Treatment with cyclophosphamide delays the progression of chronic lesions more effectively than does treatment with azathioprine plus methylprednisolone in patients with proliferative lupus nephritis

OBJECTIVE: To analyze the effect of treatment with either pulse cyclophosphamide (CYC) or azathioprine (AZA) combined with methylprednisolone (MP), on serial biopsy results in patients with proliferative lupus nephritis, and to evaluate the predictive value of various histopathologic and clinical parameters with regard to disease outcome. METHODS: Biopsy specimens from patients with proliferative lupus nephritis, obtained at study entry and after 2 years of therapy, were scored according to a standardized method, and results assessed in relation to disease outcome. RESULTS: Of the 87 patients originally enrolled, 39 underwent repeat biopsy. These patients were representative of the overall group, both at entry and at 2-year followup. The median activity index changed from 8.0 to 2.7 (no differences between the treatment groups). In the group treated with AZA plus MP (AZA group), the increase in the median chronicity index (from 2.7 to 3.8) was larger than that in the CYC group (from 2.7 to 3.0) (P = 0.050). In multivariate analyses, renal function at enrollment and after 2 years was the best predictor of renal function at the last visit, while none of the histopathologic variables (either at entry or at 2 years) added to this prediction. Comparing patients whose disease transitioned to class II with those who had persistent proliferative lupus nephritis revealed no differences between the treatment groups at either time point, and no clinical differences at 2 years. However, a higher serum creatinine level at entry and greater proteinuria at last visit were characteristic of patients who still had proliferative lupus nephritis at 2 years. CONCLUSION: These results indicate that, although both CYC and AZA are effective in reducing active lesions in lupus nephritis, progression of chronic lesions is more effectively halted by CYC. Variables assessed by repeat biopsy do not predict clinical outcome.