Dietary Interventions during Living Kidney Donations (DILKID) - an open-label, randomized controlled pilot trial study protocol

Dietary Interventions during Living Kidney Donations (DILKID) - an open-label, randomized controlled pilot trial study protocol | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Dietary Interventions during Living Kidney Donations (DILKID) - an open-label, randomized controlled pilot trial study protocol Luisa Knieps, Sadrija Cukoski, Martin Richard Späth, Karla Johanna Ruth Hoyer-Allo, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7095136/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Background: Acute kidney injury (AKI) is a frequent threat in the clinic known for its substantial morbidity and mortality. However, effective therapeutic approaches for AKI are lacking. Specific diets efficiently prevent kidney damage from various stimuli in rodents. Nevertheless, the successful transfer to the patient setting is still lagging behind, since the optimal diet for humans paired with the underlying, but conserved molecular mechanisms remain unknown. Methods: The Dietary Interventions during Living Kidney Donations (DILKID)-Trial is a four-arm, investigator-initiated, randomized controlled trial performed in an academic setting during living kidney donation in humans. Three dietary interventions - a fasting-mimicking diet, a reduced intake of sulfur-containing amino acids, and a ketogenic diet are tested against a standard control diet. Apart from feasibility, safety and tolerability analyses of these beneficial diets at hand, human tissue samples and biofluids are collected in the DILKID-Trial. These tissue samples are the essential basis to recapitulate the underlying molecular mechanisms of diet-organ protection observed in rodents to man. Discussion: The DILKID-Trial is a truly translational pilot-study at the cross-roads of molecular biology, translational nephrology and transplant medicine. Given their strong protective effects in rodent models of AKI, the beneficial diets examined in the DILKID-Trial may substantially add to our therapeutic armamentarium in the clinic. The molecular analyses will provide important mechanistic insight and indicate therapeutic targets for future pharmacological approaches to protect against kidney injury. As the beneficial effects of dietary preconditioning are not limited to the kidney, the DILKID-Trial is a blueprint for further research in the context diet-induced organ protection in the kidney and beyond. ClinicalTrials.gov: NCT05709600, date of registration: 2023-02-02. https://clinicaltrials.gov/study/NCT05709600?a=1 Organ Protection Resilience Transplant Acute Kidney Injury Dietary Interventions Figures Figure 1 Figure 2 Background Dietary interventions are known to promote longevity and organ protection. Caloric restriction (CR), the simplest dietary intervention, has enormous effects on general health and increased resilience in various model organisms ( 1 , 2 ). Evolutionary conservation of the underlying molecular mechanisms that mediate diet-induced stress-resistance promises the successful transfer of this great potential to the patient setting. In this context, acute kidney injury (AKI) is an important example ( 3 – 5 ). Of note, AKI is one of the most common complications among hospitalized patients already today. Being an aging-associated disease, its incidence will further rise in the future due to the demographic change ( 6 – 8 ). More importantly, AKI comes with substantial mortality being as high as 15% even in the non-intensive care setting ( 9 , 10 ). Non-recovery of kidney function and progression to chronic kidney disease (CKD) that may require kidney replacement therapies are another frequent threat for our patients ( 11 , 12 ). Despite these considerable burdens, effective therapeutic approaches for AKI, including prevention strategies, are not available to date ( 9 ). As impaired cellular stress resistance drives susceptibility to AKI, diet-induced resilience is an innovative approach in search for kidney protection from various damaging stimuli such as ischemia, drug toxicity and sepsis ( 9 , 13 ). Interestingly, dietary interventions have shown an immense potential in preventing kidney injury in rodents, including our own work ( 14 – 18 ). For example, preconditioning with either a diet depleted in sulfur-containing amino acids (SAA) methionine and cysteine, or caloric restriction (CR), using both a limited caloric intake as well as a fasting mimicking diet (FMD) led to significantly improved survival following renal ischemia-reperfusion injury ( 18 ). None of these animals died within 72 hours after the induction of AKI by renal ischemia-reperfusion injury (IRI), whilst this was the case for 50% of the non-preconditioned animals. Kidney function remained normal in preconditioned mice indicating the strong protective effect of these diets ( 18 ). Conclusively, these beneficial diets may be a substantial addition to our therapeutic armamentarium in the clinic. However, the risks of malnourishment in particular in multimorbid and frail nephrology patients, have to be considered calling for a thorough feasibility, safety and tolerability analyses in advance ( 5 , 18 ). Besides, an age-dependent loss of the diet-induced protective effects has been observed in rodent models of AKI ( 19 , 20 ). The beneficial effects of dietary preconditioning may also be reduced in elderly patients ( 7 ). Thus, the knowledge on the underlying molecular mechanisms responsible for the observed diet-induced kidney protection in man is crucial at this point, and may help to develop pharmaceutical approaches in kidney disease ( 3 , 5 , 21 – 24 ). Triggered by these major challenges, we set up the parallel, four-arm, investigator-initiated, randomized-controlled Dietary Interventions during Living Kidney Donations (DILKID) Trial (NCT05709600). The DILKID-Trial examines a low-SAA diet and FMD in the setting of living kidney donation as a human model of renal IRI ( 13 , 25 ). As mice with a restricted caloric intake are in a ketogenic state paired with the recently shown benefits of ketogenic diet (KD) in both kidney disease and among critically ill patients, KD was added as a third, whilst a control diet is a forth dietary intervention arm ( 18 , 26 – 28 ). Thus, feasibility, tolerability and safety of these dietary interventions are the primary outcome measures to identify the optimal diet for humans. Moreover, per protocol of the DILKID-Trial tissue samples and biofluids are collected that allow to study underlying molecular mechanisms of diet-induced kidney protection in humans. This is an important pre-requisite for the development of pharmaceutical approaches. Methods Objectives and Aims The DILKID-Trial is an open-label, investigator-initiated, randomized controlled, pilot trial (RCT) that yields on the study of feasibility, tolerability and safety of beneficial dietary preconditioning regimens in the setting of living kidney donation paired with the collection and biobanking of human material to recapitulate molecular mechanisms of diet-induced kidney protection in mankind. Thus, the concise aims of the DILKID-Trial are: 1) Feasibility, safety and tolerability analyses of dietary preconditioning in the setting of living kidney donation; 2) Recapitulation of the underlying mechanisms mediating diet-induced organ protection in human tissue. Study setting: The DILKID-Trial is conducted at the Department II of Internal Medicine at the University Hospital Cologne, Germany, in close cooperation with the Transplant Centre and the Department of General, Visceral, Thoracic and Transplant Surgery at the University Hospital Cologne, Germany. Trial design: The DILKID-Trial is a monocentric randomized and controlled study. In a parallel group design, four different study arms - FMD, KD, a low-SAA diet and a control group (CG) - are simultaneously examined among kidney donors. Randomized allocation to the different study arms is ensured using a randomization software (ww w.randomizer.at, Institute for Medical Informatics, Statistics and Documentation, University of Graz, Austria). Blinding of the personnel is not feasible due to individual, patient-specific, production of the diets that is conducted at the University Hospital Cologne, Germany. In total, forty living kidney donors paired with their respective recipients (n=40) are randomized, with each study arm comprising ten kidney donors (Figure 1). To participate in the study, both donors and recipients of the living kidney transplant must give their informed consent. The dietary interventions, however, are solely performed among kidney donors. The DILKID-Trial is approved by the Ethics Committee of the Medical Faculty of the University of Cologne (EK 20-1066) and is registered at clinicaltrials.gov (NCT05709600). To date (04/25), the DILKID-Trial has enrolled more than 50% of its target population. Enrolment of the last participant is planned for the first quarter of 2026. Participants The DILKID-Trial recruits donor-recipient pairs, which have successfully completed the preparation for living kidney donation at the University Hospital Cologne, Germany (29, 30). As the dietary interventions are solely performed among kidney donors, they are eligible to take part in the DILKID-Trial, if they meet the following concise inclusion criteria: Patients > 18 years of age Planned living kidney donation Written informed consent by given capacity to contract Kidney donors meeting the following criteria will be excluded from participating in the study: Vegetarian lifestyle Body-Mass-Index (BMI) < 18.5 kg/m 2 Calorie-reduced diet within the preceding four weeks Underlying wasting syndrome Known allergies or intolerance of the ingredients of the diet used Participation in other interventional trials Sample size and recruitment As a proof-of-principle pilot study, the DILKID-Trial focusses on feasibility, safety and tolerability analyses of the diets at hand as primary endpoint. This is accompanied by the recapitulation of molecular mechanisms in diet-induced kidney protection in human tissue as secondary endpoint. As both study endpoints are exploratory, a sample size calculation was waived. Instead, the sample size per group was based on a recent pilot-trial among living kidney donors examining protein and caloric restriction before living kidney donation (25). Eligible participants are recruited during the clinical routine for the preparations of planned kidney donation at the University Hospital Cologne, Germany. After providing written consent, an appointment for the donor’s initial baseline visit is scheduled. This visit takes place at the latest nine days before the planned transplantation. Allocation strategy and randomization After enrolment and before the first baseline visit, patients are allocated to the study arms using a web-based randomization system (ww w.randomizer.at, Institute for Medical Informatics, Statistics and Documentation, University of Graz, Austria). Stratified randomization is performed as a block randomization in a 1:1:1:1 allocation ratio according to a computer-generated randomization schedule, whilst ensuring an equal gender distribution to the respective study groups. Study procedures The study protocol of the DILKID-Trial is based on the Standard Protocol Items: Recommended for Intervention Trials (SPIRIT) guidelines (31). The SPIRIT figure (Table 1) provides an overview of all time points for enrolment, intervention and assessments. Each participating kidney donor attends two visits during participation in the trial. These study-related visits are conducted in addition to the routine pre-transplant examinations. During the first visit, a comprehensive array of parameters is collected in the kidney donor to establish baseline values. This includes vital signs, anthropometric data, initial metabolic conditions and laboratory measurements. A detailed description of the data collection is provided in tables 1 and 2. At this visit, the kidney donors are also provided with and trained regarding their individually manufactured tailored dietary regimen. The diet is consumed in an outpatient setting. During this period, donors are contacted three times at pre-defined time-points by staff of the study center to ensure tolerability, safety, adherence and practical everyday feasibility of the diets. Following the clinical routine, kidney donors and the respective kidney recipients are admitted to the transplantation ward two days prior to planned surgery. The second study visit is conducted the afternoon before the living kidney donation next day. Measurements highlighted in tables 1 and 2 are again performed enabling both inter- and intragroup analyses. As the long-term kidney graft function is examined in the recipients, the pre-transplant patient characteristics of the kidney recipient, i.e. anthropology, pre-existing diseases and medications in addition to laboratory measurements, are examined the day before surgery (Table 2). Table 1 SPIRIT 2013 figure showing DILKID schedule of enrolment, intervention and assessments STUDY PERIOD Enrolment Allocation Visit 1 Diet Visit 2 KTX Follow-up Long-term follow-up TIMEPOINT -9 d -9 d -9 d -8 d -7 d -6 d -5 d -4 d -3 d -2 d -1 d 0 +1 d +2 - +7 d +3, 6, 12, 24 w ENROLMENT: Eligibility screen X Informed consent X Allocation X INTERVENTIONS: FMD X X X X X KD X X X X X X X SAA X X X X X X X CG X X X X X X X ASSESSMENTS: Demographic data X X X X Anthropology* Vital signs Spirometry X X X X X X X X SF-12 (32) QoR-15 (33) X X X X Telephone Call: Feasibility and Adverse Events X X X Diary X X X X X X X Ketone measurement X X X X X X X X 24h urine collection X X Stool sample X X Laboratory measurements I Laboratory measurements II X X X X X X X X Collection and biobanking: kidney, renal vessel, perirenal fat X Operative data collection X Intervention-associated AE X X X X X X X X X X X Postoperative clinical course X X X Outcome X X X Follow-up completion X Continued Table 1: Abbreviations: AE = adverse events, CG = control group, d = days, FMD = fasting mimicking diet, KD = ketogenic diet, KTX = kidney transplantation, QoR-15 = quality of recovery 15-questionnaire, SAA = dietary restriction of sulfur-containing amino acids, SF-12 = short form-health-survey-12, w = weeks. * Anthropology measures examined: height, weight, body mass index, belly circumference, fat mass, fat-free mass, body water, muscle mass. In hospital, the donor continues to adhere to the assigned diet until pre-operative fasting. Intraoperatively, a pre-implantation kidney biopsy of the donor organ is taken for histopathological graft assessment as part of the standard surgical procedure following the recommendations of the European Society for Organ Transplantation (34). When participating in the DILKID-Trial, half of this pre-implantation biopsy core is used for the multi-layered omics approach as described below, whereas the other half is used for routine kidney pathology. Furthermore, perirenal fat and a part of the renal artery is collected for study specific purposes. Post-operative care and monitoring is based on internal surgical standards in the University Hospital Cologne, Germany. In addition to this, laboratory tests to assess kidney function in both donor and recipient are carried out for seven post-operative days on a daily manner. Long-term follow-up