Date: Monday, May 1, 2017
Session Time: 2:30pm-4:00pm
Presentation Time: 3:18pm-3:30pm
Ischemia reperfusion injury (IRI) at the time of organ harvesting is unavoidable, may cause delayed renal graft function, and is associated with premature graft loss. Kim-1 is a well-known biomarker for acute tubular injury but its biological function in transplantation is unknown. Kidney Injury Molecule-1 (Kim-1) upregulation on renal tubular epithelial cells (TECs) during acute injury allows them to clear apoptotic and necrotic cells, reducing inflammation in native kidney IRI. Our objective was thus to determine if Kim-1 can protect against the severe cold and warm IRI that occurs during renal transplantation. We performed single syngeneic kidney transplants (cold ischemia time 35 mins) from either C57BL/6 Kim-1+/+ or C57BL/6 Kim-1-/- donor mice into C57BL/6 Kim-1+/+ mice, followed by bilateral native nephrectomy. We evaluated serum creatinine, survival, histology, tubular obstruction, cell death (cleaved caspase-3), inflammation (CD68), and Kim-1 expression after 3-7 days (n>=3 per group for each outcome). Kim-1 protein was upregulated in TECs exposed to cold and warm hypoxia in vitro, and in kidney grafts in vivo. Compared to recipients of Kim-1+/+ kidneys, recipients of Kim-1-/- kidneys had significantly more renal dysfunction (creatinine = 15+/-3 vs. 162+/-40 umol/L, p=0.010) and mortality (0/5 vs. 9/12 deaths, p=0.010). Kim-1-/- grafts also showed more tubular obstruction (score = 0.3/5 vs. 4.0/5, p<0.01); tissue damage (tissue injury score = 0.7/5 vs. 3.7/5, p<0.05); infiltrating CD68-postive macrophages (3.8 vs. 10 per field, p=0.002); and apoptosis (cleaved caspase-3= 0.3 vs. 4%, p<0.05). Our data suggest that Kim-1 upregulation in kidney grafts protects against transplant-related IRI and may serve as a therapeutic target for improving graft outcomes.
CITATION INFORMATION: Lee J, Zhang X, Haig A, Lian D, Anderson P, Navaratnam R, Gunaratnam L. Kidney Injury Molecule-1 Mitigates Tissue Damage from Transplant Renal Ischemia Reperfusion Injury. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Lee J, Zhang X, Haig A, Lian D, Anderson P, Navaratnam R, Gunaratnam L. Kidney Injury Molecule-1 Mitigates Tissue Damage from Transplant Renal Ischemia Reperfusion Injury. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/kidney-injury-molecule-1-mitigates-tissue-damage-from-transplant-renal-ischemia-reperfusion-injury/. Accessed June 16, 2021.
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