Background: Few studies tried to identify prognostic factors of the renal outcome in SLE patients with lupus nephritis treated with cyclophosphamide (CTX). Objectives: To define histological or clinical parameters capable of predicting a poor response in patients with lupus nephritis. To this aim we evaluated HGF and TGF-beta1 tissue expression in renal specimens and their capacity to predict the renal outcome after CTX therapy. Methods: Sixteen SLE patients (13 F, 3 M; mean ± SD age at renal biopsy 34.2 ± 11.8; mean disease duration 3.3 ± 3.86, mean cumulative dose of CTX treatment 6.2 ± 2.9 g, mean treatment duration 5.4 ± 1.2 months) were studied. Immunohistochemical expression of HGF and TGF-beta1 was examined in tissue samples from kidneys of these patients with nephritis treated with CTX for six months and the results were evaluated following Mizuno score (1). Activity and cronicity indexes were also determined (2). The clinical outcome was evaluated according to criteria to define the nephritic/nephrotic remission(3). Results: Thirteen patients were defined responders and three were non-responders. Lower scores of HGF tubular expression, with higher scores of TGF-beta1 tubular expression and higher cronicity indexes were found in patients non-responders (NR) vs responders (R) (mean ± SD in NR vs R HGF score 1.3 ± 0.6 vs 3.6 ± 0.5 with p=0.0106, TGF score 3.3 ± 0.6 vs 1.1 ± 0.4 with p=0.0106, activity score 12 ± 1.7 vs 7.8 ± 4.3 with p=ns, cronicity index 6.7 ± 1.2 vs 2.1 ± 1.8 with p = 0.0154). No differences between values of proteinuria, creatinine clearance as well as serum complement levels, anti-DNA antibodies between groups were observed. Conclusion: Our findings suggest a predictive value of basal expression levels of renal HGF and TGF-beta1 on the future renal outcome after therapy with CTX at the 6th months follow-up. References: 1. Mizuno S et al. Kidney Int 2001; 59: 1304-14. 2. Austin HA 3rd et al. Kidney Int 1984; 25: 689-95. 3. Boumpas DT et al. Lupus 1998; 7:622-9.
Hepatocyte growth factor (HGF)/transforming growth factor (TGF-BETA1) balance in renal biopsies and clinical outcome in patients with lupus nephritis treated with cyclophosphamide
Gremese E;
2005-01-01
Abstract
Background: Few studies tried to identify prognostic factors of the renal outcome in SLE patients with lupus nephritis treated with cyclophosphamide (CTX). Objectives: To define histological or clinical parameters capable of predicting a poor response in patients with lupus nephritis. To this aim we evaluated HGF and TGF-beta1 tissue expression in renal specimens and their capacity to predict the renal outcome after CTX therapy. Methods: Sixteen SLE patients (13 F, 3 M; mean ± SD age at renal biopsy 34.2 ± 11.8; mean disease duration 3.3 ± 3.86, mean cumulative dose of CTX treatment 6.2 ± 2.9 g, mean treatment duration 5.4 ± 1.2 months) were studied. Immunohistochemical expression of HGF and TGF-beta1 was examined in tissue samples from kidneys of these patients with nephritis treated with CTX for six months and the results were evaluated following Mizuno score (1). Activity and cronicity indexes were also determined (2). The clinical outcome was evaluated according to criteria to define the nephritic/nephrotic remission(3). Results: Thirteen patients were defined responders and three were non-responders. Lower scores of HGF tubular expression, with higher scores of TGF-beta1 tubular expression and higher cronicity indexes were found in patients non-responders (NR) vs responders (R) (mean ± SD in NR vs R HGF score 1.3 ± 0.6 vs 3.6 ± 0.5 with p=0.0106, TGF score 3.3 ± 0.6 vs 1.1 ± 0.4 with p=0.0106, activity score 12 ± 1.7 vs 7.8 ± 4.3 with p=ns, cronicity index 6.7 ± 1.2 vs 2.1 ± 1.8 with p = 0.0154). No differences between values of proteinuria, creatinine clearance as well as serum complement levels, anti-DNA antibodies between groups were observed. Conclusion: Our findings suggest a predictive value of basal expression levels of renal HGF and TGF-beta1 on the future renal outcome after therapy with CTX at the 6th months follow-up. References: 1. Mizuno S et al. Kidney Int 2001; 59: 1304-14. 2. Austin HA 3rd et al. Kidney Int 1984; 25: 689-95. 3. Boumpas DT et al. Lupus 1998; 7:622-9.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