is conducted through transplant outpatient visits scheduled 3, 6, 12 and 24 weeks after living kidney donation (Table 1). Table 2: Data collection used in the DILKID-Trial Information Category Item Measurement methods/instruments Performed on Demographic data Age at transplantation, sex, ethnicity Data extraction from medical records Donor/Recipient Anthropology Height, weight, BMI, belly circumference, fat mass, fat-free mass, body water, muscle mas TANITA body analysis scale MC-780MA (TANITA Europe B.V., Amsterdam, the Netherlands) Donor/Recipient Vital signs Blood pressure, heart rate, oxygen saturation, temperature, respiratory rate Standard clinical measurement devices Donor/Recipient Spirometry Glucose utilization, acid load, resting metabolic rate and oxygen utilization Indirect calorimetry (PhysiCal, Deutsche Gesellschaft für Ernährung und Sport, Feldkirchen-Westerham, Germany) Donor Ketone bodies ß-ketones in capillary blood, ß-ketones in urine Self-tested by GlucoMen aero ß-ketone sensor (A. Menarini diagnostics, Florence, Italy), ketostix test strips, (Bayer AG, Leverkusen, Germany) Donor Feasibility Wellbeing, limitations due the diet, hunger, saturation, health-related quality of life, quality of recovery Phone call questionnaire, diet diary, SF-12 questionnaire(32), QoR-15- questionnaire (33) Donor Adverse events Incidence, frequency and severity of adverse events Phone call questionnaire, Data extraction from medical records, CTCAE-criteria (35) Donor/Recipient Pre-existing diseases Chronic kidney disease, chronic cardiovascular disease, chronic liver disease, chronic pulmonary disease, autoimmune disorder, malignancy, Solid Organ Transplantation Data extraction from medical records Donor/Recipient Pre-existing medication Drug, start / stop relative to the day of transplantation, dosage, administration, frequency, adverse event Data extraction from medical records Donor/Recipient Anesthesia Mode of anesthesia, catheter, inotropic support, pre- and intraoperative fluid administration, intraoperative vital signs, complications during anesthesia Data extraction from medical records Donor/Recipient Surgery Operation time, warm ischemia duration, cold ischemia duration, bleeding event, surgical complication Data extraction from medical records Donor/Recipient Postoperative clinical Course Admission / duration ICU, readmission to ICU, treatment at ICU, duration inotropic support, fluid input, urine output, vital signs, postoperative medication Data extraction from medical records Donor/Recipient Laboratory measurements I Laboratory measurements II Serum creatinine, cystatin c, BUN, eGFR, serum alpha-1 microglobulin, uric acid, serum sodium, serum potassium, serum chloride, serum magnesium, LDH, CK, AST, ALT, bilirubin, g-GT, triglycerides, cholesterol (HDL, LDL), leukocytes, platelets, hemoglobin, c-reactive protein, proteinuria, alpha-1 microglobulin in urine, urine creatinine, urine sodium, urine potassium, urine chloride, urine magnesium Amino acids in blood and urine Analyzed in the DIN ISO 15189:2014-accredited central laboratory of the University Hospital of Cologne using standard clinical assays Donor/Recipient Donor Tissue collection and biobanking 24-hour urine collection, stool samples, kidney biopsy, perirenal fatty tissue, kidney vessels Directly snap frozen in liquid nitrogen in the OR, stored at -80 °C- Donor Outcome Time of hospitalization, incidence of AKI, acute transplant rejection Data extraction from medical records, KDIGO classification (36), Banff classification (37) Donor/Recipient Recipient Abbreviations: AKI = acute kidney injury, AST = aspartate aminotransferase, ALT = alanine aminotransferase, BMI = body mass index, BUN = blood urea nitrogen, CK = creatine kinase, CTCAE = common terminology criteria of adverse events ,eGFR=estimated glomerular filtration rate, g-GT = gamma-glutamyl transferase, HDL = high density lipoprotein, HIV/AIDS = human immunodeficiency virus/acquired immune deficiency syndrome, ICU = intensive care unit, KDIGO = kidney diseases improving global outcomes, LDH = lactate dehydrogenase, LDL = low density lipoprotein, OR = operation Room, QoR-15 = quality of recovery-15 questionnaire, RNA = ribonucleotide acids, SF-12 = short-form-healthy-survey- 12. Dietary regimens Fasting Mimicking Diet (FMD) Caloric intake is restricted by using an FMD for five days prior to the planned living kidney donation, as previously described (Figure 1, Table 1) (38, 39). Briefly, FMD consists of a plant-based fasting program (ProLon ® , L-Nutra, Berlin, Germany). Thus, the diet contains 1100 kcal (4600 kJ) with a proportion of 11% protein, 46% fat and 43% carbohydrates on the first day. From the second day onwards, the caloric intake is further reduced to 715 kcal (3000 kJ) with 9% protein, 44% fat and 47% carbohydrates. FMD is prepared daily by the patient at home according to instructions given by the manufacturer. Ketogenic diet (KD) Participants in this group consume an isocaloric ketogenic diet (KD) for seven days before the planned living kidney donation (Figure 1, Table 1). To standardize food intake, KD is carried out using a formula diet. According to the respective patient-specific energy requirements, KD is individually prepared by the DILKID-staff. First, the basal metabolic rate (BMR) is calculated using the Mifflin St. Joer formula (Table 3) (40). The individual daily energy turnover (ET, [kcal/d]) corresponds to the product of the BMR with the activity factor (AF) (Table 3). Based on this calculation, the proportionate composition of the diet components is individually adjusted to match each participant’s ET. The ketogenic diet consists of three different components. The main component is a very high-fat, low-carbohydrate diet (KetoCal 4:1 neutral, Nutricia Milupa GmbH, Erlangen, Germany). Additional protein substitution is provided by K-AM and Fortimel diet (both Nutricia Milupa GmbH, Erlangen, Germany) as calculated based on the individual patient-specific requirements. All these diets are provided as powders facilitating maximum standardization of a patient-specific formula diet. Aiming for an easy and feasible everyday handling, all components are mixed and packaged as a daily ration. Thus, the respective daily portions will be mixed to a formula diet with water by the recipient at home. The ketogenic diet ensures an isocaloric calorie intake consisting of 80% fats (>125g/day), 15% proteins (<100g/day) and 5% carbohydrates (<20g/day). Table 3: Mifflin St. Joar formula and activity factory definition : Mifflin St. Joar formula BMR, [kcal/d]): BMR♀ [kcal/d]: 9.99 x weight + 6.25 x height – 4.92 x age - 161 BMR♂ [kcal/d]: 9.99 x weight + 6.25 x height – 4.92 x age – 5 Activity factory AF 1.2: none or minimal physical activity (seating, lying) AF 1.375: light minimal physical activity (walking for 2h/d) AF 1.55: moderate physical activity (walking for 3h/d) AF 1.725: heavily physical activity (walking for 4h/d) Abbreviations: Age = in years, BMR = basal metabolic rate, height = centimeter (cm), weight = kilogram (kg). Low intake of sulfur containing amino acids (SAA) The limit intake of the sulfur-containing amino acids methionine and cysteine is ensured by the formula diet XMET XCYS Maxamaid (Nutricia Milupa GmbH, Erlangen, Germany) for seven days. The calculation of the individual diet intake per day is carried out as described in Table 3. To ensure an adequate supply of fat and energy, Fortimel powder, Calogen and DuoCal powder (all Nutricia Milupa GmbH, Erlangen, Germany) are added in an individual, patient-specific manner. Again, the various components are packed together as a daily ration and mixing the diet-powder with water results in a formula diet. Of note, neither the total amount of protein nor the daily calorie intake is restricted in this diet, as only SAA are restricted to 10% of the recommended intake. The participant follows the diet for a total of seven days before the planned living kidney donation. Control group (CG) Participants assigned to the control group receive a balanced, isocaloric, moderate protein, low fat and high carbohydrate diet for seven days before the planned transplantation (41). For reasons of standardization, the diet is based on the Fortimel formula diet (Nutricia Milupa GmbH, Erlangen, Germany). The individually required amount is calculated as above (Table 3). The diet is packed into daily portions by the DILKID-staff and the formula diet is achieved by mixing the diet-powder with water. To ensure sufficient salt intake (5 g/day) during the diets, the participants of KD, SAA and CG will take an additional 200ml of drinking bouillon daily. For each dietary regimen, only calorie-free drinks such as water, black coffee or unsweetened tea may be consumed in addition to the diet. Adherence and possible violations of the diet in the form of additional foods intake is documented by the patient in the diet diary daily (Supplementary File 1). Data Collection and management Data collection will occur at different times during the DILKID-Trial (Table 1): before, during and after the respective dietary interventions. Data is collected from both donors and recipients. Patient-related data will be also extracted from medical record systems. A detailed overview of all data categories, including measurement methods, is provided in Table 2. The data collected will be directly saved in pseudonymized form by qualified personnel in an electronic Case Report Form (eCRF). For programming the eCRF, we used the dedicated software package EFS Leadership 7.0 version 1.2 (Questback GmbH, Cologne, Germany). This software meets all Good Epidemiology Practice (GEP) demands (42). Stored data is only accessible for the DILKID-staff and regular back-ups of entered data are stored on Questback servers in Cologne, Germany. Outcome measures Being an exploratory pilot-study, the DILKID-Trial addresses the following two concise aims: 1) Feasibility, tolerability and safety analyses of dietary preconditioning in the setting of living kidney donation; 2) Recapitulation of the underlying molecular mechanisms of diet-induced organ protection detected in rodents in mankind. Primary outcome measures Intra- and intergroup studies of the following a priori defined criteria have been set to determine the feasibility, tolerability and safety of the respective diets examined in line with the recommendations from pilot study reporting (43, 44). Feasibility measures Recruitment: Percentage of donor-recipient pairs accepting dietary preconditioning prior living kidney donation of those offered the intervention. Dietary adherence as recorded in the diary (Supplementary File 1) paired with the measurement of ketone bodies and metabolites of sulfur metabolism including methionine, cystine, s-sulfocysteine and thiosulfate in the donor’s plasma and urine (18, 28, 43). Completion: Percentage of kidney donors completing dietary preconditioning prior living kidney donation. Tolerability measures Daily self-assessment of general well-being of kidney donor adhering to the diet using an analogue visual rating scale embedded in their diary (Supplementary File 1). Regular telephone calls with the donor assessing general well-being during dietary intervention using a standardized questionnaire (Supplementary File 2). Short Form Health Survey-12 (SF-12) and Quality of Recovery Questionnaire (QoR-15, Supplementary File 3) to assess general quality of life (GQL) pre- and postoperatively (33, 45). Safety measures Identification of safety-related changes in liver and kidney function, protein and fat metabolism as quantified by clinical laboratory parameters (Table 2). Assessment of adverse events, including the postoperatively clinical course after living kidney donation in both donor and recipient (Table 2). Examination of kidney graft function as quantified by creatinine, blood urea nitrogen (BUN), cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney molecule-1 (KIM-1) monitored in blood samples of the kidney transplant recipient paired with alpha-1-microglobulin, tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 (TIMP-2 x IGFBP-7, Nephrocheck TM ), and protein levels in recipient’s urine. Occurrence of AKI as classified according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria using serum creatine values or urine output after transplantation (36). Occurrence of acute transplant rejection according to the Banff classification (37). Progression criteria In line with pilot study reporting the following progression criteria have been set a priori for progressing to a large-scale RCT (43, 44). Thus, high feasibility is defined as completion rate > 80%, moderate feasibility as 51–80%, and low feasibility as 80% to be feasible for a large-scale RCT. In contrast, diets with a completion rate reaching moderate feasibility call for further investigation of the collected data. The evidence is considered insufficient to justify further proceeding, if the completion rate of a diet shows low feasibility. Secondary outcome measures To recapitulate molecular mechanisms of diet-induced kidney protection in mankind, the secondary outcome measures in the DILKID-Trials consist of the intergroup diet-induced differences in the kidney metabolome, transcriptome and proteome as compared to the control diet. In this context, a multi-layered omics approach paired with single nucleus RNA sequencing (snRNAseq) and semiquantitative matrix-assisted laser desorption/ionization mass spectrometry imaging (sqMALDI-MSI) will be applied to collected kidney tissue, as previously described (17, 46-49). Briefly, bulk kidney metabolomics will be examined by liquid chromatography coupled to electrospray ionization tandem mass spectrometry. Bulk transcriptome datasets will be generated using the TruSeq Total RNA platform. Nano-liquid chromatography and mass spectrometry will allow to examine diet-induced changes in the renal proteome. Of note, beneficial dietary interventions alter protein persulfidation (S sulfhydration), an evolutionary conserved post-translational modification of cysteine residues linked to cellular stress-resistance, in model organisms. So, the analysis of diet-induced changes in protein persulfidation established by 4 chloro-7-nitrobenzofurazan (NBF-Cl) labelling will accompany bulk proteomics (18, 50, 51). More importantly, the susceptibility of the different tubular epithelial cells regarding AKI varies strongly calling cell type specific approaches (13). Therefore, the addition of snRNAseq will allow to generate a human single-cell atlas of diet-induced transcriptome changes recapitulating the cellular complexity of the human kidney (13). sqMALDI-MSI measurements will additionally facilitate to characterize the cell type specific diet-induced metabolic response in the human kidney on a molecular level. Analysis plan Due to the specific objectives of the DILKID-Trial the analysis plan must be divided into the bioinformatic analyses as part of the multi-layered omics approach described below on the one hand, and the statistical analyses of the collected medical data on the other hand. Medical data collected in the eCRF is converted into a SPSS-compliant binary data file. This enables direct statistical univariate and multivariate analysis of both inter- and intragroup differences using the IBM SPSS Statistics software, version 30.0.0 (IBM Corporation, Armonk, NY, USA). Appropriate