INTRAVENOUS PULSE CYCLOPHOSPHAMIDE TREATMENT OF SEVERE LUPUS NEPHRITIS - A PROSPECTIVE 5-YEAR STUDY

Despite its widespread use, there are only a few published studies of the use of intravenous high dose pulse cyclophosphamide in systemic lu pus nephritis. There are few data about the long-term efficacy and saf ety of this form of therapy. This study evaluates the clinical efficac y, toxicity, and effects on renal morphology of this regimen in patien ts with severe lupus nephritis followed prospectively over a five-year period. Twenty consecutive patients with severe active lupus nephriti s were enrolled in a treatment regimen of six monthly intravenous puls es of cyclophosphamide (0.5 to 1 g/m(2)) together with high dose corti costeroid therapy which was rapidly tapered. Efficacy was assessed by improvement or stabilization of clinical, serologic and renal function al parameters. Repeat renal biopsies were performed in 15 patients. Po tential 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 decreas ed proteinuria in 19/20 patients. Nephrotic syndrome remitted in 8/10 patients by one year. Over five years of follow-up, there were five tr eatment failures defined as a doubling of serum creatinine over baseli ne. At five years, 3 patients required renal replacement therapy. Elev ated 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 treatme nt were, however, more likely to have diffuse proliferative lupus neph ritis (WHO Class IV) lesions on initial biopsy. Toxicity during the in itial 12 months of the study included three serious infections, as wel l as mild alopecia and amenorrhea. No patients had evidence of hemorrh agic cystitis or development of a malignancy in up to 5 years of follo w-up. Repeat renal biopsies at 12 to 18 months from study entry showed resolution of histologic activity but greater chronicity. This regime n effectively induced a remission in the majority of patients with sev ere lupus nephritis. However not all patients responded to this treatm ent and studies of newer regimens to prevent relapses and chronic irre versible changes of renal damage are needed.