Scoring of Distinct Tubular Injury Features and Assessment of Cellular Proliferation and of Non-Apoptotic Cell Death by the Novel Marker FACL4 Allow to Determine the Long-Term Prognosis of Renal Grafts.

A. Bohlmann,¹ J. Schmitz,¹ A. Melk,¹ R. Schmitt,¹ I. Scheffner,¹ V. Broeker,² H. Haller,¹ J. Metzger,³ J. Braesen,¹ W. Gwinner.¹

¹Hannover Medical School, Hannover, Germany
²University of Gothenburg, Gothenburg, Sweden
³Mosaiques Diagnostics, Hannover, Germany

Meeting: 2017 American Transplant Congress

Abstract number: C169

Keywords: Apoptosis, Graft function, Kidney transplantation, Protocol biopsy

Session Information

Session Name: Poster Session C: Kidney Complications III

Session Type: Poster Session

Date: Monday, May 1, 2017

Session Time: 6:00pm-7:00pm

Presentation Time: 6:00pm-7:00pm

Location: Hall D1

Acute tubular injury (ATI) is common in renal grafts and is related to an inferior long-term function. There is no consensus which of the tubular epithelial injury features should be used in the diagnosis and grading of ATI.

Therefore, we examined various features of tubular epithelial cell injury, including brush border loss, lucency, flattening, karyopyknosis, nuclei loss and tubular luminal debris, each graded semi-quantitatively. Markers for proliferation (Ki67), cell injury (NGAL), apoptosis (cleaved caspase-3), and non-apoptotic cell death (FACL4) were detected by immunostaining. Analyses included 521 protocol biopsies taken at 6 weeks, 3 and 6 months after transplantation and 141 biopsies for cause from 204 patients.

Inter-observer reproducibility was good for karyopyknosis (r=0.92), flattening (r=0.86), loss of brush border (r=0.6), fair for lucency (r=0.54) and poor (r<0.5) for nuclei loss and luminal debris. Within the protocol biopsies between 6 weeks and 6 months, the degree of tubular injury remained virtually unchanged. Biopsies for cause had generally higher injury scores. Clinical factors with tight correlation to the injury were donor characteristics (deceased vs. living), delayed graft function, antiviral treatments with ganciclovir or valganciclovir, and urinary tract infection. Among the injury features, brush border loss, lucency, karyopyknosis, and nuclei loss showed significant inverse correlations with the GFR at the time of biopsy and were moderately predictive of the GFR at 1 year post-transplantation (r=-0.27, p<0.001). Tubular Ki67 and NGAL staining was increased in biopsies with high injury scores. Caspase-3 was not detected in the biopsies. FACL4 correlated inversely with the GFR 1 year after ATI diagnosis. Only patients with Ki67 expression had recovery of the GFR 1 year after ATI diagnosis (p=0.014).

Semi-quantitative scoring of brush border loss, lucency, karyopyknosis, and nuclei loss allows reliable assessment of ATI. Long-term graft function is determined by the magnitude of tubular cell proliferation and non-apoptotic cell death.

CITATION INFORMATION: Bohlmann A, Schmitz J, Melk A, Schmitt R, Scheffner I, Broeker V, Haller H, Metzger J, Braesen J, Gwinner W. Scoring of Distinct Tubular Injury Features and Assessment of Cellular Proliferation and of Non-Apoptotic Cell Death by the Novel Marker FACL4 Allow to Determine the Long-Term Prognosis of Renal Grafts. Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Bohlmann A, Schmitz J, Melk A, Schmitt R, Scheffner I, Broeker V, Haller H, Metzger J, Braesen J, Gwinner W. Scoring of Distinct Tubular Injury Features and Assessment of Cellular Proliferation and of Non-Apoptotic Cell Death by the Novel Marker FACL4 Allow to Determine the Long-Term Prognosis of Renal Grafts. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/scoring-of-distinct-tubular-injury-features-and-assessment-of-cellular-proliferation-and-of-non-apoptotic-cell-death-by-the-novel-marker-facl4-allow-to-determine-the-long-term-prognosis-of-renal-graft/. Accessed May 25, 2025.

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