statistical tests such as analysis of variance (ANOVA) or non-parametric tests such as Wilcoxon rank test are performed to compare intergroup differences, as well as intragroup longitudinal analyses. Thus, the individual groups are further stratified according to sex and age. Bioinformatic analyses Briefly for snRNAseq, unique molecular identifiers (UMIs) are mapped to the human reference genome using STAR 2.5.3a and Seurat v3 is used for further downstream analyses, including normalization, scaling, and clustering of nuclei (52). To perform gene ontology and pathway analyses the R package topGO (using the elim algorithm with Fisher exact test) and the R package cluster Profiler (version 3.6.0), using the function enrichKEGG.22 is employed in a cell specific manner. Signaling pathway impact analysis (SPIA) is performed with the SPIA package for R, version 2.30.0,23 following the standard workflow of the manual. Regarding proteomics and persulfidomics, mass-spectrometry raw data is processed with Maxquant using default parameters (53). Maxquant output files will further be processed using Perseus (version 1.5.5.3) and R/Bioconductor (54). sqMALDI-MSI data is acquired at a pixel size of 20 μm (x, y) using a beam scan area of 16 × 16 μm. Isotopically 13 C-labeled yeast extracts as well as isotopically 13 C-labeled s-sulfo-DL-cysteine (DLM-8738, Cambridge Isotope Laboratories, Tewksbury, MA, USA) are used as internal standards to ensure cellular specific metabolic quantifications using R as previously described (48). Discussion Dietary preconditioning with CR, FMD and SAA-restricted diets shows great potential in protecting organ function in rodent models of ischemia or drug-induced AKI (15-18). Lacking knowledge of the underlying mechanisms mediating diet-induced organ protection that are conserved in humans paired with the risk of malnourishment in the frail and multimorbid nephrology patients hindered the transfer of this immense potential from bench-to-bedside (4, 5, 22-24). Consequently, we set up the DILKID-Trial to examine these beneficial dietary preconditioning regimens in the context of living kidney donations at the cross-roads of molecular biology, translational nephrology and transplant medicine. Thus, the DILKID-Trial allows to study the feasibility, tolerability and safety of dietary interventions in a controlled academic setting. This is an important goal in translational medicine to justify proceeding to a large-scale RCT following our pre-defined progression criteria and, in turn, will guide on the development of an optimal diet for humans. Besides to feasibility, safety and tolerability analyses of these beneficial diets at hand, DILKID’s bio sampling approach facilitates the confirmation of findings from animal models in humans (Figure 1). In this context, the additional use of snRNAseq and sqMALDI-MSI is a very powerful approach that overcomes key limitations of sole bulk-omics approaches. As the susceptibility of the different renal cell types regarding AKI varies strongly, snRNAseq and sqMALDI-MSI enable cell type specific analyses in the context of diet-induced kidney protection in human material (13). These molecular analyses will provide precious information on pharmacological approaches in the future to protect against organ injury in the kidney and beyond. In this context, overlapping diet-induced changes in cysteine metabolism observed in our rodent IRI model may contain novel promising druggable targets in search of renal resilience (Figure 2) (4, 5, 18). The design of the translational DILKID-Trial comes with several limitations. First, sample size per study arm is small. Thus, also considering the generally excellent outcome in living kidney donation, the efficacy of the interventions is not the primary study endpoint. Second, employing dietary interventions, obviously, comes with the risk of limited dietary adherence, in particular, as dietary preconditioning is performed in an outpatient setting. To face this, telephone and written self-disclosure are used to confirm dietary adherence. More importantly, dietary adherence is additionally confirmed by the analysis of intraindividual changes in measured levels of the SAA cysteine and methionine in both serum and urine, as well as ketone bodies in the FMD and KD groups, respectively. Furthermore, living kidney donors are highly reliable, since they have a high intrinsic motivation towards the success of the intervention through their donation. Of note, all other diets except for FMD are designed as formula diets for maximum standardization paired with an easy everyday handling by the participants to reduce the risk of incorrect intake. Third, the DILKID-personal is not blinded due to individual preparation of the diets at hand. Despite these shortcomings, a major strength of the DILKID-Trial is its design as one of only few randomized-controlled clinical diet studies in transplant medicine to date (5, 25). As a summary, the DILKID-Trial may serve as blueprint when examining dietary and/or nutritional interventions in a controlled academic setting to close the gap from bench to bedside in the context of diet-induced organ protection (55, 56). Conclusion The DILKID-Trial is a truly translational pilot RCT at the cross-roads of molecular biology, translational nephrology and transplant medicine. Thus, DILKID may promote the successful transfer of dietary interventions towards the clinical setting, in addition to the identification of novel druggable approaches to protect organ function from damaging stimuli (55, 56). As the beneficial effects of dietary preconditioning are not limited to the kidney, DILKID will provide insights and a useful template for other fields beyond nephrology. Abbreviations AE = adverse events AF = activity factor AKI = acute kidney injury ALT = alanine aminotransferase ANOVA = analysis of variance AST = aspartate aminotransferase BMR = body mass index BUN = blood urea nitrogen CG = control group CK = creatine kinase CKD = chronic kidney disease CR = calorie restriction CTCAE = common terminology criteria of adverse events D = days DILKID = Dietary Interventions during Living Kidney Donations eCRF = electronic case report form eGFR = estimated glomerular filtration rate ET = energy turnover FMD = fasting mimicking diet GDPR = general data protection regulation GEP = good epidemiology practice g-GT = gamma-glutamyltransferase GQL = general quality of life HDL = high density lipoprotein HIV/AIDS = human immunodeficiency virus / acquired immune deficiency syndrome ICU = intensive care unit IRI = ischemia-reperfusion injury KD = ketogenic diet KDIGO = kidney diseases improving global outcomes LDH = lactate dehydrogenase LDL = low density lipoprotein NTX = kidney transplantation OR = operation room QoR-15 = quality of recovery 15-questionnaire RCT = randomized controlled trial RNA = ribonucleotide acids SAA = dietary restriction of sulfur-containing amino acids SF-12 = short form health survey-12 snRNAseq = single nucleus RNA sequencing SPIA = signaling pathway impact analysis SPIRIT = standard protocol items: recommended for intervention rials SPSS = statistical package for the social sciences sqMALDI-MSI = semiquantitative matrix-assisted laser desorption/ionization mass spectrometry imaging UMIs = unique molecular identifiers W = weeks Declarations Ethics approval and consent to participate The DILKID-Trial has been approved by the Ethics Committee of the Medical Faculty of the University of Cologne (EK 20-1066) and is registered at clinicaltrials.gov (NCT05709600, date of registration 2023-02-02). DILKID is conducted in accordance with the Declaration of Helsinki and the good clinical practice guidelines of the International Conference on Harmonization. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Funding SC is supported by the Cologne Clinician Scientist Program (CCSP) / Faculty of Medicine / University of Cologne during the conduct of the study. FCK is supported by the Cologne Clinician Scientist Program (CCSP) / Faculty of Medicine / University of Cologne, funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) (Project No. 413543196), reports grant from the Else Kröner-Fresenius-Stiftung, during the conduct of the study. Competing interests The Department II of Internal Medicine received research funding from Fresenius Kabi outside the submitted work. RUM served as advisor to AICURIS, GSK, Vertex, Alnylam, Santa Barbara Nutrients and Vifor outside the submitted work. FCK reports consulting fees from Atriva Therapeutics GmbH, outside the submitted work. All other authors report no competing interests. Authors' contributions LK, SC, DS, MT, TW, MK, CK, FCK contribute data acquisition. MRS, KJRHA, VB, FG, RUM, FCK had the research idea. SC, RUM, FCK concepted the study design. FL, AB, GS, BVDB, TJR contribute analyzing techniques. FCK provided funding. Acknowledgements The authors thank the study center of the Department II of Internal Medicine at the University Hospital Cologne for their ongoing support. References Fontana L, Partridge L. Promoting health and longevity through diet: from model organisms to humans. Cell. 2015;161(1):106-18. Mattison JA, Roth GS, Beasley TM, Tilmont EM, Handy AM, Herbert RL, et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature. 2012;489(7415):318-21. Späth MR, Koehler FC, Hoyer-Allo KJR, Grundmann F, Burst V, Müller RU. Preconditioning strategies to prevent acute kidney injury. F1000Research. 2020;9. Koehler FC, Späth MR, Hoyer-Allo KJR, Müller RU. Mechanisms of Caloric Restriction-Mediated Stress-Resistance in Acute Kidney Injury. Nephron. 2022;146(3):234-8. Koehler FC, Späth MR, Meyer AM, Müller RU. Fueling the success of transplantation through nutrition: recent insights into nutritional interventions, their interplay with gut microbiota and cellular mechanisms. Curr Opin Organ Transplant. 2024. Susantitaphong P, Cruz DN, Cerda J, Abulfaraj M, Alqahtani F, Koulouridis I, et al. World incidence of AKI: a meta-analysis. Clinical journal of the American Society of Nephrology : CJASN. 2013;8(9):1482-93. O'Sullivan ED, Hughes J, Ferenbach DA. Renal Aging: Causes and Consequences. Journal of the American Society of Nephrology : JASN. 2017;28(2):407-20. Vanholder R, Annemans L, Bello AK, Bikbov B, Gallego D, Gansevoort RT, et al. Fighting the unbearable lightness of neglecting kidney health: the decade of the kidney. Clin Kidney J. 2021;14(7):1719-30. Ostermann M, Lumlertgul N, Jeong R, See E, Joannidis M, James M. Acute kidney injury. Lancet (London, England). 2025;405(10474):241-56. Rewa O, Bagshaw SM. Acute kidney injury-epidemiology, outcomes and economics. Nature reviews Nephrology. 2014;10(4):193-207. Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney international. 2012;81(5):442-8. See EJ, Jayasinghe K, Glassford N, Bailey M, Johnson DW, Polkinghorne KR, et al. Long-term risk of adverse outcomes after acute kidney injury: a systematic review and meta-analysis of cohort studies using consensus definitions of exposure. Kidney international. 2019;95(1):160-72. Scholz H, Boivin FJ, Schmidt-Ott KM, Bachmann S, Eckardt KU, Scholl UI, et al. Kidney physiology and susceptibility to acute kidney injury: implications for renoprotection. Nature reviews Nephrology. 2021. Mitchell JR, Verweij M, Brand K, van de Ven M, Goemaere N, van den Engel S, et al. Short-term dietary restriction and fasting precondition against ischemia reperfusion injury in mice. Aging cell. 2010;9(1):40-53. Spath MR, Bartram MP, Palacio-Escat N, Hoyer KJR, Debes C, Demir F, et al. The proteome microenvironment determines the protective effect of preconditioning in cisplatin-induced acute kidney injury. Kidney international. 2019;95(2):333-49. Hoyer-Allo KJR, Späth MR, Brodesser S, Zhu Y, Binz-Lotter J, Höhne M, et al. Caloric restriction reduces the pro-inflammatory eicosanoid 20-hydroxyeicosatetraenoic acid to protect from acute kidney injury. Kidney international. 2022;102(3):560-76. Späth MR, Hoyer-Allo KJR, Seufert L, Höhne M, Lucas C, Bock T, et al. Organ Protection by Caloric Restriction Depends on Activation of the De Novo NAD+ Synthesis Pathway. Journal of the American Society of Nephrology : JASN. 2023;34(5):772-92. Koehler FC, Fu CY, Späth MR, Hoyer-Allo KJR, Bohl K, Göbel H, et al. A systematic analysis of diet-induced nephroprotection reveals overlapping changes in cysteine catabolism. Transl Res. 2022. Andrianova NV, Jankauskas SS, Zorova LD, Pevzner IB, Popkov VA, Silachev DN, et al. Mechanisms of Age-Dependent Loss of Dietary Restriction Protective Effects in Acute Kidney Injury. Cells. 2018;7(10). Andrianova NV, Zorova LD, Pevzner IB, Popkov VA, Chernikov VP, Silachev DN, et al. Resemblance and differences in dietary restriction nephroprotective mechanisms in young and old rats. Aging. 2020;12(18):18693-715. Koehler FC, Späth MR, Hoyer-Allo KJR, Müller RU. Mechanisms of Caloric Restriction-Mediated Stress-Resistance in Acute Kidney Injury. Nephron. 2021:1-5. Grundmann F, Muller RU, Reppenhorst A, Hulswitt L, Spath MR, Kubacki T, et al. Preoperative Short-Term Calorie Restriction for Prevention of Acute Kidney Injury After Cardiac Surgery: A Randomized, Controlled, Open-Label, Pilot Trial. J Am Heart Assoc. 2018;7(6). Grundmann F, Müller RU, Hoyer-Allo KJR, Späth MR, Passmann E, Becker I, et al. Dietary restriction for prevention of contrast-induced acute kidney injury in patients undergoing percutaneous coronary angiography: a randomized controlled trial. Scientific reports. 2020;10(1):5202. Osterholt T, Gloistein C, Todorova P, Becker I, Arenskrieger K, Melka R, et al. Preoperative Short-Term Restriction of Sulfur-Containing Amino Acid Intake for Prevention of Acute Kidney Injury After Cardiac Surgery: A Randomized, Controlled, Double-Blind, Translational Trial. J Am Heart Assoc. 2022;11(17):e025229. Jongbloed F, de Bruin RWF, Steeg HV, Beekhof P, Wackers P, Hesselink DA, et al. Protein and calorie restriction may improve outcomes in living kidney donors and kidney transplant recipients. Aging. 2020;12(13):12441-67. Rahmel T, Effinger D, Bracht T, Griep L, Koos B, Sitek B, et al. An open-label, randomized controlled trial to assess a ketogenic diet in critically ill patients with sepsis. Science translational medicine. 2024;16(755):eadn9285. Knol MGE, Wulfmeyer VC, Müller RU, Rinschen MM. Amino acid metabolism in kidney health and disease. Nature reviews Nephrology. 2024. Cukoski S, Lindemann CH, Arjune S, Todorova P, Brecht T, Kühn A, et al. Feasibility and impact of ketogenic dietary interventions in polycystic kidney disease: KETO-ADPKD-a randomized controlled trial. Cell Rep Med. 2023;4(11):101283. Chadban SJ, Ahn C, Axelrod DA, Foster BJ, Kasiske BL, Kher V, et al. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation. 2020;104(4S1 Suppl 1):S11-s103. Lentine KL, Kasiske BL, Levey AS, Adams PL, Alberú J, Bakr MA, et al. KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors. Transplantation. 2017;101(8S Suppl 1):S1-s109. Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158(3):200-7. Wirtz MA, Morfeld M, Glaesmer H, Brähler E. Normierung des SF-12 Version 2.0 zur Messung der gesundheitsbezogenen Lebensqualität in einer deutschen bevölkerungsrepräsentativen Stichprobe. Diagnostica. 2018;64(4):215-26. Stark PA, Myles PS, Burke JA. Development and psychometric evaluation of a postoperative quality of recovery score: the QoR-15. Anesthesiology. 