title: Early versus late start of immunosuppressive therapy in idiopathic membranous nephropathy: a randomized controlled trial.
abstract: BACKGROUND
  Immunosuppressive therapy in idiopathic membranous nephropathy (iMN) is debated. Accurate identification of patients at high risk for end-stage renal disease (ESRD) allows early start of therapy in these patients. It is unknown if early start of therapy is more effective and/or less toxic than late start (i.e. when GFR deteriorates).
  
  
  METHODS
  We conducted a randomized open-label study in patients with iMN, a normal renal function and a high risk for ESRD (urinary beta2m >0.5 microg/min, UIgG >125 mg/day). Patients started with immunosuppressive therapy (cyclophosphamide for 12 months, and steroids) either immediately after randomization or when renal function deteriorated (DeltasCr > or =+25% and sCr >135 micromol/l or DeltasCr > or =+50%). End points were remission rates, duration of the nephrotic syndrome (NS), renal function and complications.
  
  
  RESULTS
  The study included 26 patients (24 M/2 F), age 48 +/- 12 years; sCr 96 micromol/l (range 68-126) and median proteinuria 10.0 g/10 mmol Cr. Early treatment resulted in a more rapid onset of remission (P = 0.003) and a shorter duration of the NS (P = 0.009). However, at the end of the follow-up (72 +/- 22 m), there were no differences in overall remission rate, sCr (93 versus 105 micromol/l), proteinuria, relapse rate and adverse events.
  
  
  CONCLUSIONS
  In high-risk patients with iMN, immunosuppressive treatment is effective in inducing a remission. Early treatment shortens the duration of the nephrotic phase, but does not result in better preservation of renal function. Our study indicates that treatment decisions must be based on risk and benefit assessment in the individual patient.
authors: Department of Nephrology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. J.Hofstra@nier.umcn.nl
authors: Julia M
authors: JM
authors: Hofstra
authors: Amanda J W
authors: AJ
authors: Branten
authors: Joris J J M
authors: JJ
authors: Wirtz
authors: Ton C
authors: TC
authors: Noordzij
authors: Peggy W G
authors: PW
authors: du Buf-Vereijken
authors: Jack F M
authors: JF
authors: Wetzels
mesh_terms: D000328:Adult; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012074:Remission Induction; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide