Intermittent intravenous cyclophosphamide therapy for lupus nephritis

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We carried out a preliminary study to determine whether intermittent intravenous cyclophosphamide therapy could be safely and effectively used in the treatment of childhood lupus nephritis. Sixteen children (4 to 18 years of age) with lupus nephritis were treated with cyclophosphamide monthly for 6 months and then every 3 months. Eight children were treated because of corticosteroid-unresponsive active lupus nephritis, with a fall in their creatinine clearance to <100 ml/min/1.75 m2, and eight children were treated because of corticosteroid-dependent nephrotic syndrome or active lupus nephritis with unacceptable corticosteroid-induced side effects. Cyclophosphamide treatment was associated with significant improvement at 1 year in mean levels of hemoglobin (11.3±0.5 to 13.1±0.3 gm/dl), C3 (52±5.9 to 108±13.7 mg/dl), and C4 (7.6±0.9 to 15.9±2.2 mg/dl) (all p<0.005), despite a significant reduction in mean prednisone dosage (31±5 to 14±2 mg/day; p<0.005). There was a decrease in 24-hour urine protein excretion from 3121±913 to 1016±364 mg/24 hours (p<0.05). For children whose initial creatinine clearance was less than 100 ml/min/1.75 m2, creatinine clearance also improved significantly (57.5±11 to 121±24.5 ml/min/1.75 m2; p<0.05). The long-term safety of intravenous cyclophosphamide therapy and its long-term efficacy in comparison with prednisone alone remain to be established. In the interim, intravenous cyclophosphamide therapy should be reserved for children with severe, unacceptable corticosteroid side effects or with corticosterold-resistant and potentially life-threatening disease.

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