2013;118(6):1332-40. Zaza G, Cucchiari D, Becker JU, de Vries APJ, Eccher A, Florquin S, et al. European Society for Organ Transplantation (ESOT)-TLJ 3.0 Consensus on Histopathological Analysis of Pre-Implantation Donor Kidney Biopsy: Redefining the Role in the Process of Graft Assessment. Transpl Int. 2023;36:11410. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. In: Service USDoHaH, editor. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf2017. Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clinical practice. 2012;120(4):c179-84. Solez K, Axelsen RA, Benediktsson H, Burdick JF, Cohen AH, Colvin RB, et al. International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology. Kidney Int. 1993;44(2):411-22. Wei M, Brandhorst S, Shelehchi M, Mirzaei H, Cheng CW, Budniak J, et al. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med. 2017;9(377). Caffa I, Spagnolo V, Vernieri C, Valdemarin F, Becherini P, Wei M, et al. Fasting-mimicking diet and hormone therapy induce breast cancer regression. Nature. 2020;583(7817):620-4. Mifflin MD, St Jeor ST, Hill LA, Scott BJ, Daugherty SA, Koh YO. A new predictive equation for resting energy expenditure in healthy individuals. The American Journal of Clinical Nutrition. 1990;51(2):241-7. Bantle JP, Wylie-Rosett J, Albright AL, Apovian CM, Clark NG, Franz MJ, et al. Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association. Diabetes care. 2008;31 Suppl 1:S61-78. Hoffmann W, Latza U, Baumeister SE, Brunger M, Buttmann-Schweiger N, Hardt J, et al. Guidelines and recommendations for ensuring Good Epidemiological Practice (GEP): a guideline developed by the German Society for Epidemiology. European journal of epidemiology. 2019;34(3):301-17. El-Kotob R, Giangregorio LM. Pilot and feasibility studies in exercise, physical activity, or rehabilitation research. Pilot Feasibility Stud. 2018;4:137. Thabane L, Ma J, Chu R, Cheng J, Ismaila A, Rios LP, et al. A tutorial on pilot studies: the what, why and how. BMC Med Res Methodol. 2010;10:1. Ware J, Jr., Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Medical care. 1996;34(3):220-33. Wu H, Dixon EE, Xuanyuan Q, Guo J, Yoshimura Y, Debashish C, et al. High resolution spatial profiling of kidney injury and repair using RNA hybridization-based in situ sequencing. Nat Commun. 2024;15(1):1396. McEvoy CM, Murphy JM, Zhang L, Clotet-Freixas S, Mathews JA, An J, et al. Single-cell profiling of healthy human kidney reveals features of sex-based transcriptional programs and tissue-specific immunity. Nat Commun. 2022;13(1):7634. Wang G, van den Berg BM, Kostidis S, Pinkham K, Jacobs ME, Liesz A, et al. Spatial quantitative metabolomics enables identification of remote and sustained ipsilateral cortical metabolic reprogramming after stroke. bioRxiv. 2024:2024.10.26.620403. Wang G, Heijs B, Kostidis S, Mahfouz A, Rietjens RGJ, Bijkerk R, et al. Analyzing cell-type-specific dynamics of metabolism in kidney repair. Nature metabolism. 2022;4(9):1109-18. Zivanovic J, Kouroussis E, Kohl JB, Adhikari B, Bursac B, Schott-Roux S, et al. Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration. Cell metabolism. 2019;30(6):1152-70.e13. Hine C, Harputlugil E, Zhang Y, Ruckenstuhl C, Lee BC, Brace L, et al. Endogenous hydrogen sulfide production is essential for dietary restriction benefits. Cell. 2015;160(1-2):132-44. Satija R, Farrell JA, Gennert D, Schier AF, Regev A. Spatial reconstruction of single-cell gene expression data. Nat Biotechnol. 2015;33(5):495-502. Cox J, Mann M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nature biotechnology. 2008;26(12):1367-72. Tyanova S, Temu T, Sinitcyn P, Carlson A, Hein MY, Geiger T, et al. The Perseus computational platform for comprehensive analysis of (prote)omics data. Nature methods. 2016;13(9):731-40. Woolf SH. The meaning of translational research and why it matters. Jama. 2008;299(2):211-3. Utz PJ, Jain MK, Cheung VG, Kobilka BK, Lefkowitz R, Yamada T, et al. Translating science to medicine: The case for physician-scientists. Science translational medicine. 2022;14(632):eabg7852. Supplementary Files Supplementaryfile1diarycontrolgroup.docx Supplementfile2telephonelog.docx Supplementfile3QoR15english.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 22 Dec, 2025 Reviewers invited by journal 20 Aug, 2025 Editor assigned by journal 29 Jul, 2025 First submitted to journal 23 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7095136","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":502980913,"identity":"e8925c0d-d7a7-4f3f-88de-d50b8969b878","order_by":0,"name":"Luisa Knieps","email":"","orcid":"","institution":"University Hospital Cologne: Universitatsklinikum Koln","correspondingAuthor":false,"prefix":"","firstName":"Luisa","middleName":"","lastName":"Knieps","suffix":""},{"id":502980914,"identity":"a635c648-c91a-4b22-99cf-7f76aa532366","order_by":1,"name":"Sadrija Cukoski","email":"","orcid":"","institution":"University Hospital Cologne: 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Koln","correspondingAuthor":true,"prefix":"","firstName":"Felix","middleName":"Carlo","lastName":"Koehler","suffix":""}],"badges":[],"createdAt":"2025-07-10 17:05:45","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7095136/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7095136/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90306720,"identity":"777118f1-9932-4341-b9bd-87687cf3c457","added_by":"auto","created_at":"2025-09-01 09:28:31","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":165756,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eWorkflow of the Dietary Interventions during Living Kidney Donations (DILKID)-Trial.\u003c/strong\u003e The\u003cstrong\u003e \u003c/strong\u003eDILKID-Trial is a parallel group, four-arm, randomized controlled, clinical trial conducted among living kidney donors and their respective recipients. Forty kidney donors together with their respective kidney recipients are eligible to the DILKID-Trial. After a baseline visit each kidney donor is assigned to: Caloric restriction using a fasting mimicking diet for five days prior kidney donation or a ketogenic or a sulfur amino acids (SAA) restricted diet, each for seven days prior kidney donation. The control diet is a balanced, isocaloric, moderate protein, low fat and high carbohydrate diet.Biofluid samples are collected per protocol in the baseline first visit prior dietary interventions as well as in the so-called second visit after dietary interventions before surgery. During the transplantation procedure, tissue samples of the kidney, renal vessels and perirenal fat are obtained and collected as part of the surgical routine. Simultaneously, feasibility, tolerability and safety are assessed in the donor in addition to kidney function in the recipient. Abbreviations: DILKID = Dietary Interventions during Living Kidney Donations, SAA = dietary restriction of sulfur-containing amino acids.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7095136/v1/7b5a12c0629b9bd837c50a30.png"},{"id":90306721,"identity":"7b603cc2-785b-43b6-b32f-498e1a328d54","added_by":"auto","created_at":"2025-09-01 09:28:31","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":731828,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRecapitulation of underlying mechanisms in human material may facilitate the identification of druggable targets. \u003c/strong\u003eThe DILKID-Trial is a truly translational randomized-controlled pilot-study that may close the gap between bench to bedside in search of diet-induced protection in the kidney (55, 56). In previous work, we systematically analyzed different dietary interventions with regard to their efficacy in a rodent model of renal ischemia-reperfusion injury (IRI) induced acute kidney injury (AKI) (18). Protective dietary preconditioning regimens are now studied in the context of a living kidney donation in of the DILKID-Trial. Apart from feasibility, tolerability and safety analyses, a human biobank is being established that allows to recapitulate mechanisms of diet-induced kidney protection in human material. This is an important pre-requisite in search of novel pharmacological approaches in the future to protect from organ injury in the kidney and beyond. Overlapping diet-induced changes in cysteine metabolism observed in our rodent IRI model are promising starting-point in search of novel pharmaceutical approaches for AKI. Abbreviations: AKI = Acute Kidney Injury, DILKID = Dietary Interventions during Living Kidney Donations, IRI = Ischemia-Reperfusion Injury. Figure created with bioRender.com.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7095136/v1/984e12aaa9883c32aba11140.png"},{"id":90310612,"identity":"fa254ee3-0966-4fed-aec2-963eb9b5bbc2","added_by":"auto","created_at":"2025-09-01 09:44:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2179671,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7095136/v1/41fbad21-6761-452f-bcf4-a128991fb6ef.pdf"},{"id":90308091,"identity":"b08eed23-cdbf-425d-8648-f84dfbe88ab5","added_by":"auto","created_at":"2025-09-01 09:36:31","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":240744,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryfile1diarycontrolgroup.docx","url":"https://assets-eu.researchsquare.com/files/rs-7095136/v1/b53e40c0d2586c78c5a7e629.docx"},{"id":90308089,"identity":"11fd825d-a4d2-44ef-ab74-d24720816c40","added_by":"auto","created_at":"2025-09-01 09:36:31","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":119491,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementfile2telephonelog.docx","url":"https://assets-eu.researchsquare.com/files/rs-7095136/v1/baafae30cd0ec9252bd1048e.docx"},{"id":90306725,"identity":"962f65a7-6b62-47cd-bd1a-882d1801dc61","added_by":"auto","created_at":"2025-09-01 09:28:31","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":392060,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementfile3QoR15english.docx","url":"https://assets-eu.researchsquare.com/files/rs-7095136/v1/8d84874b26d8d587f1b59705.docx"}],"financialInterests":"","formattedTitle":"Dietary Interventions during Living Kidney Donations (DILKID) - an open-label, randomized controlled pilot trial study protocol","fulltext":[{"header":"Background","content":"\u003cp\u003eDietary interventions are known to promote longevity and organ protection. Caloric restriction (CR), the simplest dietary intervention, has enormous effects on general health and increased resilience in various model organisms (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Evolutionary conservation of the underlying molecular mechanisms that mediate diet-induced stress-resistance promises the successful transfer of this great potential to the patient setting.\u003c/p\u003e\u003cp\u003eIn this context, acute kidney injury (AKI) is an important example (\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Of note, AKI is one of the most common complications among hospitalized patients already today. Being an aging-associated disease, its incidence will further rise in the future due to the demographic change (\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). More importantly, AKI comes with substantial mortality being as high as 15% even in the non-intensive care setting (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Non-recovery of kidney function and progression to chronic kidney disease (CKD) that may require kidney replacement therapies are another frequent threat for our patients (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Despite these considerable burdens, effective therapeutic approaches for AKI, including prevention strategies, are not available to date (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAs impaired cellular stress resistance drives susceptibility to AKI, diet-induced resilience is an innovative approach in search for kidney protection from various damaging stimuli such as ischemia, drug toxicity and sepsis (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Interestingly, dietary interventions have shown an immense potential in preventing kidney injury in rodents, including our own work (\u003cspan additionalcitationids=\"CR15 CR16 CR17\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). For example, preconditioning with either a diet depleted in sulfur-containing amino acids (SAA) methionine and cysteine, or caloric restriction (CR), using both a limited caloric intake as well as a fasting mimicking diet (FMD) led to significantly improved survival following renal ischemia-reperfusion injury (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). None of these animals died within 72 hours after the induction of AKI by renal ischemia-reperfusion injury (IRI), whilst this was the case for 50% of the non-preconditioned animals. Kidney function remained normal in preconditioned mice indicating the strong protective effect of these diets (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eConclusively, these beneficial diets may be a substantial addition to our therapeutic armamentarium in the clinic. However, the risks of malnourishment in particular in multimorbid and frail nephrology patients, have to be considered calling for a thorough feasibility, safety and tolerability analyses in advance (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eBesides, an age-dependent loss of the diet-induced protective effects has been observed in rodent models of AKI (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). The beneficial effects of dietary preconditioning may also be reduced in elderly patients (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Thus, the knowledge on the underlying molecular mechanisms responsible for the observed diet-induced kidney protection in man is crucial at this point, and may help to develop pharmaceutical approaches in kidney disease (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR22 CR23\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eTriggered by these major challenges, we set up the parallel, four-arm, investigator-initiated, randomized-controlled Dietary Interventions during Living Kidney Donations (DILKID) Trial (NCT05709600). The DILKID-Trial examines a low-SAA diet and FMD in the setting of living kidney donation as a human model of renal IRI (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). As mice with a restricted caloric intake are in a ketogenic state paired with the recently shown benefits of ketogenic diet (KD) in both kidney disease and among critically ill patients, KD was added as a third, whilst a control diet is a forth dietary intervention arm (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Thus, feasibility, tolerability and safety of these dietary interventions are the primary outcome measures to identify the optimal diet for humans. Moreover, per protocol of the DILKID-Trial tissue samples and biofluids are collected that allow to study underlying molecular mechanisms of diet-induced kidney protection in humans. This is an important pre-requisite for the development of pharmaceutical approaches.