Franny Jongbloed

180 CHAPTER 7 reduction of pro-inflammatory cytokines, improved kidney function, and increased survival 7,19 . DR also protects against IRI in aged-obese mice of both sexes, suggesting that the DR-induced effects on the stress response could be broadly applied 11 . It is not clear how the benefits of DR should be translated to humans in a clinical setting. Longer-term DR (e.g., for weeks) is considered undesirable, since feelings of hunger and fatigue and the risk of malnutrition could alter the wellbeing of patients prior to surgery. However, a shorter period could be insufficient to confer the same beneficial effects as in animal studies. Most clinical studies of preoperative DR have been performed in bariatric surgery patients and were designed to evaluate the effects of DR on weight loss and liver size reduction 13,14 . One study showed reduction in steatosis and steatohepatitis after liver resection due to preoperative dietary and fat restriction 20 . We previously used a DR regimen of three days of 30% DR followed by 24 hours of fasting in living kidney donors, which proved to be feasible; unfortunately, this did not induce a beneficial response similar to that seen in mice 15,16 . This could be because the DR duration or restriction level was insufficient, or because the diet did not include PR. Based on this experience 15,16 , we extended the number of days of the diet, and restricted protein intake by 80% in addition to the 30% DR. A total adherence rate of 71% was reached, which was comparable between kidney donors and morbidly obese patients. Many factors influence adherence, such as the duration of the intervention as well as the frequency of daily doses. Osterberg et al. showed that the average adherence rate in clinical trials ranges between 43 and 78% 21 . They also reported an average adherence rate between 30 and 80% in patients who took three to four medication doses a day 21 , which is comparable to the three to four shakes per day in the restricted diet group of our study. In light of these results, our compliance rate is acceptable considering the fact that these patients did not receive the diet immediately prior to surgery, and therefore did not expect a beneficial effect. Further studies investigating the potential beneficial effects of this dietary regimen might further increase the compliance rate in these patient populations. Safety and discomfort of a preoperative diet are important factors to consider in terms of compliance and applicability. We found that serum albumin, insulin and ferritin measures did not change as a result of the restricted diet, indicating that malnutrition was not induced. As a measurement of discomfort, the VAS nausea scores were significantly increased in patients following the restricted diet, but since the scores did not exceed 2.5 points out of 10, nausea cannot be considered highly clinically relevant. The patients that withdrew early from the diet reported discomfort, mostly gastrointestinal tract-related, as the reason for withdrawal. This discomfort could be due to the liquid composition of the diet, since the change from normal food to liquid meal replacements has a direct effect on defecation. Offering patients more solid nutrition could reduce this discomfort and