Franny Jongbloed

201 8 BENEFICIAL EFFECTS OF A PREOPERATIVE DIET INTRODUCTION Dietary restriction (DR) increases resistance to reactive oxygen species (ROS) during both acute and chronic stress, and recently we found that DR at the level of genome function reduces transcriptional stress by attenuating DNA damage accumulation 1-4 . Consequently, DR enhances defense and maintenance mechanisms including cellular programs, enabling resistance to a variety of stressors including ischemia-reperfusion injury (IRI). IRI arises from acute oxidative stress that inevitably occurs during organ (e.g. kidney) transplantation and many other surgical procedures. The phase of ischemia after kidney retrieval leads to hypoxia and an increase in metabolic waste products, while reperfusion after restoration of renal blood flow results in the production of ROS and an inflammatory response 5-7 . Living donor kidney transplantation (LDKT) greatly improves function and survival of the kidney allograft compared to kidneys from deceased donors 8 . Nonetheless, and despite the markedly shorter ischemia times following LDKT, IRI remains a risk factor for poor outcome 9,10 . Amelioration of renal IRI could therefore greatly improve both graft and thereby transplant recipient survival 11 . Previously, we showed that short-term DR counteracts perioperative stress and protects against both renal and hepatic IRI in mice, irrespective of gender, age, body weight and genetic background 12,13 . Subsequently, we demonstrated that this protection could also be induced by dietary deprivation of protein alone for three days prior to renal IRI, indicating that the effects of calorie and protein restriction might act synergistically 14 . Translation of the beneficial effects of short-term DR to humans has mostly proven difficult and unsuccessful 15 . Recently, we reported the results of a randomized, controlled clinical trial which demonstrated that prescription of a combined calorie and protein restricted (CCPR) diet is feasible and safe in living kidney donors, as well as in patients undergoing bariatric surgery 16 . Here, we demonstrate that a CCPR diet has beneficial effects on the postoperative outcomes of both living kidney donors and their kidney transplant recipients. RESULTS Baseline characteristics Thirty-five living kidney donors were randomized into either the CCPR (n=15) or the control group (n=20) between May 2, 2014 and November 18, 2015 (Figure S1). The difference in patient numbers between the groups is due to the additional inclusions to replace dropouts. The baseline characteristics of these 35 donors are listed in Table 1A. Donors in the CCPR group were more often female ( P= 0.024) and consequently had a