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eObjectives and Aims\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe DILKID-Trial is an open-label, investigator-initiated, randomized controlled, pilot trial (RCT) that yields on the study of feasibility, tolerability and safety of beneficial dietary preconditioning regimens in the setting of living kidney donation paired with the collection and biobanking of human material to recapitulate molecular mechanisms of diet-induced kidney protection in mankind. Thus, the concise aims of the DILKID-Trial are: 1) Feasibility, safety and tolerability analyses of dietary preconditioning in the setting of living kidney donation; 2) Recapitulation of the underlying mechanisms mediating diet-induced organ protection in human tissue.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy setting:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe DILKID-Trial is conducted at the Department II of Internal Medicine at the University Hospital Cologne, Germany, in close cooperation with the Transplant Centre and the Department of General, Visceral, Thoracic and Transplant Surgery at the University Hospital Cologne, Germany.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial design:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe DILKID-Trial is a monocentric randomized and controlled study. In a parallel group design, four different study arms - FMD, KD, a low-SAA diet and a control group (CG) - are simultaneously examined among kidney donors. Randomized allocation to the different study arms is ensured using a randomization software (ww\u003cem\u003ew.randomizer.at,\u003c/em\u003e Institute for Medical Informatics, Statistics and Documentation, University of Graz, Austria).\u003c/p\u003e\n\u003cp\u003eBlinding of the personnel is not feasible due to individual, patient-specific, production of the diets that is conducted at the University Hospital Cologne, Germany. In total, forty living kidney donors paired with their respective recipients (n=40) are randomized, with each study arm comprising ten kidney donors (Figure 1). To participate in the study, both donors and recipients of the living kidney transplant must give their informed consent. The dietary interventions, however, are solely performed among kidney donors.\u003c/p\u003e\n\u003cp\u003eThe DILKID-Trial is approved by the Ethics Committee of the Medical Faculty of the University of Cologne (EK 20-1066) and is registered at \u003cem\u003eclinicaltrials.gov\u003c/em\u003e (NCT05709600). To date (04/25), the DILKID-Trial has enrolled more than 50% of its target population. Enrolment of the last participant is planned for the first quarter of 2026.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParticipants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe DILKID-Trial recruits donor-recipient pairs, which have successfully completed the preparation for living kidney donation at the University Hospital Cologne, Germany (29, 30). As the dietary interventions are solely performed among kidney donors, they are eligible to take part in the DILKID-Trial, if they meet the following concise inclusion criteria:\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003ePatients \u0026gt; 18 years of age\u003c/li\u003e\n \u003cli\u003ePlanned living kidney donation\u003c/li\u003e\n \u003cli\u003eWritten informed consent by given capacity to contract\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eKidney donors meeting the following criteria will be excluded from participating in the study:\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eVegetarian lifestyle\u003c/li\u003e\n \u003cli\u003eBody-Mass-Index (BMI) \u0026lt; 18.5 kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/li\u003e\n \u003cli\u003eCalorie-reduced diet within the preceding four weeks\u003c/li\u003e\n \u003cli\u003eUnderlying wasting syndrome\u003c/li\u003e\n \u003cli\u003eKnown allergies or intolerance of the ingredients of the diet used\u003c/li\u003e\n \u003cli\u003eParticipation in other interventional trials\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eSample size and recruitment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs a proof-of-principle pilot study, the DILKID-Trial focusses on feasibility, safety and tolerability analyses of the diets at hand as primary endpoint. This is accompanied by the recapitulation of molecular mechanisms in diet-induced kidney protection in human tissue as secondary endpoint. As both study endpoints are exploratory, a sample size calculation was waived. Instead, the sample size per group was based on a recent pilot-trial among living kidney donors examining protein and caloric restriction before living kidney donation (25).\u003c/p\u003e\n\u003cp\u003eEligible participants are recruited during the clinical routine for the preparations of planned kidney donation at the University Hospital Cologne, Germany. After providing written consent, an appointment for the donor\u0026rsquo;s initial baseline visit is scheduled. This visit takes place at the latest nine days before the planned transplantation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAllocation strategy and randomization\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter enrolment and before the first baseline visit, patients are allocated to the study arms using a web-based randomization system (ww\u003cem\u003ew.randomizer.at,\u003c/em\u003e Institute for Medical Informatics, Statistics and Documentation, University of Graz, Austria). Stratified randomization is performed as a block randomization in a 1:1:1:1 allocation ratio according to a computer-generated randomization schedule, whilst ensuring an equal gender distribution to the respective study groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy procedures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol of the DILKID-Trial is based on the Standard Protocol Items: Recommended for Intervention Trials (SPIRIT) guidelines (31). The SPIRIT figure (Table 1) provides an overview of all time points for enrolment, intervention and assessments.\u003c/p\u003e\n\u003cp\u003eEach participating kidney donor attends two visits during participation in the trial. These study-related visits are conducted in addition to the routine pre-transplant examinations. During the first visit, a comprehensive array of parameters is collected in the kidney donor to establish baseline values. This includes vital signs, anthropometric data, initial metabolic conditions and laboratory measurements. A detailed description of the data collection is provided in tables 1 and 2. At this visit, the kidney donors are also provided with and trained regarding their individually manufactured tailored dietary regimen. The diet is consumed in an outpatient setting. During this period, donors are contacted three times at pre-defined time-points by staff of the study center to ensure tolerability, safety, adherence and practical everyday feasibility of the diets. Following the clinical routine, kidney donors and the respective kidney recipients are admitted to the transplantation ward two days prior to planned surgery. The second study visit is conducted the afternoon before the living kidney donation next day. Measurements highlighted in tables 1 and 2 are again performed enabling both inter- and intragroup analyses.\u003c/p\u003e\n\u003cp\u003eAs the long-term kidney graft function is examined in the recipients, the pre-transplant patient characteristics of the kidney recipient, i.e. anthropology, pre-existing diseases and medications in addition to laboratory measurements, are examined the day before surgery (Table 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1 SPIRIT 2013 figure showing DILKID schedule of enrolment, intervention and assessments\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"906\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"15\"\u003e\n \u003cp\u003e\u003cstrong\u003eSTUDY PERIOD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eEnrolment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eAllocation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eVisit 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiet\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eVisit 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eKTX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eFollow-up\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eLong-term follow-up\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eTIMEPOINT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e-9 d\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e-9 d\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e-9 d\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e-8 d\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e-7 d\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e-6 d\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e-5 d\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e-4 d\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e-3 d\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e-2 d\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e-1 d\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e+1 d\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e+2 - +7 d\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e+3, 6, 12, 24\u0026nbsp;w\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eENROLMENT:\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eEligibility screen\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eInformed consent\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eAllocation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eINTERVENTIONS:\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eFMD\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eKD\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eSAA\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eCG\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eASSESSMENTS:\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eDemographic data\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eAnthropology*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eVital signs\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSpirometry\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n 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\u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eCollection and biobanking: kidney, renal vessel, perirenal fat\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eOperative data collection\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eIntervention-associated AE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ePostoperative clinical course\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eOutcome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eFollow-up completion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eContinued Table 1:\u003c/strong\u003e Abbreviations: AE = adverse events, CG = control group, d = days, FMD = fasting mimicking diet, KD = ketogenic diet, KTX = kidney transplantation, QoR-15 = quality of recovery 15-questionnaire, SAA = dietary restriction of sulfur-containing amino acids, SF-12 = short form-health-survey-12, w = weeks. \u003cstrong\u003e*\u003c/strong\u003eAnthropology measures examined: height, weight, body mass index, belly circumference, fat mass, fat-free mass, body water, muscle mass.\u003c/p\u003e\n\u003cp\u003eIn hospital, the donor continues to adhere to the assigned diet until pre-operative fasting. Intraoperatively, a pre-implantation kidney biopsy of the donor organ is taken for histopathological graft assessment as part of the standard surgical procedure following the recommendations of the European Society for Organ Transplantation (34). When participating in the DILKID-Trial, half of this pre-implantation biopsy core is used for the multi-layered omics approach as described below, whereas the other half is used for routine kidney pathology. Furthermore, perirenal fat and a part of the renal artery is collected for study specific purposes. Post-operative care and monitoring is based on internal surgical standards in the University Hospital Cologne, Germany. In addition to this, laboratory tests to assess kidney function in both donor and recipient are carried out for seven post-operative days on a daily manner. Long-term follow-up is conducted through transplant outpatient visits scheduled 3, 6, 12 and 24 weeks after living kidney donation (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: Data collection used in the DILKID-Trial\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"614\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eInformation Category\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eItem\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMeasurement methods/instruments\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePerformed on\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDemographic data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAge at transplantation, sex, ethnicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eData extraction from medical records\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDonor/Recipient\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAnthropology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHeight, weight, BMI, belly circumference,\u003c/p\u003e\n \u003cp\u003efat mass, fat-free mass, body water, muscle mas\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTANITA body analysis scale MC-780MA (TANITA Europe B.V., Amsterdam, the Netherlands)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDonor/Recipient\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eVital signs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBlood pressure, heart rate, oxygen saturation, temperature, respiratory rate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eStandard clinical measurement devices\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDonor/Recipient\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSpirometry\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGlucose utilization, acid load, resting metabolic rate and oxygen utilization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIndirect calorimetry (PhysiCal, Deutsche Gesellschaft f\u0026uuml;r Ern\u0026auml;hrung und Sport, Feldkirchen-Westerham, Germany)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDonor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eKetone bodies\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026szlig;-ketones in capillary blood, \u0026szlig;-ketones in urine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSelf-tested by GlucoMen aero \u0026szlig;-ketone sensor (A. Menarini diagnostics, Florence, Italy), ketostix test strips, (Bayer AG, Leverkusen, Germany)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDonor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFeasibility\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWellbeing, limitations due the diet, hunger, saturation, health-related quality of life, quality of recovery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePhone call questionnaire, diet diary,\u003c/p\u003e\n \u003cp\u003eSF-12 questionnaire(32), QoR-15- questionnaire (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDonor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAdverse events\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIncidence, frequency and severity of adverse events\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePhone call questionnaire,\u003c/p\u003e\n \u003cp\u003eData extraction from medical