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Kidney Week

Abstract: SA-OR13

Evidence for Kidney Involvement in an Acute Graft vs. Host Disease Model of Allogeneic Stem Cell Transplant (HSCT) in Non-Human Primates

Session Information

Category: Onco-Nephrology

  • 1500 Onco-Nephrology

Authors

  • Hingorani, Sangeeta R., Seattle Children's Hospital, Seattle, Washington, United States
  • Jaimes, Edgar A., Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Muthukumar, Thangamani, Weill Cornell Medicine, New York, New York, United States
  • Seshan, Surya V., Weill Cornell Medicine, New York, New York, United States
Background

Kidney injury is increasingly recognized as a significant cause of morbidity and mortality in recipients of HSCT. The frequency of kidney injury can be as high as 73% and among patients with kidney injury who require dialysis, mortality approaches 100%. Acute graft-versus host disease (aGVHD) has emerged as an important risk factor for kidney injury in HSCT patients but whether the kidney itself is a target of aGVHD has not been established. In this study and utilizing a non-human primate model of HSCT we tested the hypothesis that the kidney undergoes inflammatory changes consistent with aGVHD.

Methods

For this study we used a non-human primate (NHP) model of allogeneic HSCT (allo-HCT) and aGVHD, in which a donor graft is transplanted into MHC haploidentical recipients pre-conditioned with myeloablative total body irradiation. Transplant recipients received no post-transplant immunosuppression, which enabled interrogation of the natural history of aGVHD. Apheresis was performed after G-CSF mobilization and an unmanipulated G-CSF mobilized apheresis product was transplanted into MHC haplo-identical transplant recipients in the allo-HCT cohort (N=3). As controls we used normal animals that did not undergo any intervention (N=4). NHP were euthanized one week after transplant and kidneys saved for histology and IHC (CD3, CD20, CD68, CD 56 and Granzyme B).

Results

As expected control kidneys had normal renal histology. In contrast, kidneys from allo-HCT recipients had evidence of mesangiolysis and tubulitis. By IHC we determined increased expression of CD68+ monocyte lineage cells, Granzyme B+ cytotoxic T lymphocytes and CD-3+ T lymphocytes. There was no difference in the expression of CD56+ NK cells while the number of CD20+ B lymphocytes was lower in allo-HCT as compared to controls.

Conclusion

These studies demonstrate that aGVHD results in renal injury characterized by tubulitis and mesangiolysis and linked to increased infiltration by monocytes and T lymphoctes. These findings suggest that the kidneys are a target of aGVHD and may explain the high frequency of acute kidney injury post allo-HCT.

 CD3CD68CD56CD20Granzyme B
Control184.4 ± 17.712.68 ± 3.750.4 ± 9.40.78 ± 0.136.35 ± 9.4
Allo-HCT463.8 ± 22.235.17 ± 5.1 33.3 ± 4.90.37 ± 0.11 165.4 ± 36.4

† P , 0.005 vs Control, ‡ P < 0.0001 vs Control

Funding

  • NIDDK Support