Intravenous pulse cyclophosphamide treatment of severe lupus nephritis: a prospective five-year study
Valeri, A.; Radhakrishnan, J.; Estes, D.; D'Agati, V.; Kopelman, R.; Pernis, A.; Flis, R.; Pirani, C.; Appel, G.B.
Clinical Nephrology 42(2): 71-78
Despite its widespread use, there are only a few published studies of the use of intravenous high dose pulse cyclophosphamide in systemic lupus nephritis. There are few data about the long-term efficacy and safety of this form of therapy. This study evaluates the clinical efficacy, toxicity, and effects on renal morphology of this regimen in patients with severe lupus nephritis followed prospectively over a five-year period. Twenty consecutive patients with severe active lupus nephritis were enrolled in a treatment regimen of six monthly intravenous pulses of cyclophosphamide (0.5 to 1 g/m-2) together with high dose corticosteroid therapy which was rapidly tapered. Efficacy was assessed by improvement or stabilization of clinical, serologic and renal functional parameters. Repeat renal biopsies were performed in 15 patients. Potential toxicity related to therapy was documented. Over the first six months of treatment, this regimen resulted in improvement of clinical activity, lupus serology, stabilization of renal function and decreased proteinuria in 19/20 patients. Nephrotic syndrome remitted in 8/10 patients by one year. Over five years of follow-up, there were five treatment failures defined as a doubling of serum creatinine over baseline. At five years, 3 patients required renal replacement therapy. Elevated plasma creatinine at time of first biopsy, degree of proteinuria, histologic activity and chronicity were not statistically correlated with treatment failure. Patients who failed to respond to this treatment were, however, more likely to have diffuse proliferative lupus nephritis (WHO Class IV) lesions on initial biopsy. Toxicity during the initial 12 months of the study included three serious infections, as well as mild alopecia and amenorrhea. No patients had evidence of hemorrhagic cystitis or development of a malignancy in up to 5 years of follow-up. Repeat renal biopsies at 12 to 18 months from study entry showed resolution of histologic activity but greater chronicity. This regimen effectively induced a remission in the majority of patients with severe lupus nephritis. However, not all patients responded to this treatment and studies of newer regimens to prevent relapses and chronic irreversible changes of renal damage are needed.