records, CTCAE-criteria\u0026nbsp;(35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDonor/Recipient\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePre-existing diseases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eChronic kidney disease, chronic cardiovascular disease, chronic liver disease, chronic pulmonary disease, autoimmune disorder, malignancy, Solid Organ Transplantation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eData extraction from medical records\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDonor/Recipient\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePre-existing medication\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDrug, start / stop relative to the day of transplantation, dosage, administration, frequency, adverse event\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eData extraction from medical records\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDonor/Recipient\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAnesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMode of anesthesia, catheter, inotropic support, pre- and intraoperative fluid administration, intraoperative vital signs, complications during anesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eData extraction from medical records\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDonor/Recipient\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSurgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eOperation time, warm ischemia duration, cold ischemia duration, bleeding event, surgical complication\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eData extraction from medical records\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDonor/Recipient\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePostoperative clinical\u003c/p\u003e\n \u003cp\u003eCourse\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAdmission / duration ICU, readmission to ICU, treatment at ICU, duration inotropic support, fluid input, urine output, vital signs, postoperative medication\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eData extraction from medical records\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDonor/Recipient\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLaboratory measurements I\u003c/p\u003e\n \u003cp\u003eLaboratory measurements II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSerum creatinine, cystatin c, BUN, eGFR, serum alpha-1 microglobulin, uric acid, serum sodium, serum potassium, serum chloride, serum magnesium, LDH, CK, AST, ALT, bilirubin, g-GT, triglycerides, cholesterol (HDL, LDL), leukocytes, platelets, hemoglobin, c-reactive protein, proteinuria, alpha-1 microglobulin in urine, urine creatinine, urine sodium, urine potassium, urine chloride, urine magnesium\u003c/p\u003e\n \u003cp\u003eAmino acids in blood and urine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAnalyzed in the DIN ISO 15189:2014-accredited central laboratory of the University Hospital of Cologne using standard clinical assays\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDonor/Recipient\u003c/p\u003e\n \u003cp\u003eDonor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTissue collection and biobanking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e24-hour urine collection, stool samples, kidney biopsy, perirenal fatty tissue, kidney vessels\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDirectly snap frozen in liquid nitrogen in the OR,\u0026nbsp;stored at -80 \u0026deg;C-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDonor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eOutcome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTime of hospitalization, incidence of AKI,\u003c/p\u003e\n \u003cp\u003eacute transplant rejection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eData extraction from medical records, KDIGO classification\u0026nbsp;(36),\u003c/p\u003e\n \u003cp\u003eBanff classification\u0026nbsp;(37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDonor/Recipient\u003c/p\u003e\n \u003cp\u003eRecipient\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: AKI = acute kidney injury, AST = aspartate aminotransferase, ALT = alanine aminotransferase, BMI = body mass index, BUN = blood urea nitrogen, CK = creatine kinase, CTCAE = common terminology criteria of adverse events ,eGFR=estimated glomerular filtration rate, g-GT = gamma-glutamyl transferase, HDL = high density lipoprotein, HIV/AIDS = human immunodeficiency virus/acquired immune deficiency syndrome, ICU = intensive care unit, KDIGO = kidney diseases improving global outcomes, LDH = lactate dehydrogenase, LDL = low density lipoprotein, OR = operation Room, QoR-15 = quality of recovery-15 questionnaire, RNA = ribonucleotide acids, SF-12 = short-form-healthy-survey- 12.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDietary regimens\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFasting Mimicking Diet (FMD)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCaloric intake is restricted by using an FMD for five days prior to the planned living kidney donation, as previously described (Figure 1, Table 1) (38, 39). Briefly, FMD consists of a plant-based fasting program (ProLon\u003csup\u003e\u0026reg;\u003c/sup\u003e, L-Nutra, Berlin, Germany). Thus, the diet contains 1100 kcal (4600 kJ) with a proportion of 11% protein, 46% fat and 43% carbohydrates on the first day. From the second day onwards, the caloric intake is further reduced to 715 kcal (3000 kJ) with 9% protein, 44% fat and 47% carbohydrates. FMD is prepared daily by the patient at home according to instructions given by the manufacturer.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eKetogenic diet (KD)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants in this group consume an isocaloric ketogenic diet (KD) for seven days before the planned living kidney donation (Figure 1, Table 1). To standardize food intake, KD is carried out using a formula diet. According to the respective patient-specific energy requirements, KD is individually prepared by the DILKID-staff. First, the basal metabolic rate (BMR) is calculated using the Mifflin St. Joer formula (Table 3) (40). The individual daily energy turnover (ET, [kcal/d]) corresponds to the product of the BMR with the activity factor (AF) (Table 3). Based on this calculation, the proportionate composition of the diet components is individually adjusted to match each participant\u0026rsquo;s ET. The ketogenic diet consists of three different components. The main component is a very high-fat, low-carbohydrate diet (KetoCal 4:1 neutral, Nutricia Milupa GmbH, Erlangen, Germany). Additional protein substitution is provided by K-AM and Fortimel diet (both Nutricia Milupa GmbH, Erlangen, Germany) as calculated based on the individual patient-specific requirements. All these diets are provided as powders facilitating maximum standardization of a patient-specific formula diet. Aiming for an easy and feasible everyday handling, all components are mixed and packaged as a daily ration. Thus, the respective daily portions will be mixed to a formula diet with water by the recipient at home. The ketogenic diet ensures an isocaloric calorie intake consisting of 80% fats (\u0026gt;125g/day), 15% proteins (\u0026lt;100g/day) and 5% carbohydrates (\u0026lt;20g/day).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: Mifflin St. Joar formula and activity factory definition\u003c/strong\u003e:\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"623\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMifflin St. Joar formula BMR, [kcal/d]):\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eBMR♀ [kcal/d]:\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9.99 x weight + 6.25 x height \u0026ndash; 4.92 x age - 161\u003c/p\u003e\n \u003cp\u003eBMR♂ [kcal/d]:\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9.99 x weight + 6.25 x height \u0026ndash; 4.92 x age \u0026ndash; 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eActivity factory\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eAF 1.2: none or minimal physical activity\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(seating, lying)\u003c/p\u003e\n \u003cp\u003eAF 1.375: light minimal physical activity\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(walking for 2h/d)\u003c/p\u003e\n \u003cp\u003eAF 1.55: moderate physical activity\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(walking for 3h/d)\u003c/p\u003e\n \u003cp\u003eAF 1.725: heavily physical activity\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(walking for 4h/d)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: Age = in years, BMR = basal metabolic rate, height = centimeter (cm), weight = kilogram (kg).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLow intake of sulfur containing amino acids (SAA)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe limit intake of the sulfur-containing amino acids methionine and cysteine is ensured by the formula diet XMET XCYS Maxamaid (Nutricia Milupa GmbH, Erlangen, Germany) for seven days. The calculation of the individual diet intake per day is carried out as described in Table\u0026nbsp;3. To ensure an adequate supply of fat and energy, Fortimel powder, Calogen and DuoCal powder (all Nutricia Milupa GmbH, Erlangen, Germany) are added in an individual, patient-specific manner. Again, the various components are packed together as a daily ration and mixing the diet-powder with water results in a formula diet. Of note, neither the total amount of protein nor the daily calorie intake is restricted in this diet, as only SAA are restricted to 10% of the recommended intake. The participant follows the diet for a total of seven days before the planned living kidney donation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eControl group (CG)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants assigned to the control group receive a balanced, isocaloric, moderate protein, low fat and high carbohydrate diet for seven days before the planned transplantation (41). For reasons of standardization, the diet is based on the Fortimel formula diet (Nutricia Milupa GmbH, Erlangen, Germany). The individually required amount is calculated as above (Table\u0026nbsp;3). The diet is packed into daily portions by the DILKID-staff and the formula diet is achieved by mixing the diet-powder with water.\u003c/p\u003e\n\u003cp\u003eTo ensure sufficient salt intake (5 g/day) during the diets, the participants of KD, SAA and CG will take an additional 200ml of drinking bouillon daily. For each dietary regimen, only calorie-free drinks such as water, black coffee or unsweetened tea may be consumed in addition to the diet. Adherence and possible violations of the diet in the form of additional foods intake is documented by the patient in the diet diary daily (Supplementary File 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Collection and management\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData collection will occur at different times during the DILKID-Trial (Table 1): before, during and after the respective dietary interventions. Data is collected from both donors and recipients. Patient-related data will be also extracted from medical record systems. A detailed overview of all data categories, including measurement methods, is provided in Table 2. The data collected will be directly saved in pseudonymized form by qualified personnel in an electronic Case Report Form (eCRF). For programming the eCRF, we used the dedicated software package EFS Leadership 7.0 version 1.2 (Questback GmbH, Cologne, Germany). This software meets all Good Epidemiology Practice (GEP) demands (42). Stored data is only accessible for the DILKID-staff and regular back-ups of entered data are stored on Questback servers in Cologne, Germany.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome measures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBeing an exploratory pilot-study, the DILKID-Trial addresses the following two concise aims: 1) Feasibility, tolerability and safety analyses of dietary preconditioning in the setting of living kidney donation; 2) Recapitulation of the underlying molecular mechanisms of diet-induced organ protection detected in rodents in mankind.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary outcome measures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIntra- and intergroup studies of the following a priori defined criteria have been set to determine the feasibility, tolerability and safety of the respective diets examined in line with the recommendations from pilot study reporting (43, 44).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFeasibility measures\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eRecruitment: Percentage of donor-recipient pairs accepting dietary preconditioning prior living kidney donation of those offered the intervention.\u003c/li\u003e\n \u003cli\u003eDietary adherence as recorded in the diary (Supplementary File 1) paired with the measurement of ketone bodies and metabolites of sulfur metabolism including methionine, cystine, s-sulfocysteine and thiosulfate in the donor\u0026rsquo;s plasma and urine (18, 28, 43).\u003c/li\u003e\n \u003cli\u003eCompletion: Percentage of kidney donors completing dietary preconditioning prior living kidney donation.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTolerability measures\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eDaily self-assessment of general well-being of kidney donor adhering to the diet using an analogue visual rating scale embedded in their diary (Supplementary File 1).\u003c/li\u003e\n \u003cli\u003eRegular telephone calls with the donor assessing general well-being during dietary intervention using a standardized questionnaire (Supplementary File 2).\u003c/li\u003e\n \u003cli\u003eShort Form Health Survey-12 (SF-12) and Quality of Recovery Questionnaire (QoR-15, Supplementary File 3) to assess general quality of life (GQL) pre- and postoperatively (33, 45).\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eSafety measures\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eIdentification of safety-related changes in liver and kidney function, protein and fat metabolism as quantified by clinical laboratory parameters (Table 2).\u003c/li\u003e\n \u003cli\u003eAssessment of adverse events, including the postoperatively clinical course after living kidney donation in both donor and recipient (Table 2).\u003c/li\u003e\n \u003cli\u003eExamination of kidney graft function as quantified by creatinine, blood urea nitrogen (BUN), cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney molecule-1 (KIM-1) monitored in blood samples of the kidney transplant recipient paired with alpha-1-microglobulin, tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 (TIMP-2 x IGFBP-7, Nephrocheck\u003csup\u003eTM\u003c/sup\u003e), and protein levels in recipient\u0026rsquo;s urine.\u003c/li\u003e\n \u003cli\u003eOccurrence of AKI as classified according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria using serum creatine values or urine output after transplantation (36).\u003c/li\u003e\n \u003cli\u003eOccurrence of acute transplant rejection according to the Banff classification (37).