Protection of endothelial cell function may explain the benefits of nonoxygenated hypothermic machine perfusion (MP) for marginal kidney preservation. However, this hypothesis remains to be tested with a preclinical model. We postulated that MP protects the nitric oxide (NO) signaling pathway, altered by static cold storage (CS), and improves renal circulation recovery compared to CS. The endothelium releases the vasodilator NO in response to flow via either increased endothelial NO synthase (eNOS) expression (KLF2-dependent) or activation of eNOS by phosphorylation (via Akt, PKA or AMPK). Using a porcine model of kidney transplantation, including 1 h of warm ischemia and preserved 24 h by CS or MP (n ¼ 5), we reported that MP did not alter the cortical levels of KLF2 and eNOS at the end of preservation, but significantly increased eNOS activating phosphorylation compared to CS. eNOS phosphorylation appeared AMPK-dependent and was concomitant to an increased NO-dependent vasodilation of renal arteries measured, ex situ, at the end of preservation. In vivo, laser Doppler showed that cortical microcirculation was improved at reperfusion in MP kidneys. In conclusion, we demonstrate for the first time, in a large-animal model, that MP protects the NO signaling pathway, confirming the value of MP for marginal kidney preservation.Abbreviations: Akt, protein kinase B; AMPKa, 5 0 -adenosine monophosphate-activated protein kinase alpha; ANOVA, analysis of variance; CS, cold storage; CTL, control; DCD, donation after circulatory death; eNOS, endothelial nitric oxide synthase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; iNOS, inducible nitric oxide synthase; KLF2, Kruppel-like factor 2; L19, ribosomal protein L19; L-NAME, NGnitro-L-arginine methyl ester; MP, machine perfusion; MPS, machine perfusion solution; NO, nitric oxide; PKA, protein kinase A; RPLPO, ribosomal phosphoprotein large P0 subunit; RT-qPCR, reverse transcriptase quantitative polymerase chain reaction; SEM, standard error of the mean; UW, University of Wisconsin; WI-60, 1 h warm ischemia

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63 Background: Androgen deprivation therapy (ADT) plays an important role in the management of non-metastatic prostate cancer (NMPC). We prospectively assessed the performance of a symptom rating scale, the aging men’s symptoms score (AMS) in relation to other validated QOL tools. Methods: Following ethics approval, 145 patients with a diagnosis of NMPC receiving ADT as part of radical treatment were enrolled after informed consent. Data was collected using the EORTC QLQ-C30, the AMS and the International Index of Erectile Function score (IIEF-5) questionnaires at baseline, 3 months (post ADT) and after ADT was stopped. Results: Eighty six (58.1%) patients had ADT for <9 months, 7 (4.7%) had 9 -18 months and 55 (37.2%) had 27-36 months. A third (32.3%) of patients had moderate/severe symptoms of testosterone deficiency (TD) at baseline vs 62% and 44.4% at time points 2 & 3 (p<0.0001). Severe erectile dysfunction was common and worsened with ADT (45.3% & 74.1% respectively) and did not recover post ADT (p<0.0001). Few (1.6%) patients retained normal erectile function at the end of the study vs 15.6% at baseline. Self-reported QoL using EORTC QLQ C30 (Q.30) remained high at all time points (80.8%, 76.2%,75.8% respectively for a score of 5-7, 7 =very good, 1=very poor). Conclusions: TD due to ADT resulted in significant symptoms only in a subset of patients and not all symptoms resolved post ADT. However, self-reported QoL remained unaffected indicating that andropause symptoms may not affect QoL in radically treated prostate patients. This prospective data validates AMS scale and it could be used in routine clinical practice to assess TD symptoms in this group. [Table: see text]