Abstract
BackgroundOne of the main effectors on the quality of life of living-kidney donors is postoperative fatigue. Caloric restriction (CR) and short-term fasting (STF) are associated with improved fitness and increased resistance to acute stress. CR/STF increases the expression of cytoprotective genes, increases immunomodulation via increased anti-inflammatory cytokine production, and decreases the expression of pro-inflammatory markers. As such, nutritional preconditioning by CR or STF represents a non-invasive and cost-effective method that could mitigate the effects of acute surgery-induced stress and postoperative fatigue. To investigate whether preoperative STF contributes to a reduction in fatigue after living-kidney donation, a randomized clinical trial is indicated.MethodsWe aim to determine whether 2.5 days of fasting reduces postoperative fatigue score in subjects undergoing living-kidney donation. In this randomized study, the intervention group will follow a preoperative fasting regime for 2.5 days with a low-dose laxative, while the control group will receive standard care. The main study endpoint is postoperative fatigue, 4 weeks after living-kidney donation. Secondary endpoints include the effect of preoperative fasting on postoperative hospital admission time, the feasibility of STF, and the postoperative recovery of donor and recipient kidney function. This study will provide us with knowledge of the feasibility of STF and confirm its effect on postoperative recovery.DiscussionOur study will provide clinically relevant information on the merits of caloric restriction for living-kidney donors and recipients. We expect to reduce the postoperative fatigue in living-kidney donors and improve the postoperative recovery of living-kidney recipients. It will provide evidence on the clinical merits and potential caveats of preoperative dietary interventions.Trial registrationNetherlands Trial Register NL9262. EudraCT 2020-005445-16. MEC Erasmus MC MEC-2020-0778. CCMO NL74623.078.21
Highlights
One of the main effectors on the quality of life of living-kidney donors is postoperative fatigue
Caloric restriction (CR) can be performed in different regimens, such as 20–40% reduced daily caloric intake for several weeks or longer, or as a more stringent and acute option: short-term fasting (STF), which could be performed right before a period of stress
The benefits of reducing caloric intake have partly been translated to humans: it has been proven feasible and safe in wellnourished patients before living-kidney donation [23,24,25] and was effective in improving radiological and pathological response during neoadjuvant chemotherapy treatment for breast cancer [26]
Summary
One of the main effectors on the quality of life of living-kidney donors is postoperative fatigue. Caloric restriction (CR) and short-term fasting (STF) are associated with improved fitness and increased resistance to acute stress. A preoperative diet employing caloric restriction (CR) might represent a non-invasive and costeffective method that could mitigate postoperative fatigue and other short- and long-term consequences. It has been demonstrated to induce a lower risk of ageassociated diseases and extended life span in pre-clinical studies [6,7,8,9,10] In evolutionary terms, this response intends to promote survival during times of starvation and other types of stress, such as genotoxic stress caused by oxidative DNA damage; we designated it “survival response” [11,12,13,14]. The benefits of reducing caloric intake have partly been translated to humans: it has been proven feasible and safe in wellnourished patients before living-kidney donation [23,24,25] and was effective in improving radiological and pathological response during neoadjuvant chemotherapy treatment for breast cancer [26]
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