\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eProgression criteria\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn line with pilot study reporting the following progression criteria have been set a priori for progressing to a large-scale RCT (43, 44). Thus, high feasibility is defined as completion rate \u0026gt;\u0026nbsp;80%, moderate feasibility as 51\u0026ndash;80%, and low feasibility as \u0026lt; 50%. If neither tolerability- and/or safety-related concerns nor limited dietary adherence are reported, we consider the dietary regimens revealing a completion rate \u0026gt;80% to be feasible for a large-scale RCT. In contrast, diets with a completion rate reaching moderate feasibility call for further investigation of the collected data. The evidence is considered insufficient to justify further proceeding, if the completion rate of a diet shows low feasibility.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSecondary outcome measures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo recapitulate molecular mechanisms of diet-induced kidney protection in mankind, the secondary outcome measures in the DILKID-Trials consist of the intergroup diet-induced differences in the kidney metabolome, transcriptome and proteome as compared to the control diet. In this context, a multi-layered omics approach paired with single nucleus RNA sequencing (snRNAseq) and semiquantitative matrix-assisted laser desorption/ionization mass spectrometry imaging (sqMALDI-MSI) will be applied to collected kidney tissue, as previously described (17, 46-49). Briefly, bulk kidney metabolomics will be examined by liquid chromatography coupled to electrospray ionization tandem mass spectrometry. Bulk transcriptome datasets will be generated using the TruSeq Total RNA platform. Nano-liquid chromatography and mass spectrometry will allow to examine diet-induced changes in the renal proteome. Of note, beneficial dietary interventions alter protein persulfidation (S sulfhydration), an evolutionary conserved post-translational modification of cysteine residues linked to cellular stress-resistance, in model organisms. So, the analysis of diet-induced changes in protein persulfidation established by 4 chloro-7-nitrobenzofurazan (NBF-Cl) labelling will accompany bulk proteomics (18, 50, 51).\u003c/p\u003e\n\u003cp\u003eMore importantly, the susceptibility of the different tubular epithelial cells regarding AKI varies strongly calling cell type specific approaches (13). Therefore, the addition of snRNAseq will allow to generate a human single-cell atlas of diet-induced transcriptome changes recapitulating the cellular complexity of the human kidney (13). sqMALDI-MSI measurements will additionally facilitate to characterize the cell type specific diet-induced metabolic response in the human kidney on a molecular level.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnalysis plan\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDue to the specific objectives of the DILKID-Trial the analysis plan must be divided into the bioinformatic analyses as part of the multi-layered omics approach described below on the one hand, and the statistical analyses of the collected medical data on the other hand. Medical data collected in the eCRF is converted into a SPSS-compliant binary data file. This enables direct statistical univariate and multivariate analysis of both inter- and intragroup differences using the IBM SPSS Statistics software, version 30.0.0 (IBM Corporation, Armonk, NY, USA). Appropriate statistical tests such as analysis of variance (ANOVA) or non-parametric tests such as Wilcoxon rank test are performed to compare intergroup differences, as well as intragroup longitudinal analyses. Thus, the individual groups are further stratified according to sex and age.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBioinformatic analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBriefly for snRNAseq, unique molecular identifiers (UMIs) are mapped to the human reference genome using STAR 2.5.3a and Seurat v3 is used for further downstream analyses, including normalization, scaling, and clustering of nuclei (52). To perform gene ontology and pathway analyses the R package topGO (using the elim algorithm with Fisher exact test) and the R package cluster Profiler (version 3.6.0), using the function enrichKEGG.22 is employed in a cell specific manner. Signaling pathway impact analysis (SPIA) is performed with the SPIA package for R, version 2.30.0,23 following the standard workflow of the manual. Regarding proteomics and persulfidomics, mass-spectrometry raw data is processed with Maxquant using default parameters (53). Maxquant output files will further be processed using Perseus (version 1.5.5.3) and R/Bioconductor (54). sqMALDI-MSI data is acquired at a pixel size of 20 \u0026mu;m (x, y) using a beam scan area of 16 \u0026times; 16 \u0026mu;m. Isotopically \u003csup\u003e13\u003c/sup\u003eC-labeled yeast extracts as well as isotopically \u003csup\u003e13\u003c/sup\u003eC-labeled s-sulfo-DL-cysteine (DLM-8738, Cambridge Isotope Laboratories, Tewksbury, MA, USA) are used as internal standards to ensure cellular specific metabolic quantifications using R as previously described (48).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eDietary preconditioning with CR, FMD and SAA-restricted diets shows great potential in protecting organ function in rodent models of ischemia or drug-induced AKI (15-18). Lacking knowledge of the underlying mechanisms mediating diet-induced organ protection that are conserved in humans paired with the risk of malnourishment in the frail and multimorbid nephrology patients hindered the transfer of this immense potential from bench-to-bedside (4, 5, 22-24).\u003c/p\u003e\n\u003cp\u003eConsequently, we set up the DILKID-Trial to examine these beneficial dietary preconditioning regimens in the context of living kidney donations at the cross-roads of molecular biology, translational nephrology and transplant medicine. Thus, the DILKID-Trial allows to study the feasibility, tolerability and safety of dietary interventions in a controlled academic setting. This is an important goal in translational medicine to justify proceeding to a large-scale RCT following our pre-defined progression criteria and, in turn, will guide on the development of an optimal diet for humans.\u003c/p\u003e\n\u003cp\u003eBesides to feasibility, safety and tolerability analyses of these beneficial diets at hand, DILKID\u0026rsquo;s bio sampling approach facilitates the confirmation of findings from animal models in humans (Figure 1). In this context, the additional use of snRNAseq and sqMALDI-MSI is a very powerful approach that overcomes key limitations of sole bulk-omics approaches. As the susceptibility of the different renal cell types regarding AKI varies strongly, snRNAseq and sqMALDI-MSI enable cell type specific analyses in the context of diet-induced kidney protection in human material (13). These molecular analyses will provide precious information on pharmacological approaches in the future to protect against organ injury in the kidney and beyond. In this context, overlapping diet-induced changes in cysteine metabolism observed in our rodent IRI model may contain novel promising druggable targets in search of renal resilience (Figure 2) (4, 5, 18).\u003c/p\u003e\n\u003cp\u003eThe design of the translational DILKID-Trial comes with several limitations. First, sample size per study arm is small. Thus, also considering the generally excellent outcome in living kidney donation, the efficacy of the interventions is not the primary study endpoint. Second, employing dietary interventions, obviously, comes with the risk of limited dietary adherence, in particular, as dietary preconditioning is performed in an outpatient setting. To face this, telephone and written self-disclosure are used to confirm dietary adherence. More importantly, dietary adherence is additionally confirmed by the analysis of intraindividual changes in measured levels of the SAA cysteine and methionine in both serum and urine, as well as ketone bodies in the FMD and KD groups, respectively. Furthermore, living kidney donors are highly reliable, since they have a high intrinsic motivation towards the success of the intervention through their donation. Of note, all other diets except for FMD are designed as formula diets for maximum standardization paired with an easy everyday handling by the participants to reduce the risk of incorrect intake. Third, the DILKID-personal is not blinded due to individual preparation of the diets at hand. Despite these shortcomings, a major strength of the DILKID-Trial is its design as one of only few randomized-controlled clinical diet studies in transplant medicine to date (5, 25). As a summary, the DILKID-Trial may serve as blueprint when examining dietary and/or nutritional interventions in a controlled academic setting to close the gap from bench to bedside in the context of diet-induced organ protection (55, 56).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe DILKID-Trial is a truly translational pilot RCT at the cross-roads of molecular biology, translational nephrology and transplant medicine. Thus, DILKID may promote the successful transfer of dietary interventions towards the clinical setting, in addition to the identification of novel druggable approaches to protect organ function from damaging stimuli (55, 56). As the beneficial effects of dietary preconditioning are not limited to the kidney, DILKID will provide insights and a useful template for other fields beyond nephrology.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cul\u003e\n \u003cli\u003eAE = adverse events\u003c/li\u003e\n \u003cli\u003eAF = activity factor\u003c/li\u003e\n \u003cli\u003eAKI = acute kidney injury\u003c/li\u003e\n \u003cli\u003eALT = alanine aminotransferase\u003c/li\u003e\n \u003cli\u003eANOVA = analysis of variance\u003c/li\u003e\n \u003cli\u003eAST = aspartate aminotransferase\u003c/li\u003e\n \u003cli\u003eBMR = body mass index\u003c/li\u003e\n \u003cli\u003eBUN = blood urea nitrogen\u003c/li\u003e\n \u003cli\u003eCG = control group\u003c/li\u003e\n \u003cli\u003eCK = creatine kinase\u003c/li\u003e\n \u003cli\u003eCKD = chronic kidney disease\u003c/li\u003e\n \u003cli\u003eCR = calorie restriction\u003c/li\u003e\n \u003cli\u003eCTCAE = common terminology criteria of adverse events\u003c/li\u003e\n \u003cli\u003eD = days\u003c/li\u003e\n \u003cli\u003eDILKID = Dietary Interventions during Living Kidney Donations\u003c/li\u003e\n \u003cli\u003eeCRF = electronic case report form\u003c/li\u003e\n \u003cli\u003eeGFR = estimated glomerular filtration rate\u003c/li\u003e\n \u003cli\u003eET = energy turnover\u003c/li\u003e\n \u003cli\u003eFMD = fasting mimicking diet\u003c/li\u003e\n \u003cli\u003eGDPR = general data protection regulation\u003c/li\u003e\n \u003cli\u003eGEP = good epidemiology practice\u003c/li\u003e\n \u003cli\u003eg-GT = gamma-glutamyltransferase\u003c/li\u003e\n \u003cli\u003eGQL = general quality of life\u003c/li\u003e\n \u003cli\u003eHDL = high density lipoprotein\u003c/li\u003e\n \u003cli\u003eHIV/AIDS = human immunodeficiency virus / acquired immune deficiency syndrome\u003c/li\u003e\n \u003cli\u003eICU = intensive care unit\u003c/li\u003e\n \u003cli\u003eIRI = ischemia-reperfusion injury\u003c/li\u003e\n \u003cli\u003eKD = ketogenic diet\u003c/li\u003e\n \u003cli\u003eKDIGO = kidney diseases improving global outcomes\u003c/li\u003e\n \u003cli\u003eLDH = lactate dehydrogenase\u003c/li\u003e\n \u003cli\u003eLDL = low density lipoprotein\u003c/li\u003e\n \u003cli\u003eNTX = kidney transplantation\u003c/li\u003e\n \u003cli\u003eOR = operation room\u003c/li\u003e\n \u003cli\u003eQoR-15 = quality of recovery 15-questionnaire\u003c/li\u003e\n \u003cli\u003eRCT = randomized controlled trial\u003c/li\u003e\n \u003cli\u003eRNA = ribonucleotide acids\u003c/li\u003e\n \u003cli\u003eSAA = dietary restriction of sulfur-containing amino acids\u003c/li\u003e\n \u003cli\u003eSF-12 = short form health survey-12\u003c/li\u003e\n \u003cli\u003esnRNAseq = single nucleus RNA sequencing\u003c/li\u003e\n \u003cli\u003eSPIA = signaling pathway impact analysis\u003c/li\u003e\n \u003cli\u003eSPIRIT = standard protocol items: recommended for intervention rials\u003c/li\u003e\n \u003cli\u003eSPSS = statistical package for the social sciences\u003c/li\u003e\n \u003cli\u003esqMALDI-MSI = semiquantitative matrix-assisted laser desorption/ionization mass spectrometry imaging\u003c/li\u003e\n \u003cli\u003eUMIs = unique molecular identifiers\u003c/li\u003e\n \u003cli\u003eW = weeks\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe DILKID-Trial has been approved by the Ethics Committee of the Medical Faculty of the University of Cologne (EK 20-1066) and is registered at \u003cem\u003eclinicaltrials.gov\u003c/em\u003e (NCT05709600, date of registration 2023-02-02). DILKID is conducted in accordance with the Declaration of Helsinki and the good clinical practice guidelines of the International Conference on Harmonization.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSC is supported by the Cologne Clinician Scientist Program (CCSP) / Faculty of Medicine / University of Cologne during the conduct of the study. FCK is supported by the Cologne Clinician Scientist Program (CCSP) / Faculty of Medicine / University of Cologne, funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) (Project No. 413543196), reports grant from the Else Kröner-Fresenius-Stiftung, during the conduct of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Department II of Internal Medicine received research funding from Fresenius Kabi outside the submitted work. RUM served as advisor to AICURIS, GSK, Vertex, Alnylam, Santa Barbara Nutrients and Vifor outside the submitted work. FCK reports consulting fees from Atriva Therapeutics GmbH, outside the submitted work. All other authors report no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLK, SC, DS, MT, TW, MK, CK, FCK contribute data acquisition. MRS, KJRHA, VB, FG, RUM, FCK had the research idea. SC, RUM, FCK concepted the study design. FL, AB, GS, BVDB, TJR contribute analyzing techniques. FCK provided funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the study center of the Department II of Internal Medicine at the University Hospital Cologne for their ongoing support.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eFontana L, Partridge L. Promoting health and longevity through diet: from model organisms to humans. Cell. 2015;161(1):106-18.\u003c/li\u003e\n\u003cli\u003eMattison JA, Roth GS, Beasley TM, Tilmont EM, Handy AM, Herbert RL, et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature. 2012;489(7415):318-21.\u003c/li\u003e\n\u003cli\u003eSp\u0026auml;th MR, Koehler FC, Hoyer-Allo KJR, Grundmann F, Burst V, M\u0026uuml;ller RU. Preconditioning strategies to prevent acute kidney injury. F1000Research. 2020;9.\u003c/li\u003e\n\u003cli\u003eKoehler FC, Sp\u0026auml;th MR, Hoyer-Allo KJR, M\u0026uuml;ller RU. Mechanisms of Caloric Restriction-Mediated Stress-Resistance in Acute Kidney Injury. Nephron. 2022;146(3):234-8.\u003c/li\u003e\n\u003cli\u003eKoehler FC, Sp\u0026auml;th MR, Meyer AM, M\u0026uuml;ller RU. Fueling the success of transplantation through nutrition: recent insights into nutritional interventions, their interplay with gut microbiota and cellular mechanisms. Curr Opin Organ Transplant. 2024.\u003c/li\u003e\n\u003cli\u003eSusantitaphong P, Cruz DN, Cerda J, Abulfaraj M, Alqahtani F, Koulouridis I, et al. World incidence of AKI: a meta-analysis. Clinical journal of the American Society of Nephrology : CJASN. 