NIV Congres

Introduction Renal ischemia-reperfusion injury (IRI) is inevitable during kidney transplantation and leads to oxidative stress, tissue injury and inflammation. IRI is a risk factor for delayed graft function, acute rejection and long-term transplant loss. We have previously reported that preoperative fasting in young-lean C57BL/6 male mice offers robust protection against renal IRI. Since patients are heterogeneous, generally of older age and suffer from (co)morbidities, we investigated the effects of preoperative fasting on renal IRI in mice with a different age, gender, bodyweight 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 ad libitum feeding or fasting for 72 hours, followed by renal IRI. Based on previous results, renal IRI in males was induced by clamping both renal pedicles for 37 minutes. In females, known to be more resistant to ischemic renal damage, 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 by a pathologist.

Results Preoperative fasting significantly improved survival after renal IRI in both sexes compared with ad libitum fed controls. All ad libitum fed males (n=8) died or were sacrificed as a result of morbidity indicative of irreversible kidney failure, whereas 7 of 8 of the fasted males survived in good health (p=0.0171). Nine of 11 ad libitum fed females died or had to be sacrificed, whereas 7 of 10 fasted mice survived (p=0.0040). Fasted mice of both sexes had a better kidney function as shown by lower serum urea levels after IRI. Histopathological analysis showed significantly less acute tubular necrosis and increased regeneration in kidneys from fasted mice. In the surviving mice, bodyweight gradually decreased in the first two postoperative 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, bodyweight and genetic background. Therefore, dietary restriction could be a non-invasive intervention inducing increased oxidative stress resistance in older and obese patients as well.