Abstract: FR-PO1012

Podocyte Injury Is a Feature of Transplant Glomerulopathy

Session Information

Category: Transplantation

  • 1701 Transplantation: Basic and Experimental

Authors

  • Moradi, Sara, Boston University , Worcesterr, Massachusetts, United States
  • Chen, Hui, BMC, Boston, Massachusetts, United States
  • Francis, Jean M., Boston University Medical Center, Boston, Massachusetts, United States
  • Henderson, Joel M., Boston University Medical Center, Boston, Massachusetts, United States
Background

Transplant Glomerulopathy (TG) is a chronic progressive glomerular lesion seen in about 20% of human renal allografts at five years post-transplant. TG is primarily a result of endothelial injury and is analogous to the glomerular lesion of thrombotic microangiopathy. Diagnosis of TG is strongly associated with poor long-term graft survival; however there is no effective treatment to prevent the development or progression of TG. Since proteinuria is a key feature of TG, we hypothesize that podocyte injury is associated with its development and progression.

Methods

We examined diagnostic electron micrographs from 21 kidney allograft biopsies (range 1 month to 15 years post-transplant), and scored these images for ultrastructural features of podocyte and endothelial injury. Podocyte injury in the form of foot process (FP) effacement, and endothelial injury in the form of cell swelling and loss of fenestrations, were scored on a 0 to 3 scale corresponding to percentage of capillary loop surface involved by the lesion throughout the biopsy (0=0-10%, 1=10-25%, 2=25-50%, 3=50%+). We also immunostained formalin-fixed, paraffin-embedded sections with primary antibodies against a panel of podocyte-specific proteins, and molecular markers of podocyte injury. Features of podocyte injury were correlated with severity of TG (Banff “cg” score for the biopsy) and endothelial injury.

Results

We found a significant correlation between podocyte injury severity and both “cg” score and endothelial injury severity. FP effacement score increases with increasing cg score; Kruskal-Wallis test reveals that median vary significantly (P<0.05). FP effacement also correlates with endothelial injury; linear regression of these data reveals a significantly non-zero slope (P<0.0001) and R-squared = 0.5673. Immunohistochemical staining suggests loss of differentiating features in podocytes in association with transplant glomerulopathy and endothelial injury.

Conclusion

These findings support the contention that podocyte injury is a common feature of TG, and its severity (and potentially its pathogenesis) is closely tied to extent and severity of the endothelial injury.

Funding

  • Clinical Revenue Support