Caspase Inhibition During Cold Storage Improves Graft Function and Histology in a Murine Kidney Transplant Model.
In: Transplantation, Jg. 102 (2018-09-01), Heft 9, S. 1487-1495
Online
academicJournal
Zugriff:
Background: Prolonged cold ischemia is a risk factor for delayed graft function of kidney transplants, and is associated with caspase-3-mediated apoptotic tubular cell death. We hypothesized that treatment of tubular cells and donor kidneys during cold storage with a caspase inhibitor before transplant would reduce tubular cell apoptosis and improve kidney function after transplant.
Methods: Mouse tubular cells were incubated with either dimethyl sulfoxide (DMSO) or Q-VD-OPh during cold storage in saline followed by rewarming in normal media. For in vivo studies, donor kidneys from C57BL/6 mice were perfused with cold saline, DMSO (vehicle), or QVD-OPh. Donor kidneys were then recovered, stored at 4°C for 60 minutes, and transplanted into syngeneic C57BL/6 recipients.
Results: Tubular cells treated with a caspase inhibitor had significantly reduced capsase-3 protein expression, caspase-3 activity, and apoptotic cell death compared with saline or DMSO (vehicle) in a dose-dependent manner. Treatment of donor kidneys with a caspase inhibitor significantly reduced serum creatinine and resulted in significantly less tubular cell apoptosis, BBI, tubular injury, cast formation, and tubule lumen dilation compared with DMSO and saline-treated kidneys.
Conclusions: Caspase inhibition resulted in decreased tubular cell apoptosis and improved renal function after transplantation. Caspase inhibition may be a useful strategy to prevent cold ischemic injury of donor renal grafts.
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Caspase Inhibition During Cold Storage Improves Graft Function and Histology in a Murine Kidney Transplant Model.
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Autor/in / Beteiligte Person: | Nydam, TL ; Plenter, R ; Jain, S ; Lucia, S ; Jani, A |
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Zeitschrift: | Transplantation, Jg. 102 (2018-09-01), Heft 9, S. 1487-1495 |
Veröffentlichung: | Hagerstown, MD : Lippincott Williams & Wilkins ; <i>Original Publication</i>: Baltimore, Williams & Wilkins., 2018 |
Medientyp: | academicJournal |
ISSN: | 1534-6080 (electronic) |
DOI: | 10.1097/TP.0000000000002218 |
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