Hepatocyte growth factor and transforming growth factor beta1 ratio at baseline can predict early response to cyclophosphamide in systemic lupus erythematosus nephritis

OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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%.
CONCLUSION: These findings indicate that baseline expression of renal HGF and
TGFbeta1 predicts short-term renal outcome after therapy with CYC and steroids.