Franny Jongbloed

27 2 FASTING PROTECTS AGED-OVERWEIGHT MICE Preoperative fasting leads to improved kidney function and recovery after IRI To measure the effect of fasting on kidney function after IRI, serum urea and creatinine levels were measured at days 0, POD1 and if applicable, POD2 and POD7 after surgery. Compared to AL fed mice, serum urea levels in male and female fasted aged mice were lower on postoperative day one, which became significant on day 2 (males P= 0.001; females P= 0.016; Figure 2A). Significance could not be determined on day 7 post-IRI as only 2 AL females remained. Serum creatinine did not show statistically significant differences between groups (Figure 2B). Figure 1. Relative body weight and survival. Relative body weight (A) and survival (B) of male and female mice undergoing 37 and 60 minutes of renal ischemia-reperfusion injury (IRI), respectively, preceded by 3-day fasting or ad libitum feeding. In the first week after surgery, both fasted groups gradually lost weight after which they slowly gained weight in the weeks thereafter. Both fasted groups show a significantly improved survival: P= 0.0171 for males, P= 0.0040 for females. M=male, F=female, Adlib=ad libitum fed. Kidney damage after IRI was further assessed by histopathology. After sorting by cause of death, mice found dead and mice that were moribund and sacrificed showed severe acute tubular necrosis (Figure 3A), a major determinant of renal IRI. Median tubular necrosis scores in these groups, with 0 indicating no and 5 severe necrosis, were 5 and 4, respectively, with no significant differences between the two groups, demonstrating that moribund mice indeed suffered from severe kidney failure independent of the day histology was determined. In contrast, the surviving mice had a median pathology score of 1 ( P< 0.001) (Figure 3A). A B