after 2 years, and renal biopsy parameters (only) at baseline predicted renal outcome.
  
  
  CONCLUSIONS
  Induction treatment with ivCY was superior to AZA/MP in preventing renal relapses, but other parameters for renal function did not differ. AZA/MP can therefore serve as an alternative in patients with proliferative LN who wish to avoid gonadal toxicity of CY. Several prognostic factors of long-term renal outcome were identified.
authors: Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. s.arends@reuma.umcg.nl
authors: Suzanne
authors: S
authors: Arends
authors: Cecile
authors: C
authors: Grootscholten
authors: Ronald H W M
authors: RH
authors: Derksen
authors: Stefan P
authors: SP
authors: Berger
authors: Ruud G L
authors: RG
authors: de Sévaux
authors: Alexandre E
authors: AE
authors: Voskuyl
authors: Marc
authors: M
authors: Bijl
authors: Jo H M
authors: JH
authors: Berden
mesh_terms: D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001379:Azathioprine / Q000008:administration & dosage*; D003404:Creatinine / Q000097:blood; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007676:Kidney Failure, Chronic / Q000401:mortality / Q000517:prevention & control; D008181:Lupus Nephritis / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D011379:Prognosis; D011507:Proteinuria / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D003404:Creatinine; D001379:Azathioprine; D008775:Methylprednisolone