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Abstract: PO1393

TGF-β1/Smad Signaling in Glomerulonephritis and Its Association with Progression to CKD

Session Information

Category: Glomerular Diseases

  • 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix

Authors

  • Chalkia, Aglaia, Nephrology Department, Hippokration General Hospital, Athens, Greece
  • Gakiopoulou, Harikleia, 1st Department of Pathology, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
  • Giannou, Panagiota E., Nephrology Department, Hippokration General Hospital, Athens, Greece
  • Alexakou, Zoe, Nephrology Department, Hippokration General Hospital, Athens, Greece
  • Kapota, Athanasia, Nephrology Department, Hippokration General Hospital, Athens, Greece
  • Kourniotis, Dimitris, Nephrology Department, Hippokration General Hospital, Athens, Greece
  • Petras, Dimitrios I., Nephrology Department, Hippokration General Hospital, Athens, Greece
Background

Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine, with diverse roles in fibrosis and inflammation, which acts through Smad signaling in renal pathology. We intended to investigate the expression of TGF-β/Smad signaling in glomerulonephritis (GN) and to assess its role as risk factor for progression to chronic kidney disease (CKD).

Methods

We evaluated the immunohistochemical expression of TGF-β1, phosphorylated Smad3 (pSmad3) and Smad7 semi-quantitatively and quantitatively (computerized image analysis program has also been used) in different compartments of 50 renal biopsies with GN and the results were statistically analyzed with clinicopathological parameters. We also examined the associations among their expressions, the impact of their co-expression, and their role in progression to CKD.

Results

TGF-β1 expression correlated positively with segmental glomerulosclerosis (p=0.025) and creatinine level at diagnosis (p=0.002), while pSmad3 expression with interstitial inflammation (p=0.024). In glomerulus, concomitant expressions of high Smad7 and medium pSmad3 were observed to be correlated with renal inflammation, such as cellular crescent (p=0.011), intense interstitial inflammation (p=0.029) and lower serum complement 3 (p=0.028) and complement 4 (p=0.029). We also reported a significant association between pSmad3 expression in glomerular endothelial cells of proliferative GN (p=0.045) and in podocytes of non-proliferative GN (p=0.005). Finally, on multivariate Cox-regression analysis, TGF-β1 expression (HR= 6.078; 95%CI 1.168-31.627; p=0.032) was emerged as independent predictor for CKD.

Conclusion

TGF-β1/Smad signaling is upregulated with specific characteristics in different forms of GN. TGF-β1 expression is indicated as independent risk factor for progression to CKD, while specific co-expression pattern of pSmad3 and Smad7 in glomerulus is correlated with renal inflammation.