Dietary Interventions During Living Kidney Donations (DILKID Trial)

Acute kidney injury (AKI) is one of the most common disorders in hospitalized patients and the incidence of AKI is rapidly rising, especially among high-risk patients. In a meta-analysis including 49 million patients, AKI occurred in every fifth adult and in every third children suffering from an acute illness, defined as critical care with admission to the intensive care unit (ICU), cardiac surgery, trauma, heart failure or underlying disease within the field of haematology/oncology. AKI is associated with substantial mortality, even in non-ICU patients mortality ranges high between 10-20% and AKI severity is related to increased mortality. In addition, non-recovery of kidney function rates between 13-29% and progression to chronic kidney disease (CKD) requiring dialysis after AKI is common. Despite the considerable burden associated with AKI, effective therapeutic approaches, including prevention strategies, are currently lacking.

Since impaired cellular stress resistance contributes to AKI, preconditioning protocols that augment stress resistance such as caloric restriction (CR) are attractive strategies in the search for organprotection. CR protects from kidney damage in rodent models of AKI, induced by either ischemia-reperfusion injury or by injection of nephrotoxic cisplatin. However, the translation of this potential to the clinical setting has been hampered by both the limited understanding of the underlying mechanisms paired with the risk of malnourishment and significant comorbidity in the target patient population in terms of frailty, multi-morbidity or preoperative settings.

Based on more recent results regarding novel dietary regimens, three well-established targeted diets (a fasting mimicking diet, a ketogenic diet and the dietary restriction of sulfur-containing amino acids and the dietary restriction of branched chained amino acids), which already proved their safety and feasibility in both phase-II and I clinical trials, are promising novel targeted dietary strategies beyond CR.

Intermittent fasting with fasting mimicking diets enables the activation of cellular signal transduction similar to CR with high nourishment. Fasting mimicking diet efficiently protects from acute kidney injury in rodents. Human FMD (Prolon®) is a plant-derived diet to achieve fasting-like effects on serum levels of insulin growth factor-1 (IGF-1), insulin growth factor protein-1 (IGFP-1), glucose and ketone bodies, while providing both macro- und micronutrients. Intermitted fasting with fasting mimicking diets have extensively been studied in rodents. Additionally, phase-II and phase-I studies proofed safety, feasibility and favorable outcome in healthy volunteers and patients with autoimmune disorders or diabetes.

Ketogenic diets are high in fat and very low in carbohydrates and result in ketogenesis with the synthesis of ketone bodies, exceeding β-oxidation of fatty acids and anti-inflammation. Furthermore, ketogenic diets extend the lifespan in rodents with preserved physiological functions. Ketone bodies, such as β-hydroxybutyrate, suppress oxidative stress resulting in nephroprotection. Due to their additional neuroprotective effects, ketogenic diets have been in medical use in pharmacoresistant epilepsy proofing their feasibility and safety in humans. Moreover, ketogenic diets in women with ovarian and endometrial cancer revealed favorable effects on physical activity, perceived energy and food cravings. Considering that CR actually does induce ketogenesis due to feeding cycles, ketogenic diets are a key strategy that needs to be examined as a replacement for caloric restriction.