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Combined intravenous methotrexate and cyclophosphamide for refractory childhood lupus nephritis
  1. T J A Lehman,
  2. B S Edelheit,
  3. K B Onel
  1. Division of Paediatric Rheumatology, Hospital for Special Surgery, and Department of Paediatrics, Sanford Weill Medical College of Cornell University, USA
  1. Correspondence to:
    Dr T J A Lehman MD
    Hospital for Special Surgery, 535 E 70th St, New York, NY 10021, USA;


Objective: To evaluate the efficacy and safety of combining monthly intravenous methotrexate (IV MTX) with monthly IV cyclophosphamide (CYTX; given on the same day) for the treatment of children who develop recurrent diffuse proliferative glomerulonephritis secondary to systemic lupus erythematosus during or after the standard 3 year course of IV CYTX.

Methods: Five children were treated with nine monthly doses of IV CYTX (750–1000 mg/m2/month) and IV MTX (50–300 mg/m2/month) given on the same day. Their clinical and laboratory measurements were collected every other week throughout the nine months.

Results: All children improved dramatically. SLEDAI scores decreased from an average of 13.8 to 4.4, mean (SD) serum creatinine level fell from 100 (60) to 80 (40) µmol/l, and serum albumin rose from 28 (11) g/l to 41 (6) g/l, while the mean (SD) C3 level increased from 0.5 (0.1) g/l to 0.9 (0.4) g/l. Clinical improvement persisted after 4 years’ follow up despite discontinuing MTX and CYTX after 9 months. The average daily dose of corticosteroids has been reduced from 27.6 mg/day at the start of treatment to 12.5 mg/day at follow up.

Conclusion: Combined IV MTX and IV CYTX treatment effectively controls recurrent or refractory lupus nephritis in children with significant disease activity after treatment with IV CYTX alone.

  • systemic lupus erythematosus
  • nephritis
  • treatment
  • paediatrics
  • cyclophosphamide
  • methotrexate
  • ALT, alanine aminotransferase
  • ANA, antinuclear antibodies
  • AST, aspartate aminotransferase
  • BUN, blood urea nitrogen
  • CBC, complete blood count
  • Cr, creatinine
  • CYTX, cyclophosphamide
  • DPGN, diffuse proliferative glomerulonephritis
  • ESR, erythrocyte sedimentation rate
  • IV, intravenous
  • MTX, methotrexate
  • SLE, systemic lupus erythematosus
  • SLEDAI, SLE disease activity index

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