Juriasingani, SmritiJackson, AshleyZhang, Max YulinRuthirakanthan, AushanthDugbartey, George J.Söğütdelen, Emrullah2023-07-182023-07-182021Juriasingani, S., Jackson, A., Zhang, M. Y., Ruthirakanthan, A., Dugbartey, G. J., Sogutdelen, E., ... & Sener, A. (2021). Evaluating the effects of subnormothermic perfusion with AP39 in a novel blood-free model of ex vivo kidney preservation and reperfusion. International Journal of Molecular Sciences, 22(13), 7180.1422-0067http://dx.doi.org/10.3390/ijms22137180https://hdl.handle.net/20.500.12491/11304This research was supported by Physicians Services Incorporated (PSI) Foundation (Grant #18-17) and the Kidney Foundation of Canada (Grant #180015).The use of blood for normothermic and subnormothermic kidney preservation hinders the translation of these approaches and promising therapeutics. This study evaluates whether adding hydrogen sulfide donor AP39 to Hemopure, a blood substitute, during subnormothermic perfusion improves kidney outcomes. After 30 min of renal pedicle clamping, porcine kidneys were treated to 4 h of static cold storage (SCS-4 degrees C) or subnormothermic perfusion at 21 degrees C with Hemopure (H-21 degrees C), Hemopure + 200 nM AP39 (H200nM-21 degrees C) or Hemopure + 1 mu M AP39 (H1 mu M-21 degrees C). Then, kidneys were reperfused with Hemopure at 37 degrees C for 4 h with metabolic support. Perfusate composition, tissue oxygenation, urinalysis and histopathology were analyzed. During preservation, the H200nM-21 degrees C group exhibited significantly higher urine output than the other groups and significantly higher tissue oxygenation than the H1 mu M-21 degrees C group at 1 h and 2h. During reperfusion, the H200nM-21 degrees C group exhibited significantly higher urine output and lower urine protein than the other groups. Additionally, the H200nM-21 degrees C group exhibited higher perfusate pO(2) levels than the other groups and significantly lower apoptotic injury than the H-21 degrees C and the H1 mu M-21 degrees C groups. Thus, subnormothermic perfusion at 21 degrees C with Hemopure + 200 nM AP39 improves renal outcomes. Additionally, our novel blood-free model of ex vivo kidney preservation and reperfusion could be useful for studying other therapeutics.eninfo:eu-repo/semantics/openAccessKidney PreservationKidney TransplantationHydrogen Sulfide (H2S)Normothermic Machine PerfusionCold IschemiaDonationArticle10.3390/ijms221371802213116342812302-s2.0-85108946995Q1WOS:000670999000001Q1