2013;8(9):1482-93.\u003c/li\u003e\n\u003cli\u003eO\u0026apos;Sullivan ED, Hughes J, Ferenbach DA. Renal Aging: Causes and Consequences. Journal of the American Society of Nephrology : JASN. 2017;28(2):407-20.\u003c/li\u003e\n\u003cli\u003eVanholder R, Annemans L, Bello AK, Bikbov B, Gallego D, Gansevoort RT, et al. Fighting the unbearable lightness of neglecting kidney health: the decade of the kidney. Clin Kidney J. 2021;14(7):1719-30.\u003c/li\u003e\n\u003cli\u003eOstermann M, Lumlertgul N, Jeong R, See E, Joannidis M, James M. Acute kidney injury. Lancet (London, England). 2025;405(10474):241-56.\u003c/li\u003e\n\u003cli\u003eRewa O, Bagshaw SM. Acute kidney injury-epidemiology, outcomes and economics. Nature reviews Nephrology. 2014;10(4):193-207.\u003c/li\u003e\n\u003cli\u003eCoca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney international. 2012;81(5):442-8.\u003c/li\u003e\n\u003cli\u003eSee EJ, Jayasinghe K, Glassford N, Bailey M, Johnson DW, Polkinghorne KR, et al. Long-term risk of adverse outcomes after acute kidney injury: a systematic review and meta-analysis of cohort studies using consensus definitions of exposure. Kidney international. 2019;95(1):160-72.\u003c/li\u003e\n\u003cli\u003eScholz H, Boivin FJ, Schmidt-Ott KM, Bachmann S, Eckardt KU, Scholl UI, et al. Kidney physiology and susceptibility to acute kidney injury: implications for renoprotection. Nature reviews Nephrology. 2021.\u003c/li\u003e\n\u003cli\u003eMitchell JR, Verweij M, Brand K, van de Ven M, Goemaere N, van den Engel S, et al. Short-term dietary restriction and fasting precondition against ischemia reperfusion injury in mice. Aging cell. 2010;9(1):40-53.\u003c/li\u003e\n\u003cli\u003eSpath MR, Bartram MP, Palacio-Escat N, Hoyer KJR, Debes C, Demir F, et al. The proteome microenvironment determines the protective effect of preconditioning in cisplatin-induced acute kidney injury. Kidney international. 2019;95(2):333-49.\u003c/li\u003e\n\u003cli\u003eHoyer-Allo KJR, Sp\u0026auml;th MR, Brodesser S, Zhu Y, Binz-Lotter J, H\u0026ouml;hne M, et al. Caloric restriction reduces the pro-inflammatory eicosanoid 20-hydroxyeicosatetraenoic acid to protect from acute kidney injury. Kidney international. 2022;102(3):560-76.\u003c/li\u003e\n\u003cli\u003eSp\u0026auml;th MR, Hoyer-Allo KJR, Seufert L, H\u0026ouml;hne M, Lucas C, Bock T, et al. Organ Protection by Caloric Restriction Depends on Activation of the De Novo NAD+ Synthesis Pathway. Journal of the American Society of Nephrology : JASN. 2023;34(5):772-92.\u003c/li\u003e\n\u003cli\u003eKoehler FC, Fu CY, Sp\u0026auml;th MR, Hoyer-Allo KJR, Bohl K, G\u0026ouml;bel H, et al. A systematic analysis of diet-induced nephroprotection reveals overlapping changes in cysteine catabolism. Transl Res. 2022.\u003c/li\u003e\n\u003cli\u003eAndrianova NV, Jankauskas SS, Zorova LD, Pevzner IB, Popkov VA, Silachev DN, et al. Mechanisms of Age-Dependent Loss of Dietary Restriction Protective Effects in Acute Kidney Injury. Cells. 2018;7(10).\u003c/li\u003e\n\u003cli\u003eAndrianova NV, Zorova LD, Pevzner IB, Popkov VA, Chernikov VP, Silachev DN, et al. Resemblance and differences in dietary restriction nephroprotective mechanisms in young and old rats. Aging. 2020;12(18):18693-715.\u003c/li\u003e\n\u003cli\u003eKoehler FC, Sp\u0026auml;th MR, Hoyer-Allo KJR, M\u0026uuml;ller RU. Mechanisms of Caloric Restriction-Mediated Stress-Resistance in Acute Kidney Injury. Nephron. 2021:1-5.\u003c/li\u003e\n\u003cli\u003eGrundmann F, Muller RU, Reppenhorst A, Hulswitt L, Spath MR, Kubacki T, et al. Preoperative Short-Term Calorie Restriction for Prevention of Acute Kidney Injury After Cardiac Surgery: A Randomized, Controlled, Open-Label, Pilot Trial. J Am Heart Assoc. 2018;7(6).\u003c/li\u003e\n\u003cli\u003eGrundmann F, M\u0026uuml;ller RU, Hoyer-Allo KJR, Sp\u0026auml;th MR, Passmann E, Becker I, et al. Dietary restriction for prevention of contrast-induced acute kidney injury in patients undergoing percutaneous coronary angiography: a randomized controlled trial. Scientific reports. 2020;10(1):5202.\u003c/li\u003e\n\u003cli\u003eOsterholt T, Gloistein C, Todorova P, Becker I, Arenskrieger K, Melka R, et al. Preoperative Short-Term Restriction of Sulfur-Containing Amino Acid Intake for Prevention of Acute Kidney Injury After Cardiac Surgery: A Randomized, Controlled, Double-Blind, Translational Trial. J Am Heart Assoc. 2022;11(17):e025229.\u003c/li\u003e\n\u003cli\u003eJongbloed F, de Bruin RWF, Steeg HV, Beekhof P, Wackers P, Hesselink DA, et al. Protein and calorie restriction may improve outcomes in living kidney donors and kidney transplant recipients. Aging. 2020;12(13):12441-67.\u003c/li\u003e\n\u003cli\u003eRahmel T, Effinger D, Bracht T, Griep L, Koos B, Sitek B, et al. An open-label, randomized controlled trial to assess a ketogenic diet in critically ill patients with sepsis. Science translational medicine. 2024;16(755):eadn9285.\u003c/li\u003e\n\u003cli\u003eKnol MGE, Wulfmeyer VC, M\u0026uuml;ller RU, Rinschen MM. Amino acid metabolism in kidney health and disease. Nature reviews Nephrology. 2024.\u003c/li\u003e\n\u003cli\u003eCukoski S, Lindemann CH, Arjune S, Todorova P, Brecht T, K\u0026uuml;hn A, et al. Feasibility and impact of ketogenic dietary interventions in polycystic kidney disease: KETO-ADPKD-a randomized controlled trial. Cell Rep Med. 2023;4(11):101283.\u003c/li\u003e\n\u003cli\u003eChadban SJ, Ahn C, Axelrod DA, Foster BJ, Kasiske BL, Kher V, et al. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation. 2020;104(4S1 Suppl 1):S11-s103.\u003c/li\u003e\n\u003cli\u003eLentine KL, Kasiske BL, Levey AS, Adams PL, Alber\u0026uacute; J, Bakr MA, et al. KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors. Transplantation. 2017;101(8S Suppl 1):S1-s109.\u003c/li\u003e\n\u003cli\u003eChan AW, Tetzlaff JM, Altman DG, Laupacis A, G\u0026oslash;tzsche PC, Krleža-Jerić K, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158(3):200-7.\u003c/li\u003e\n\u003cli\u003eWirtz MA, Morfeld M, Glaesmer H, Br\u0026auml;hler E. Normierung des SF-12 Version 2.0 zur Messung der gesundheitsbezogenen Lebensqualit\u0026auml;t in einer deutschen bev\u0026ouml;lkerungsrepr\u0026auml;sentativen Stichprobe. Diagnostica. 2018;64(4):215-26.\u003c/li\u003e\n\u003cli\u003eStark PA, Myles PS, Burke JA. Development and psychometric evaluation of a postoperative quality of recovery score: the QoR-15. Anesthesiology. 2013;118(6):1332-40.\u003c/li\u003e\n\u003cli\u003eZaza G, Cucchiari D, Becker JU, de Vries APJ, Eccher A, Florquin S, et al. European Society for Organ Transplantation (ESOT)-TLJ 3.0 Consensus on Histopathological Analysis of Pre-Implantation Donor Kidney Biopsy: Redefining the Role in the Process of Graft Assessment. Transpl Int. 2023;36:11410.\u003c/li\u003e\n\u003cli\u003eCommon Terminology Criteria for Adverse Events (CTCAE) Version 5.0. In: Service USDoHaH, editor. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf2017.\u003c/li\u003e\n\u003cli\u003eKhwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clinical practice. 2012;120(4):c179-84.\u003c/li\u003e\n\u003cli\u003eSolez K, Axelsen RA, Benediktsson H, Burdick JF, Cohen AH, Colvin RB, et al. International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology. Kidney Int. 1993;44(2):411-22.\u003c/li\u003e\n\u003cli\u003eWei M, Brandhorst S, Shelehchi M, Mirzaei H, Cheng CW, Budniak J, et al. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med. 2017;9(377).\u003c/li\u003e\n\u003cli\u003eCaffa I, Spagnolo V, Vernieri C, Valdemarin F, Becherini P, Wei M, et al. Fasting-mimicking diet and hormone therapy induce breast cancer regression. Nature. 2020;583(7817):620-4.\u003c/li\u003e\n\u003cli\u003eMifflin MD, St Jeor ST, Hill LA, Scott BJ, Daugherty SA, Koh YO. A new predictive equation for resting energy expenditure in healthy individuals. The American Journal of Clinical Nutrition. 1990;51(2):241-7.\u003c/li\u003e\n\u003cli\u003eBantle JP, Wylie-Rosett J, Albright AL, Apovian CM, Clark NG, Franz MJ, et al. Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association. Diabetes care. 2008;31 Suppl 1:S61-78.\u003c/li\u003e\n\u003cli\u003eHoffmann W, Latza U, Baumeister SE, Brunger M, Buttmann-Schweiger N, Hardt J, et al. Guidelines and recommendations for ensuring Good Epidemiological Practice (GEP): a guideline developed by the German Society for Epidemiology. European journal of epidemiology. 2019;34(3):301-17.\u003c/li\u003e\n\u003cli\u003eEl-Kotob R, Giangregorio LM. Pilot and feasibility studies in exercise, physical activity, or rehabilitation research. Pilot Feasibility Stud. 2018;4:137.\u003c/li\u003e\n\u003cli\u003eThabane L, Ma J, Chu R, Cheng J, Ismaila A, Rios LP, et al. A tutorial on pilot studies: the what, why and how. BMC Med Res Methodol. 2010;10:1.\u003c/li\u003e\n\u003cli\u003eWare J, Jr., Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Medical care. 1996;34(3):220-33.\u003c/li\u003e\n\u003cli\u003eWu H, Dixon EE, Xuanyuan Q, Guo J, Yoshimura Y, Debashish C, et al. High resolution spatial profiling of kidney injury and repair using RNA hybridization-based in situ sequencing. Nat Commun. 2024;15(1):1396.\u003c/li\u003e\n\u003cli\u003eMcEvoy CM, Murphy JM, Zhang L, Clotet-Freixas S, Mathews JA, An J, et al. Single-cell profiling of healthy human kidney reveals features of sex-based transcriptional programs and tissue-specific immunity. Nat Commun. 2022;13(1):7634.\u003c/li\u003e\n\u003cli\u003eWang G, van den Berg BM, Kostidis S, Pinkham K, Jacobs ME, Liesz A, et al. Spatial quantitative metabolomics enables identification of remote and sustained ipsilateral cortical metabolic reprogramming after stroke. bioRxiv. 2024:2024.10.26.620403.\u003c/li\u003e\n\u003cli\u003eWang G, Heijs B, Kostidis S, Mahfouz A, Rietjens RGJ, Bijkerk R, et al. Analyzing cell-type-specific dynamics of metabolism in kidney repair. Nature metabolism. 2022;4(9):1109-18.\u003c/li\u003e\n\u003cli\u003eZivanovic J, Kouroussis E, Kohl JB, Adhikari B, Bursac B, Schott-Roux S, et al. Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration. Cell metabolism. 2019;30(6):1152-70.e13.\u003c/li\u003e\n\u003cli\u003eHine C, Harputlugil E, Zhang Y, Ruckenstuhl C, Lee BC, Brace L, et al. Endogenous hydrogen sulfide production is essential for dietary restriction benefits. Cell. 2015;160(1-2):132-44.\u003c/li\u003e\n\u003cli\u003eSatija R, Farrell JA, Gennert D, Schier AF, Regev A. Spatial reconstruction of single-cell gene expression data. Nat Biotechnol. 2015;33(5):495-502.\u003c/li\u003e\n\u003cli\u003eCox J, Mann M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nature biotechnology. 2008;26(12):1367-72.\u003c/li\u003e\n\u003cli\u003eTyanova S, Temu T, Sinitcyn P, Carlson A, Hein MY, Geiger T, et al. The Perseus computational platform for comprehensive analysis of (prote)omics data. Nature methods. 2016;13(9):731-40.\u003c/li\u003e\n\u003cli\u003eWoolf SH. The meaning of translational research and why it matters. Jama. 2008;299(2):211-3.\u003c/li\u003e\n\u003cli\u003eUtz PJ, Jain MK, Cheung VG, Kobilka BK, Lefkowitz R, Yamada T, et al. Translating science to medicine: The case for physician-scientists. Science translational medicine. 2022;14(632):eabg7852.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pilot-and-feasibility-studies","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pafs","sideBox":"Learn more about [Pilot and Feasibility Studies](http://pilotfeasibilitystudies.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/PAFS/default.aspx","title":"Pilot and Feasibility Studies","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Organ Protection, Resilience, Transplant, Acute Kidney Injury, Dietary Interventions","lastPublishedDoi":"10.21203/rs.3.rs-7095136/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7095136/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAcute kidney injury (AKI) is a frequent threat in the clinic known for its substantial morbidity and mortality. However, effective therapeutic approaches for AKI are lacking. Specific diets efficiently prevent kidney damage from various stimuli in rodents. Nevertheless, the successful transfer to the patient setting is still lagging behind, since the optimal diet for humans paired with the underlying, but conserved molecular mechanisms remain unknown.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Dietary Interventions during Living Kidney Donations (DILKID)-Trial is a four-arm, investigator-initiated, randomized controlled trial performed in an academic setting during living kidney donation in humans. Three dietary interventions - a fasting-mimicking diet, a reduced intake of sulfur-containing amino acids, and a ketogenic diet are tested against a standard control diet. Apart from feasibility, safety and tolerability analyses of these beneficial diets at hand, human tissue samples and biofluids are collected in the DILKID-Trial. These tissue samples are the essential basis to recapitulate the underlying molecular mechanisms of diet-organ protection observed in rodents to man.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe DILKID-Trial is a truly translational pilot-study at the cross-roads of molecular biology, translational nephrology and transplant medicine. Given their strong protective effects in rodent models of AKI, the beneficial diets examined in the DILKID-Trial may substantially add to our therapeutic armamentarium in the clinic. The molecular analyses will provide important mechanistic insight and indicate therapeutic targets for future pharmacological approaches to protect against kidney injury. As the beneficial effects of dietary preconditioning are not limited to the kidney, the DILKID-Trial is a blueprint for further research in the context diet-induced organ protection in the kidney and beyond.\u003c/p\u003e\n\u003cp\u003eClinicalTrials.gov: NCT05709600, date of registration: 2023-02-02.\u003c/p\u003e\n\u003cp\u003ehttps://clinicaltrials.gov/study/NCT05709600?a=1\u003c/p\u003e","manuscriptTitle":"Dietary Interventions during Living Kidney Donations (DILKID) - an open-label, randomized controlled pilot trial study protocol","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-01 09:28:26","doi":"10.21203/rs.3.rs-7095136/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-12-22T15:35:12+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-20T08:29:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-29T11:04:37+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pilot and Feasibility Studies","date":"2025-07-23T07:59:52+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pilot-and-feasibility-studies","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pafs","sideBox":"Learn more about [Pilot and Feasibility Studies](http://pilotfeasibilitystudies.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/PAFS/default.aspx","title":"Pilot and Feasibility Studies","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4ab48ae6-c4b4-407c-89b8-fdc50201b2a0","owner":[],"postedDate":"September 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-09-01T09:28:26+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-01 09:28:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7095136","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7095136","identity":"rs-7095136","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}