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Intermittent intravenous cyclophosphamide therapy for lupus nephritis
T J Lehman1, D D Sherry, L Wagner-Weiner
1Division of Pediatric Rheumatology, Hospital for Special Surgery, New York, NY 10021.
Insights
Intermittent intravenous cyclophosphamide shows promise in treating childhood lupus nephritis, improving key health markers and reducing protein in urine. Further studies are needed to confirm long-term safety and efficacy compared to prednisone alone.
Area of Science:
- Pediatric Nephrology
- Rheumatology
- Immunosuppressive Therapy
Background:
- Childhood lupus nephritis is a serious complication of systemic lupus erythematosus.
- Current treatments, primarily corticosteroids, can have significant side effects or be ineffective.
- Alternative immunosuppressive strategies are needed for severe or refractory cases.
Purpose of the Study:
- To evaluate the safety and efficacy of intermittent intravenous cyclophosphamide in pediatric lupus nephritis.
- To assess treatment outcomes in children with corticosteroid-unresponsive or steroid-intolerant lupus nephritis.
Main Methods:
- A preliminary study involving 16 children (4-18 years) with lupus nephritis.
- Treatment administered monthly for 6 months, then quarterly, with intravenous cyclophosphamide.
- Patients included those with active nephritis unresponsive to corticosteroids or with nephrotic syndrome/side effects.
Main Results:
- Significant improvements observed at 1 year in hemoglobin, C3, and C4 levels (p < 0.005).
- Mean prednisone dosage significantly reduced (p < 0.005).
- Significant decrease in 24-hour urine protein excretion (p < 0.05) and improved creatinine clearance in relevant patients (p < 0.05).
Conclusions:
- Intermittent intravenous cyclophosphamide therapy demonstrated significant short-term efficacy in improving immunological markers and renal function in childhood lupus nephritis.
- The treatment allowed for a reduction in corticosteroid dosage.
- Long-term safety and efficacy require further investigation; current use recommended for severe or refractory cases.
Abstract:
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 less than 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 less than 0.005), despite a significant reduction in mean prednisone dosage (31 +/- 5 to 14 +/- 2 mg/day; p less than 0.005). There was a decrease in 24-hour urine protein excretion from 3121 +/- 913 to 1016 +/- 364 mg/24 hours (p less than 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 less than 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 corticosteroid-resistant and potentially life-threatening disease.