Treatment of severe lupus nephritis

effect of prolonged and intermittent intravenous cyclophosphamide

Abstract

OBJECTIVE: Intravenous cyclophosphamide is widely used in the treatment of lupus nephritis. In order to analyze long-term outcome in patients with severe lupus nephritis, we studied 54 patients treated with cyclophosphamide at our services between 1989 and 1999.

MATERIALS AND METHODS: Our study included 42 patients. According to World Health Organization classification, the initial renal biopsy indicated lupus nephritis class III in 16.7% patients and class IV in 83.3%. The average serum creatinine and proteinuria at the beginning of treatment were, respectively 3.1 ± 2.5 mg/dl and 7.2 ± 5.4 g/24h/1.73m2. Eighty-eight percent of patients had nephrotic range proteinuria and 83.3% had serum creatinine levels higher than 1.2mg/dl. The mean duration of nephritis before treatment was 10 months; however, in 52% of patients it was less than 6 months. Average follow-up time from the beginning of treatment to outcome (end-stage renal disease or death) was 72.2 ± 36.3 months. Patients received immunosuppressive therapy according to the National Institutes of Health protocol and were classified, according to clinical and laboratory response into complete remission, partial remission, or treatment failure.

RESULTS: Total or partial remission was achieved in 70% of patients by the end of the first year; 62.5 % of patients were kept in remission up to the third year. The 3, 5, and 10-year actuarial renal survival rates were of 90.2%, 90.2%, and 77.67%, respectively. One patient died and 5 had to start hemodialysis. The adverse effects of immunosuppression were respiratory infection (19.0%), Herpes Zoster (7.1%), temporary (9.5%) and permanent (2.3%) amenorrhea, avascular necrosis of the femoral head (4.7%), and sepsis (2.3%). Neither hemorrhagic cystitis nor neoplasia were observed during follow-up.

CONCLUSIONS: We concluded that intravenous cyclophosphamide was effective in the control of acute lupus nephritis and in the maintenance of long-term renal function without serious adverse events.