Antithrombin Perfluorocarbon Nanoparticles Improve Renal Allograft Function in a Murine Deceased Criteria Donor Model

Transplantation Direct
Chandu VemuriWilliam C Chapman

Abstract

Over 100 000 patients await renal transplantation and 4000 die per year. Compounding this mismatch between supply and demand is delayed graft function which contributes to short-term and long-term graft failures. Previously, we reported that thrombin-targeted perfluorocarbon nanoparticles (PFC-NP) protect kidneys from ischemic renal injury after transient arterial occlusion. Here we hypothesize that perfusion of renal allografts with PFC-NP similarly can protect graft function after an ischemic interval. After 60 minutes of warm ischemia, male Lewis rats underwent left renal explantation followed by renal perfusion with 5 mL of standard perfusate alone (N = 3) or with 0.3 mL of untargeted PFC-NP (N = 5) or 0.3 mL thrombin-targeted of PFC NP functionalized with phenylalanine-proline-arginine-chloromethylketone (PPACK) (PFC-PPACK), an irreversible thrombin inhibitor (N = 5). Kidneys underwent 6 hours of cold storage, followed by transplantation into recipients and native nephrectomy. Animals were euthanized at 24 hours for tissue collection or at 48 hours for blood and renal tissue collection. A survival experiment was performed using the same protocol with saline control (N = 3), PFC-NP (N = 3) or PFC-PPACK (N = 6). Serum creati...Continue Reading

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Citations

Dec 13, 2018·Current Opinion in Organ Transplantation·Disha BahlYasir A Qazi
Nov 4, 2020·Pflügers Archiv : European journal of physiology·Johannes JägersKatja B Ferenz
Aug 3, 2021·Frontiers in Medicine·Sergi CodinaJosep M Cruzado
Jul 26, 2021·Nanomedicine : Nanotechnology, Biology, and Medicine·Ian VargasSamuel A Wickline

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