Abstract: TH-PO1003

High-Resolution Digital Analysis of Leukocyte Densities in Early Surveillance Biopsies Significantly Improves Prediction of Kidney Transplant Function after Four Years of Follow-Up

Session Information

Category: Transplantation

  • 1702 Transplantation: Clinical and Translational

Authors

  • Von Vietinghoff, Sibylle, Hannover Medical School, Hannover, Germany
  • Braesen, Jan H., Medizinische Hochschule Hannover, Hannover, Germany
  • Khalifa, Abedalrazag Ahmad, Medizinische Hochschule Hannover, Hannover, Germany
  • Schmitz, Jessica, Hannover Medical School, Hannover, Germany
  • Einecke, Gunilla, Medical School Hannover, Hannover, Germany
  • Schmidt, Bernhard M.W., Hannover Medical School, Hannover, Germany
  • Schwarz, Anke, Hannover Medical School, Hannover, Germany
  • Kreipe, Hans Heinrich, Hannover Medical School, Hannover, Germany
  • Haller, Hermann G., Hannover Medical School, Hannover, Germany
Background

Minor histopathological changes are difficult to quantify by eye. The impact of inflammation on renal allograft survival has been demonstrated in grafts with rejection, and, on a molecular level, also in early surveillance biopsies. We assessed leukocyte abundance in early surveillance biopsies by digital image analysis and analyzed impact on outcome.

Methods

In 67 surveillance biopsies six weeks after transplantation a full Banff classification was performed. T cell (CD3), B cell (CD20), macrophage (CD68) and dendritic cell (CD209) densities and CD206 and HLA-DR markers were assessed by digital image analysis (Definiens system).

Results

An average surface area of 4.7±2.4 mm2 renal cortex was assessed, with average 1.7%CD3, 0.5%CD20, 0.3%CD68, 0.2% CD209. CD3, CD20 and CD68% were significantly higher in grafts with histological rejection. High CD68 density associated with lower combined patient and graft survival after four years. CD20 and CD68 densities inversely correlated with eGFR. CD68 correlated with eGFR loss. CD68+ macrophages were localized mainly in the interstitium. Tubular macrophages increased in grafts with rejection. HLA-DR and CD206 were assessed for M1 and M2 polarization with more M1 positivity in the cortex, and more M2 in the medulla. Among histological measurements including a complete Banff classification, only CD68 density was a significant predictor of CKD IV after four years. It also significantly contributed to the best eGFR prediction set in multivariable linear regression analysis of clinical and pathological parameters. The original CD68 median maintained its discriminative power for survival and eGFR in a second independent cohort.

Conclusion

In comparison to other histopathological markers and as an addition to known clinical risk factors, CD68+ macrophage density measurement significantly improves prognostic value of early surveillance biopsies.

Funding

  • Government Support - Non-U.S.