Pulse cyclophosphamide in Lupus Nephritis.


Abstract: The prognosis of Lupus Nephritis has dramatically changed since the introduction of cytotoxic drugs in their treatment. Different protocols have been proposed to reach this goal. Pulse cyclophos­phamide (PCP) was first introduced in the treatment of Systemic Lupus Erythematosus by Sessoms & Kovarsky in 1984. Austin and Colleagues demonstrated it's superiority upon other regimens in Lupus Nephritis in 1986. Pulse Cyclophosphamide is now a well established method for the treatment of lupus nephritis. Pulse Cyclophosphamide tend to produce better results and less side effects, than oral cytotoxic drugs. We have used this method in our SLE patients with lupus nephritis since 1986. We present here, our experience in 84 patients. All patients had a WHO type 1V histological lesions, on light microscopy. Cyclophosphamide was given as 1000 mg per square meter of body surface. ­Pulses were repeated every month until the achievement of a satisfactory result. Then the gap between pulses was increased to 2 and then to 3 months. If a patient was considered in complete remission PCP was discontinued. In case of a recurrence of urinary symptoms, mainly proteinuria, Pulse CycloPhosphamide was started again. Prednisolone was administered, concomitantly and per os, as ½ mg per kilogram of body weight. Prednisolone was also tapered gradually upon the achievement of a satisfactory result. Proteinuria, hematuria, leucocyturia, casts, BUN, creatinine, and blood pressure were measured before starting PCP and after each one. The first and the last measurement were compared to each other by the Student paired t test. Results were also evaluated individually to es­tablish the percentage of their improvement, stabilization, or ag­gravation. The Confidence Interval, a statistical approach to results, is gaining actually more and more adherents. The British MedicaI Jour­nal and its satellites requires such calculations. The Confidence In­terval was calculated for our results, but for those who are not familiar with this statistical approach and for the simplicity of our presentation, we do not present them today. The data are available and will be given upon request. RESULTS: Our patients received a total of 702 pulses. The mean pulses per patient was 8.4. The mean follow up time was 20 months. Proteinuria was improved in 87% of patients, and aggravated in 13% of them. The mean proteinuria decreased from 2399 mg before PCP to 843 mg after the last one, with a p value inferior to 0.000001. Homaturis was improved in 84% of patients. The mean RBC per micro­scopic field was reduced from 17.2 to 4.5 with a p value inferior to 0.000001. Leucocyturia improved in 67% of patients. The mean WBC per microscopic field decreased from 13.8 to 6.8 with a p value inferior to 0.0003. Casts improved in 89% of patients. The mean cast per microscopic field decreased from 3.6 to 0.3 with a p value inferior to 0.000001. Creatinine improved in 75% of patients. The mean serum creatinine decreased from 1.7 to 1.1 with a p value inferior to 0.004. The changes in abnormal BUN and blood pressure were not statistically significant. Side effects were minor: Nausea and vomiting, and mild hair loss in some patients. Particularly we did not observed any hemorrhagic cyc­titis or sever bone marrow depression. We also did not observed any malignancies in our patients. As seen by our results, Pulse Cyclophosphamide gives satisfactory results in Lupus Nephritis. Although some authors do not yet believe in its efficacy and tend to explain the good results by the con comitant use of corticosteroids, it is doubtful that all the benefice be due to them. Austin and colleagues have demonstrated the high supe riority of Pulse Cyclophosphamide upon Corticosteroids alone. To see how much steroids are responsible for the efficacy of Pulse Cyclophos phamide we have started 1 year ago a randomized study with different steroid regimens in Pulse Cyclophosphamide. It is to soon to have a conclusion for the time, but it seems than lower doses of steroids, such as a quarter mg of prednisolone per kilogram of body weight along with pulse Cyclophosphamide may give as good results as higher doses. These observations also tend to demonstrate that the major benefit from Pulse Cyclophosphamide associated to corticosteroids come mainly from cyclophosphamide than steroids. In conclusion, PCP is a good method for the treatment of Lupus Nephritis. Apart the good percentage of improvement and the low in­cidence of side effects, another advantage of this method is the patients compliance. This is the only method ensuring the physician that a patient had correctly followed the treatment regimen.