Hepatocyte growth factor and transforming growth factor β1 ratio at baseline can predict early response to cyclophosphamide in systemic lupus erythematosus nephritis

Abstract

To determine whether the ratio of hepatocyte growth factor (HGF) to transforming growth factor beta1 (TGFbeta1) in systemic lupus erythematosus (SLE) nephritis could be a prognostic factor for response to therapy with cyclophosphamide (CYC) and steroids at 6 months, and to examine whether the molecular ratio of HGF to TGFbeta1 correlates with the activity index (AI) and chronicity index (CI) and has predictive value for remission at the sixth month. Thirty-six SLE patients with new-onset nephritis, 25 of whom were treated with CYC and steroids, entered into a prospective observational cohort trial at a tertiary university referral center. Renal biopsy findings and clinical parameters were recorded for all patients. Histopathologic, clinical, and immunohistochemical data at baseline served to define the predictive value for the outcome at 6 months. AI and CI at baseline did not distinguish patients who had achieved remission from those who had not achieved remission after receiving CYC plus steroids. HGF and TGFbeta1 were expressed in the tubuli, not in the glomeruli. The CI correlated directly with the TGFbeta1 extension score (TGFbeta1-ES) (r = 0.43, P = 0.008), but correlated indirectly with the HGF intensity score (HGF-IS) (r = -0.39, P = 0.02) and the HGF-ES (r = -0.45, P = 0.006). An HGF-ES:TGFbeta1-ES ratio of >or=1 at baseline distinguished patients who had achieved remission from those who had not achieved remission, with a predictive value of 94%. These findings indicate that baseline expression of renal HGF and TGFbeta1 predicts short-term renal outcome after therapy with CYC and steroids.