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Abstract
Background
Chronic allograft nephropathy (CAN), which causes graft failure, is related to tubular atrophy and interstitial fibrosis. E-cadherin is a well-known epithelial marker and heat shock protein (HSP)-47 is a collagen-specific molecular chaperone that regulates collagen synthesis. Transforming growth factor (TGF)-β1, a profibrotic cytokine, downregulates E-cadherin and induces expression of mesenchymal markers in an in vitro model. C4d expression is considered a poor prognostic marker for graft survival. This study evaluated the relationship between the expression of E-cadherin, HSP47, TGF-β1, and C4d with the prognosis for CAN.
Methods
Between March 1991 and August 2007, we performed renal allograft biopsies on 42 recipients with deteriorating renal function. CAN was diagnosed according to the chronic allograft damage index (Banff classification). Renal allograft biopsies were examined for the expression of E-cadherin, HSP47, TGF-β1, or C4d by immunohistochemistry. The HSP47, TGF-β1, and E-cadherin staining was scored semiquantitatively by analyzing ten different fields of cortical interstitium and tubules. Biopsies with endothelial C4d staining in peritubular capillaries (≥25%) were designated as C4d-positive.
Results
Of 42 recipients, 17 (40.5%) were in the graft survival group (GS) and 25 (59.5%) were in the graft failure group (GF). E-cadherin expression in tubular cells of the GS was much higher than that of the GF (94.1% vs 52%, P=0.04). HSP47 expression in tubular cells and interstitium in the GF was much higher than that in the GS (84% vs 35.3%, P=0.001). TGF-β1 expression in tubular cells and interstitium in the GF was much higher than that in the GS (72% vs 23.5%, P=0.02).
References
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Fig. 1.
E-cadherin expression in Implantation biopsy vs Functioning group (CAN) vs non functioning group (CAN), arrow (high expression), arrow head (low expression) (×100). (A) Implantation biopsy, high expression of E-cadherin. (B) CAN, Functioning group mild loss of expression of E-cadherin. (C) CAN, non functioning group entire loss of expression. Abbreviation: CAN, chronic allograft nephropathy.
Fig. 2.
HSP47 expression in Implantation biopsy vs Functioning group (CAN) vs non functioning group (CAN), arrow (high expression), arrow head (low expression) (×100). (A) Implantation biopsy, no expression of HSP47. (B) CAN, functioning group, low expression in tubule. (C) CAN, non functioning group, high expression in tubule and interstitium. Abbreviations: HSP, heat shock protein; CAN, chronic allograft nephropathy.
Fig. 3.
TGF-ß1 expression in implantation biopsy vs functioning group (CAN) vs non functioning group (CAN), arrow (high expression), arrow head (low expression) (×100). (A) Implantation biopsy, no expression of TGF-ß1. (B) CAN, Functioning group mild expression in interstitium. (C) CAN, non functioning group high expression in tubule & inerstitium. Abbreviations: TGF, transforming growth factor; CAN, chronic allograft nephropathy.
Fig. 4.
Correlation of E-cadherin E-cadherin, HSP-47, TGF-β1, C4d expression and graft survivals after transplantation. (A) E-cadherin.(B) HSP-47. (C) TGF-b1. (D) C4d. Abbreviations: HSP, heat shock protein; TGF, transforming growth factor.
Table 1.
Banff 97 diagnostic categories for renal allograft biopsies-update
Table 2.
Patients characteristics in post-transplant chronic allograft nephropathy
Table 3.
Correlation between Banff score and functioning graft/ graft loss
Table 4.
Correlation between markers and proteinuria, serum creatinine
| Marker | Proteinuria | P | Cr a | P | ||
|---|---|---|---|---|---|---|
| (+) | (−) | |||||
| E-cadherin | (+) | 11 | 2 | 0.96 | 2.75 | 0.40 |
| (−) | 20 | 9 | 3.04 | |||
| HSP47 | (+) | 11 | 16 | 0.019 | 3.05 | 0.477 |
| (−) | 1 | 14 | 2.46 | |||
| TGF-ß1 | (+) | 5 | 20 | 0.136 | 3.10 | 0.380 |
| (−) | 7 | 10 | 2.40 | |||
| C4d | (+) | 3 | 9 | 0.746 | 4.14 | ＜0.05 |
| (−) | 9 | 21 | 2.37 | |||
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