We are all very much accustomed to the idea that good nutrition is essential for postoperative success. However, studies show that in case of organ transplantation it seems to be the other way round. Short term dietary restriction or fasting protects the transplanted kidney from failure. It seems that the consequences of ischemia/reperfusion (I/R) injury can be diminished. As a mechanism of this reaction is unclear, recent studies show that glucose supplementation does not interfere with the fasting-induced renal protection.
Renal transplantation is a final treatment option for patients with end-stage renal disease. Delayed graft function is primarily a consequence of I/R injury, as well as related to it immunologic reactions. It significantly contributes to the loss of kidney grafts (1). No wonder that researchers concentrate on finding out which factors could enhance the outcome of kidney transplantation. In 2009 the scientists from Rotterdam, the Netherlands, observed that that 3 days of water-only fasting and 2-4 weeks of 30% diet restriction improved the survival and kidney function following renal I/R injury in mice (2). In addition fasting for 3–4 days improves organ survival in rodent models of orthotopic liver transplantation (3)and heterotopic heart transplantation (4).
Scientists speculate what might be the underlying cause of the beneficial effects of fasting. In the next study they found that dietary restriction increased the expression of cytoprotective and antioxidant genes (5). One of the consequences of nutrient⁄energy deprivation is reduced insulin⁄IGF-1 signaling, which increases stress resistance. It happens exactly through activation of transcription factors leading to mentioned above increased expression of stress resistance genes (6). As a consequence, more efficient and pronounced response of these genes to I/R injury was detected.
The role of glucocorticosteroids is also discussed. As we know, acute stressors (such as for example fasting) cause the activation of hypothalamic–pituitary–adrenal axis and a secretion of the hormone. The well-known anti-inflammatory action of glucocorticosteroids might explain the effects of fasting on I/R injury, which is based on pathologic immune reaction. This hypothesis was indeed discussed during the study published in 2010 (7). Food deprivation significantly increased corticosterone levels in mice. However, further experiments revealed that these are not glucocorticosteroids which do the job. Glucocorticoid receptor blockade (mifeprostone) did not interfere with the protective effects of fasting, while bilateral adrenalectomy obviously caused 100% mortality among mice who underwent I/R injury. This proves the mediation by corticosterone-independent mechanisms.
In spite of all the probable benefits we could achieve from transferring this method to human model, many concerns are aptly raised. The recent comment (8) on the presented above findings highlights the drawbacks of human preoperative food restriction. During fasting, rapid utilization of liver glycogen before surgery may lead to mobilization of muscle glycogen causing muscle weakness after surgery. Moreover fasting increases intestinal permeability and thus permits bacterial translocation. Food deprivation is accompanied by postoperative impaired wound healing. Irritation, headache and gastric discomfort including nausea and vomiting are also common.
Luckily, preoperative supply of carbohydrates triggers an insulin response and reduces many fasting-related adverse effects (9). This would probably dispel many of the doubts. And still the salutary influence of fasting on kidney survival is retained. The another study (10) revealed that glucose actually plays a restricted role in the protective effects of preoperative fasting against I/R injury. A 30% caloric reduction for 3 days was not as beneficial in preventing renal I/R injury as fasting for 3 days with glucose supplementation.
As we see, there is evidence for beneficial effects of fasting. Since the observation has been made that diet restriction extends the lifespan of flies Drosophila melanogaster, scientist try out various applications of fasting. Here we witness the development of possible enhancement of a life-saving treatment that is underwent by around 16 000 patients each year in the US (11). Not every procedure is finished with success, so certainly it is worth trying to enhance the outcome.
Written by: Natalia Neumann
Source:
1.Perico N, Cattaneo D, Sayegh MH, Remuzzi G. Delayed graft function in kidney transplantation. Lancet 2004; 364:1814.
2.Mitchell JR, Verweij M, Brand K et al. Short-term dietary restriction and fasting precondition against ischemia reperfusion injury in mice. Aging Cell. 2010 Feb;9(1):40-53. Epub 2009 Oct 30.
3.Sumimoto R, Southard JH, Belzer FO.Livers from fasted rats acquire resistance to warm and cold ischemia injury. Transplantation. 1993 Apr;55(4):728-32.
4.Nishihara V, Sumimoto R, Fukuda Y et al.Inhibition of warm ischemic injury to rat liver, pancreas, and heart grafts by controlling the nutritional status of both donor and recipient. Surg Today. 1997;27(7):645-50.
5.Verweij M, van Ginhoven TM, Mitchell JR, et al. Fasting protects against hepatic ischemia/reperfusion injury via upregulation of HO-1 and antioxidant defence. Transpl Int 2009, 22(Suppl. 2): 92.
6.Tatar M.Unearthing Loci that influence life span. Sci Aging Knowledge Environ. 2003 Mar 5;2003(9):PE5.
7.Van Ginhoven TM, Van Den Berg JW, Dik WA et al. Preoperative fasting induces protection against renal ischemia/reperfusion injury by a corticosterone-independent mechanism. Transpl Int. 2010 Nov;23(11):1171-8. doi: 10.1111/j.1432-2277.2010.01116.x. Epub 2010 Aug 19.
8.Nakao A Customizing preoperative fasting protocols to reduce ischemia/reperfusion injury. Transplantation. 2011 Oct 15;92(7):726-7.
9.Helminen H, Viitanen H, Sajanti J. Effect of preoperative intravenous carbohydrate loading on preoperative discomfort in elective surgery patients. Eur J Anaesthesiol 2009; 26: 123.
10.Verweij M, van de Ven M, Mitchell JR et al. Glucose supplementation does not interfere with fasting-induced protection against renal ischemia/reperfusion injury in mice. Transplantation. 2011 Oct 15;92(7):752-8.
11.http://www.ustransplant.org/
Want to know more about kidney? Watch on medtube.net: “Kidney – chronic transplant rejection, self-learning module, immunologic disorders”
