Caspase Inhibition During Cold Storage Improves Graft Function and Histology in a Murine Kidney Transplant Model

Transplantation
Trevor NydamAlkesh Jani

Abstract

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. 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. 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. Caspase inhibi...Continue Reading

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Citations

Jan 23, 2020·Journal of Clinical Medicine·Gertrude J Nieuwenhuijs-MoekeHenri G D Leuvenink
May 15, 2018·Transplantation·Danielle DetelichKorkut Uygun
Nov 11, 2020·Transplantation Proceedings·Robert J PlenterAlkesh H Jani
Nov 19, 2020·International Journal of Molecular Sciences·André Renaldo FernándezMarcos López-Hoyos

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