Dietary Intervention Trial Targeting Metabolic Syndrome After Kidney Transplantation

Study Overview
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Brief Summary
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Kidney transplant recipients (KTR) have a considerably lower life expectancy as compared with the general population, primarily due to a high prevalence of cardiovascular diseases. KTR often develop an unfavourable cardio-metabolic risk profile characterized by weight gain, metabolic syndrome and post-transplantation diabetes mellitus (PTDM). In general, nutrition plays a key role in both the prevention and treatment of these cardio-metabolic derangements. However, in KTR most RCT's with a dietary intervention, failed to show significant improvement in cardio-metabolic health. This at least questions the efficacy of the diets of these intervention, which relied on general or diabetes guidelines, after kidney transplantation. KTR not only face a high cardio-metabolic risk, but also have a high risk for malnutrition and muscle mass depletion. More knowledge is required to determine the optimal diet and macronutrient composition for improvement of the cardio-metabolic risk factors in the context of the high malnutrition risk. In this regard, observational studies point towards the needs for a higher protein intake for better patient outcomes. Therefore, in this study, the investigators will examine if a high-protein, carbohydrate-reduced diet is more effective than a diet in line with the Dutch Dietary Guidelines for improvement of cardio-metabolic risk factors and for improvement of the body composition in KTR.

Official Title
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Dietary Intervention Trial Targeting Metabolic Syndrome After Renal Transplantation

Conditions
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Kidney Transplant; Complications

Intervention / Treatment
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* Other: high-protein, carbohydrate-reduced diet
* Other: Dutch Nutritional Guidelines


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older. Given informed consent. At least 6 months after kidney transplantation. Stable renal function with an estimated glomerular filtration rate (eGFR) > 30 mL/min. Raised systolic blood pressure (≥130 mmHg) and at least two more features of metabolic syndrome: central obesity (waist circumference ≥102 for men and ≥88cm for women), elevated triglycerides (≥ 1.7 mmol/L), reduced HDL-C (< 1.0 mmol/L for men and < 1.3 mmol/L for women) or on drug treatment for reduced HDL, elevated plasma glucose (≥ 5.6 mmol/L) or on drug treatment for elevated glucose9. Approval by nephrologist for participation in the study. Exclusion Criteria: Active medical illness, including rejection of the graft. Psychopathology or serious cognitive impairment. Necessity to follow specific dietary measures for health purposes that conflict with the study diets. Use of insulin or sulfonylurea (SU)-derivates. Language barrier. Pregnancy or lactating. Serum potassium > 5.0 mmol/L that requires dietary measures. Moderate or severe malnutrition (Patient-Generated Subjective Global Assessment (PG-SGA) stage B or C). In this case, patient will be referred to a renal dietician. Participation in other intervention trials.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: high-protein, carbohydrate-reduced diet<br> | Other: high-protein, carbohydrate-reduced diet<br>* the high-protein, carbohydrate-reduced diet will consist of 1.2-1.4 g/kg/d protein, 26-20en% carbohydrates and +/- 50en% fatty acids, with mainly unsaturated fatty acids. This diet consist of mainly unprocessed, fresh nutrient-dense food-products. Ultra-processed foods and alcoholic beverages will be totally avoided. Salt consumption will not exceed 5-6 g/d. The diet is ad libitum and caloric restriction will not be applied. The diet will be followed for 6 weeks.<br>|
| Active Comparator: Dutch Nutritional Guidelines<br> | Other: Dutch Nutritional Guidelines<br>* the diet according to the Dutch Nutritional Guidelines will consist of a protein intake of 0.8-1.0 g/kg/d and 50-60en% carbohydrates, and +/-30en% fatty acids, with restriction of saturated fatty acids <10en%. This diet consist of mainly unprocessed, fresh nutrient-dense food-products. Ultra-processed foods and alcoholic beverages will be totally avoided. Salt consumption will not exceed 5-6 g/d. The diet is ad libitum and caloric restriction will not be applied. The diet will be followed for 6 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic blood pressure | Change in systolic blood pressure (in mmHg) | before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardio-metabolic risk factors (lipids) | change in circulating triglyceride concentrations, low-density lipoprotein cholesterol (LDL-C) and HDL-C (in fasting serum levels) in mmol/L. | before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks) | 
| Cardio-metabolic risk factors (diastolic blood pressure) | Change in diastolic blood pressure (in mmHg) | before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks) | 
| Cardio-metabolic risk factors (waist circumference) | change in waist circumference (WC) in cm | before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks) | 
| Cardio-metabolic risk factors (insulin resistance) | change in insulin resistance measuring by the homeostatic model assessment of insulin resistance (HOMA-IR index, fasting glucose, insulin) | before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks) | 
| Body composition | change in fat and muscle mass measured by multi-frequency bio-electrical impedance analysis (BIA) BMI, weight | before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks) | 
| Anthropometric measures | Change in weight in kilograms | before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks) | 
| Anthropometric measures II | Change in Body Mass Index (BMI) in kilograms per square meter | before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks) | 
| Body composition II | change in fat and muscle mass measured by multi-frequency bio-electrical impedance analysis (BIA) | before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks) | 
| Quality of life (QoL) | change in QoL, 12-item short form health survey (SF-12) | before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks) | 
| Fatigue | change in fatigue (measured by Dutch Checklist Individual Strength (CIS-20) questionnaire) | before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks) | 
| Physical functioning | change in Hand Grip Strength (HSG) | before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks) | 
| Physical functioning II | change in the five time sit to stand (FTSTS) test | before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks) | 
| Nutritional intake | change in nutritional intake measured by a 3-day food diary | before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks) | 
| Nutritional intake II | change in nutritional intake measured by nutritional intake biomarkers from 24-hour urine measurements (sodium, potassium, and urea excretion for calculating the protein intake by use of the Maroni equation) | before and after experimental diet (high-protein, carbohydrate-reduced diet - 6 weeks) / before and after active comparator (Dutch Nutritional Guidelines - 6 weeks) / wash-out period in between (6 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kidney transplantation, metabolic syndrome, high-protein diet, dietary intervention