Prognostic Factors in Lupus nephritis Treated with Cyclophosphamide Pulses

Abstract

Dear Sir, Intravenous cyclophosphamide (CPA) pulse-therapy is one of the best methods for the lupus nephritis (LN) treatment [1]. Possible severe complications considered that this treatment should be applied only to patients with a high likelihood of success. Thus, prediction of response to therapy ob tains considerable significance. The data from renal biopsy, activity (AI) and chronicity (Cl) indices, together with certain clinical signs, were found to be prognostic markers in LN patients treated with immunosuppres sants [1,2], but the predictive value of these signs was not supported by other studies (3,4]. We tried to determine the best predictors among different clinical and morphological variables using a stepwise multiple linear re gression analysis of the CPA pulse therapy results.Thirty-four patients with severe LN (fe male 32, male 2, nephrotic syndrome in 31, high blood pressure in 23, elevated serum creatinine (Scr) in 15) were treated with CPA pulses (10-20 mg/kg body weight i.v. every 3-4 weeks) combined with high-or middledose prednisolone; total CPA dose was 3-20 g. Renal biopsy performed in 21 patients revealed diffuse proliferative LN (DPLN) in 13, focal proliferative LN (FPLN) in 2, mem branous gonadotropin (GN) in 3 and scle rosing G N in 3 patients. For further anal ysis of morphological data biopsis were di vided in 3 groups according to the degree of severity: membranous GN 1st degree, D PL N /FPL N 2nd degree, sclerosing GN 3rd degree, and semiquantitative AI and Cl [1] were scored. Patients were followed for 3-45 months (mean 15.6). The outcomethe rate of renal functional deteriorationwas calculated a s:(1/Scr0-1/Scrl)/T, where ScrO and Scrl were the Scr levels before treatment and at the end of the follow up period, respectively, and T was the dura tion of follow-up (months).By the end of the follow-up period posi tive results were noted in 72% of patients (remission in 19, improvement in 5), negative results in 28% (deterioration in 1, uremia in 4, death in 5). The results were positive in all 3 patients with membranous GN and in 11 pa tients with D PLN /FPLN ; the results were negative in all 3 patients with sclerosing GN and in 4 with DPLN/FPLN.The prognostic value of clinical and mor phological signs was evaluated by comparing three statistical models which related the prognostic variables to the outcome with multiple linear regression. The first model included eight clinical variables: sex, age, LN duration, duration of exacerbation, Scr level, the presence of high blood pressure and he maturia, and total CPA dose; according to the stepwise multiple regression procedure two of them, LN duration and the Scr level, were chosen as forming the most powerful prog nostic clinical model (model 1, table 1), the predictive power of which was 87.6% (R2 x 100%). At the second stage one morpho logical variable (the degree of histological lesions severity) was added to the eight clini cal variables. The degree of histological se verity and the Scr level were chosen from this set by stepwise re...