Long-term Effects of the New Nordic Renal Diet in Patients With Moderate Chronic Kidney Disease
Long-term Effects of the New Nordic Renal Diet in Patients With Moderate Chronic Kidney Disease
As Chronic Kidney Disease (CKD) progresses normophosphatemia is maintained by increasing the
 per nephron urinary phosphorus excretion. Clinically, hyperphosphatemia is associated with
 high mortality, vascular calcification, endothelial dysfunction and progression of left
 ventricular hypertrophy. Currently the treatment of hyperphosphatemia is first being
 initiated in stage 5 and consists of dietetic guidance to avoid dietary phosphate and
 treatment with oral phosphate binders. However, studies have shown important side effects to
 phosphate binders in terms of progression of vascular calcifications. Therefore, it might be
 beneficial to start the dietetic treatment with a reduction of dietary phosphate earlier in
 the disease stage.

 The aim of this project is to develop a New Nordic Renal Diet (NNRD) for CKD patients' stage
 3-4 and to examine the long-term effects in a period of 26-weeks. NNRD has a high content of
 vegetable foods, less animal products and more local food items with a lesser content of
 phosphorus.
This study is a randomized controlled trial performed at Department of Nephrology
 Rigshospitalet, Copenhagen Denmark. Sixty patients will be randomized to either 26 weeks on
 the NNRD (intervention) or 26 weeks on their habitual diet (control). The patients will be
 randomized by blinded drawing by lot. The study participants can leave the trial at any time
 during the study period, without any explanation. The investigator can at any time pull a
 patient out of the trial, if there is concern for the patient's safety or if there is a
 breach in terms of following the protocol. The principal investigator is required to document
 and report dropouts from the study.

 The project group has entered a cooperation agreement with Danish chefs. The agreement
 involves that a team consisting of highly talented chefs will create the recipes for the
 intervention. The recipes will be created in close collaboration with the principal
 investigator who will use her expertise within Clinical Nutrition to combine the
 international nutrients guidelines and culinarian experiences. Moreover, the agreement holds
 that they will find the raw materials needed for the recipes and deliver them weekly to the
 patients' homes throughout the study period in packages containing the recipes and raw
 materials. There will be no financial costs for the patients. The patients in the
 intervention group are expected to follow the recipes five days of the week during the study
 period. The final two days of the week, the patients must plan their own meals. However,
 still following the recommended guidelines upon the NNRD whole food approach delivered from
 the principal investigator, who is a phd.-student and also a registered clinical dietitian
 and MSc in clinical nutrition (Nikita Misella Hansen).

 Sample size calculation and statistical analysis:

 The sample size calculation is based on results from previous studies performed by this study
 group. Within 6 months of participating in this study we expect a decrease in eGFR to be
 about 1 ml/min/1.73 m2. This will have no influence on the total amount of 24-h urine
 phosphorus excretion (primary endpoint), as CKD progresses normophosphatemia is maintained by
 increasing the per nephron urinary phosphorus excretion stimulated by an increase in FGF23
 and PTH leading to progressively increasing plasma levels of FGF23 and SHP the
 "phospho-toxicity model hypothesis" to a compensation from PTH and FGF23. In a randomized
 controlled study with a type-1-error risk of 0.05 (alfa, two tailed) and a power of 80%
 (beta) with a standard deviation of 24-h urine phosphorus excretion of 200 mg and a minimum
 clinical relevant difference of 300 mg the study population is estimated to 21 in each group.
 In case of drop-outs we will include 30 participants in each group. Therefore, total number
 of patients to be included in this study is 60.

 Timeline for the study:

 1. Baseline (day 0)

 Written consent will be obtained, randomization will be performed, and the following
 data will be registered:

 -  Patient history: Gender, age, disease history, current medical record, diagnoses

 -  Comorbidities - e.g. cardiovascular diseases, chronic obstructive lung disease,
 diabetes, hyperlipidemia, hypertension

 -  Smoking (years) and alcohol consumption (average per week)

 -  Blood- and urine samples

 -  DEXA-scan and Electrocardiogram (ECG)

 -  Blood pressure

 -  Weight, BMI, hip- and waist circumference

 -  Questionnaires regarding quality of life

 -  Dietary record

 2. Day 14 The patients will be asked to deliver a 24-hour urine sample for measuring
 phosphorus excretion. Furthermore, blood samples will be drawn

 3. Day 30, 60, 90, 120, 150

 Every 4th week during the study period of 26 weeks (a total of 6 times) all patients
 will be evaluated at the Department of Nephrology, University Hospital, Copenhagen.
 During these first 5 visits the following data will be gathered:

 -  24-h urine phosphorus excretion

 -  Blood samples

 -  Blood pressure

 -  Weight, hip- and waist circumference

 4. Once a week Once every week the principal investigator will offer all the patients a
 telephone meeting. Duration of the phone conversation will depend on individual needs,
 but up to 20 minutes per patient/week despite of allocation. The content of these
 conversations will evolve around dietary intake and overall general condition. The
 principal investigator is in close collaboration with the others in the research group
 who are all medical doctors and will discuss any clinical problem if needed.

 5. Day 180 (study completion)

 During the last day of the study period, the patients will be asked to meet at
 Rigshospitalet one more time. Data as on day 30, 60, 90, 120 and 150 will be gathered,
 moreover the following information will be obtained:

 -  DEXA-scan and ECG

 -  Weight, BMI, hip- and waist circumference

 -  Questionnaires regarding quality of life

 -  Dietary record

 6. Follow-up visit Three months after study completion there will be an end-of-trial visit
 with a 24-h urine collection and blood samples
Inclusion Criteria:

 -  Age >18

 -  Estimated glomerular filtration rate (eGFR) 20-45 ml/min

 -  Medically stable for two months prior to study start

 -  Written and verbally information is given

 -  Read, speak and understands Danish

 -  Written consent

 Exclusion Criteria:

 -  Treatment with phosphate binders

 -  Metabolic disorders that requires specific dietary regulation

 -  Treatment with chemotherapy within the past 6 months

 -  Pregnancy and breastfeeding

 -  Food allergies

 -  Vegans