Preoperative Fasting Protects Aged Obese Mice Against Renal Ischemia-Reperfusion Injury.

Abstract

Introduction. Ischemia-reperfusion injury (IRI) is inevitable during kidney transplantation and leads to oxidative stress and inflammation. We previously reported that preoperative fasting in young-lean male mice protects against IRI. Since patients are generally of older age and overweight, factors that may lead to a different response to fasting, we investigated the effects of preoperative fasting on renal IRI in aged overweight male and female mice. Methods. Male and female F1-FVB/C57BL6-hybrid mice, average age 73 weeks weighing 47.2 grams, were randomized to preoperative ad libitum feeding or 3 days fasting, followed by renal IRI. Body weight, kidney function and survival of the animals were monitored until day 28 postoperatively. Histopathology was examined for all animals and scored for acute tubular necrosis and tubular regeneration. All experiments had the approval of the local Animal Experiments Committee of the National Institute of Public Health and the Environment, the Netherlands. Results. Preoperative fasting significantly improved survival after renal IRI in both sexes compared with normal fed mice. Fasted groups had a better kidney function shown by lower serum urea levels after IRI. Histopathology showed less acute tubular necrosis and more regeneration in kidneys from fasted mice. Fasting resulted in a body weight loss of 14-17% in male and female mice. In the first week after IRI, body weight declined followed by recovery in the weeks thereafter. The normal fed mice showed a larger and faster weight loss after IRI. Conclusions. Similar to young-lean, healthy male mice, preoperative fasting protects against renal IRI in aged overweight mice of both genders. These findings suggest a general protective response of fasting against renal IRI regardless of age, gender, body weight and genetic background. Therefore, fasting could be a non-invasive intervention inducing increased oxidative stress resistance in older and overweight patients as well.