Introduction

Renal ischemia-reperfusion injury (IRI) is inevitable during kidney transplantation leading to oxidative stress and inflammation and is a risk factor for delayed graft function, acute rejection and long-term transplant loss. We previously reported that preoperative fasting in young male mice protects against renal IRI. Since patients are generally of older age and suffer from morbidities, we investigated the effects of preoperative fasting on renal IRI in mice with a different age, gender, body mass and genetic background.

Methods

Male and female F1-FVB/C57BL6-hybrid mice with an average age of 73 weeks and a weight of 47.4 respectively 47.1 grams were randomized to either preoperative normal feeding or fasting for 72 hours, followed by renal IRI. Based on previous results, IRI in males was induced by clamping both renal pedicles for 37 minutes. In females, known to be more resistant to IRI, 60 minutes of ischemia was applied. Wellbeing, bodyweight, kidney function and survival of the animals were monitored until day 28 postoperatively. Histopathological analysis of the kidneys was done in a blinded manner.

Results

Preoperative fasting improved survival after renal IRI in both sexes compared with normal fed mice. All normal fed males (n=8) died or were sacrificed due to morbidity indicative of irreversible kidney failure whereas 7 of 8 fasted males survived. Nine of 11 female controls died or were sacrificed whereas 7 of 10 fasted mice survived. Both fasted groups had a better kidney function shown by lower serum urea levels after IRI. Histopathological analysis showed less acute tubular necrosis and more regeneration in kidneys from fasted mice. In the surviving mice, bodyweight gradually decreased in the first two weeks but slowly increased in the weeks thereafter.

Conclusions

Similar to young healthy male mice, preoperative fasting protects against renal IRI in both male and female aged obese mice. These findings suggest a general protective response of dietary restriction against renal IRI regardless of age, sex, body mass and genetic background. Therefore, dietary restriction could be a non-invasive intervention inducing increased oxidative stress resistance in older and obese patients as well.

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