Therapy of Lupus Nephritis

We evaluated renal function in 107 patients with active lupus nephritis who participated in long-term randomized therapeutic trials (median follow-up, seven years). For patients taking oral prednisone alone, the probability of renal failure began to increase substantially after five years of observation. Renal function was better preserved in patients who received various cytotoxic-drug therapies, but the difference was statistically significant only for intravenous cyclophosphamide plus low-dose prednisone as compared with high-dose prednisone alone (P = 0.027). The advantage of treatment with intravenous cyclophosphamide over oral prednisone alone was particularly apparent in the high-risk subgroup of patients who had chronic histologic changes on renal biopsy at study entry. Patients treated with intravenous cyclophosphamide have not experienced hemorrhagic cystitis, cancer, or a disproportionate number of major infections. We conclude that, as compared with high-dose oral prednisone alone, treatment of lupus glomerulonephritis with intravenous cyclophosphamide reduces the risk of end-stage renal failure with few serious complications. (N Engl J Med 1986;314:614–9.) The potential for adverse outcomes associated with lupus nephritis and its treatment has prompted a number of controlled trials to refine therapeutic approaches to this disorder. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 These efforts have been hampered by an incomplete understanding of the cause of systemic lupus erythematosus, concern about the toxic effects of the regimens under investigation, the heterogeneity of disease among study populations, and the unpredictable but often slow accrual of major clinical failure outcomes, such as end-stage renal disease or death. Two recent approaches have attempted to circumvent the need for long-term follow-up of large patient groups in order to determine the efficacy . . .