Abstract: FR-PO102

Distinct Morphological Features of Acute Tubular Injury in Renal Allografts Correlate with Clinical Outcome

Session Information

Category: Acute Kidney Injury

  • 003 AKI: Clinical and Translational

Authors

  • Schumann-Bischoff, Andrea, Hannover Medical School, Hannover, Germany
  • Schmitz, Jessica, Hannover Medical School, Hannover, Germany
  • Scheffner, Irina, Medical School Hannover, Nephrology, Hannover, Germany
  • Schmitt, Roland, Medizinische Hochschule Hannover, Hannover, NI, Germany
  • Broecker, Verena, Sahlgrenska University Hospital, Gothenburg, Sweden
  • Haller, Hermann G., Hannover Medical School, Hannover, Germany
  • Braesen, Jan H., Medizinische Hochschule Hannover, Hannover, NI, Germany
  • Gwinner, Wilfried, Hannover Medical School, Hannover, Germany
Background

Acute tubular injury (ATI) is common in renal allografts and is related to inferior long-term allograft function. However, it is unknown which of the morphological features of ATI can predict outcome and how they should be graded. Here, we examine features of ATI systematically in protocol biopsies and biopsies for cause to define the most predictive features for allograft outcome.

Methods

Analyses included 521 protocol biopsies taken at 6 weeks, 3 and 6 months after transplantation and 141 biopsies for cause from 204 patients. Features of ATI included brush border loss, tubular epithelial lucency, flattening, pyknosis, nuclei loss and luminal debris, each graded semi-quantitatively. Additional immunohistochemical stainings were performed for markers of cell injury (NGAL), cell death (cleaved caspase-3, FACL4) and proliferation (Ki-67).

Results

Inter-observer reproducibility was good for pyknosis, flattening, brush border loss, fair for lucency and poor for nuclei loss and luminal debris. In protocol biopsies between 6 weeks and 6 months, the degree of ATI remained virtually unchanged. Biopsies for cause had generally higher injury scores. Deceased donor source, delayed graft function, ganciclovir/valganciclovir treatment and urinary tract infection correlated with ATI. The degree of brush border loss, lucency, pyknosis, and FACL4 expression correlated best with impaired allograft function. Only in patients with tubular Ki-67 expression long-term allograft function improved.

Conclusion

Reliable assessment of ATI is possible by semi-quantitative grading of tubular epithelial cell brush border loss, lucency and pyknosis, and the novel ferroptosis marker FACL4. Examination of Ki-67 expression can help determine the potential for recovery from this damage.