Franny Jongbloed

200 CHAPTER 8 ABSTRACT Dietary restriction prolongs life- and health span and increases stress resistance in numerous species. A previous clinical study showed that five days of combined calorie and protein restriction (CCPR) before invasive surgery was safe in kidney donors and that adherence to the diet was high. In the present study, the effects of preoperative CCPR in living kidney donors and their transplanted kidneys was investigated. Thirty-five living kidney donors were randomized into either the CCPR (n=15) or control (n=20) group. The CCPR diet reduced calorie intake by 30% and protein intake by 80% during the five days immediately prior to organ donation. Donors in the control group had no restrictions and ate their own regular diet. All patients adhered to the diet. From postoperative day (POD) 2 up until month 1, kidney function of the donors was significantly better in the CCPR group compared with control donors. Recipients of CCPR donors also showed significantly improved kidney function compared with their control group. In addition, the recipients of CCPR kidneys showed a significantly lower incidence of slow graft function and acute rejection. CCPR inhibited cellular immune response pathways and activated stress- resistance signaling. Thus, short-term preoperative CCPR significantly improves recovery of kidney function in donors and the function of the transplanted kidney in recipients. These observations are the first to show that the benefits of CCPR can be induced rapidly in humans and that CCPR may be used clinically to improve outcomes in clinical settings involving ischemia-reperfusion damage.