Effect of Dialysis-specific Therapeutic Diet on Biochemical Parameters in Dialysis Patients
- Conditions
- End-Stage Kidney Disease
- Interventions
- Other: Dialysis-specific therapeutic diet
- Registration Number
- NCT06377293
- Lead Sponsor
- Far Eastern Memorial Hospital
- Brief Summary
In patients with kidney failure, disturbances in bone turnover, mineral metabolism, vascular calcification, uremia, inflammation, immunity, metabolomics, nutrition, and gut microbial metabolites are frequent. Unhealthy diet causes altered mineral metabolism, elevated uremic toxin level, immune dysregulation, metabolic abnormalities, inflammation, protein-energy wasting and dysbiosis. The investigators hypothesize that therapeutic diet intervention reverses these uremic complications and thereby reduces cardiovascular risk in patients with kidney failure. In this study, the investigators crafted 4-week dialysis-specific therapeutic diet to illustrate the clinical implications of therapeutic diet for dialysis patients.
- Detailed Description
In patients with kidney failure, disturbance in bone turnover and mineral metabolism, and nutritional deficiency is prevalent, leading to vascular calcification, uremia, inflammation, immune dysregulation, metabolic alteration, and gut microbial dysbiosis, and these abnormalities are associated with increased risk of fracture, extraskeletal or vascular calcification and cardiovascular mortality. It is well known that an unhealthy diet plays an important role in bone-mineral metabolism, uremia, inflammation, metabolomics, protein-energy wasting, and dysbiosis, and therefore nutritional therapy may help to manage these uremic complications to reduce cardiovascular risk in patients with kidney failure. Importantly, serum biomarkers regarding the above-mentioned abnormalities are acutely and closely related to food intake. To our knowledge, no study to date has examined the multifactorial effects of nutritional intervention on bone turnover, mineral metabolism, vascular calcification, uremia, inflammation, immunity, metabolomics, nutrition, and gut microbial metabolites in dialysis patients.
To examine the beneficial effects of nutritional intervention on clinical outcomes, the investigators crafted the dialysis-specific therapeutic diet which was characterized by adequate calorie and protein amounts, natural food ingredients with a low phosphorus-to-protein ratio, higher portions of plant-based food, and high fiber content. In the previous studies, the investigators found that the therapeutic diet rapidly reversed mineral abnormalities within the 1-week intervention period. Among these changes, reduction in serum phosphate level achieved in 2 days, modifications of intact parathyroid hormone (PTH) and calcium levels in 5 days, and reductions in intact and C-terminal fibroblast growth factor-23 (FGF23) levels in 7 days of therapeutic diet intervention. Although the therapeutic diet tended to change uremic toxin level, neither inflammatory nor nutritional markers changed which may be explained by short duration of intervention. It is of interest to know whether the therapeutic diet has a favorable effect on bone turnover, vascular calcification, and gut microbial dysbiosis. In this continuity planning, the investigators are therefore going to analyze the 4-week diet-induced changes in biomarkers regarding bone turnover, metabolites, vascular calcification, and gut microbial metabolites in addition to the previously assessed mineral metabolism, uremia, inflammation, immunity, and nutrition in dialysis patients.
This project aims to explore the multiple diverse effects of dialysis-specific healthy diet on the changes of bone turnover, mineral metabolism, vascular calcification, uremia, inflammation, immunity, metabolomics, nutrition, and gut microbial metabolites in dialysis patients. In contrast to the previous approaches, bone biomarkers for both of bone formation and bone resorption, vascular calcification biomarkers, and gut microbial metabolites will be comprehensively examined. Revealing a complex correlation between the nutritional factors and bone turnover, mineral metabolism, vascular calcification, uremia, inflammation, immunity, metabolomics, nutrition, and gut microbial dysbiosis, this project may shed light on understanding of diet-mediated bone-mineral and uremic homeostasis and uncover strategies of nutritional therapy. A better knowledge of diet-induced pathway on human body homeostasis may lead to new strategies for preventing fracture, vascular calcification or cardiovascular disease risk.
It is to conduct a randomized controlled trial with cross-over design at a dialysis unit of tertiary teaching hospital in Northern Taiwan. Subjects with aged older than 20 years, end-stage kidney disease (ESKD) undergoing maintenance dialysis for more than three months, having adequate dialysis and good dietary compliance will be included. Each participant will receive one study meal during the run-in period to give him or her the opportunity to assess whether he or she can successfully complete the study meals over the next 4 weeks, thus excluding participants who do not prefer the dietary intervention. Then, participants will be randomly assigned into two groups: group A and group B. Those in group A will receive study diet for 4 weeks, followed by 16-week washout period and then receive 4-week usual diet. The opposite order of diets will be prescribed in group B. The study meals are prepared in the hospital cafeteria. Dietary compositions of the study diets were analyzed before the start of the study. The study outcome measures are difference in change-from-baseline values of abnormal mineral metabolism, altered bone turnover, vascular calcification, uremic toxin production, immune dysregulation, metabolite alteration, nutrition, inflammation and gut microbial metabolites between the therapeutic diet and the usual diet.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 50
- Subjects with aged older than 20 years
- End-stage kidney disease (ESKD) undergoing maintenance dialysis for more than three months
- Must have adequate dialysis
- Good dietary compliance
- Serum albumin level less than 2.5 g/dL
- Hospitalization within the past 4 weeks
- Prebiotics, probiotics, symbiotics or antibiotics use within the past 4 weeks
- History of psychiatric disorders
- Having mental retardation
- Those who dislike of the study meals
- Soft diet requirement
- Vegetarian
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Study diet Dialysis-specific therapeutic diet 4-week therapeutic diet intervention as experimental group
- Primary Outcome Measures
Name Time Method Concentrations of intact fibroblast growth factor 23 (pg/mL) 4 weeks Difference in change-from-baseline intact fibroblast growth factor 23 (pg/mL) between therapeutic diet and usual diet
- Secondary Outcome Measures
Name Time Method Concentrations of phosphate (mg/dL) 4 weeks Difference in change-from-baseline phosphate (mg/dL) between therapeutic diet and usual diet
Concentrations of calcium (mg/dL) 4 weeks Difference in change-from-baseline calcium (mg/dL) between therapeutic diet and usual diet
Concentrations of intact parathyroid hormone (pg/mL) 4 weeks Difference in change-from-baseline intact parathyroid hormone (pg/mL) between therapeutic diet and usual diet
Concentrations of bone-specific alkaline phosphatase (μg/L) 4 weeks Difference in change-from-baseline bone-specific alkaline phosphatase (μg/L) between therapeutic diet and usual diet
Concentrations of procollagen-type 1 N-terminal-propeptide (P1NP) (ng/mL) 4 weeks Difference in change-from-baseline procollagen-type 1 N-terminal-propeptide (P1NP) (ng/mL) between therapeutic diet and usual diet
Concentrations of tartrate resistance acid phosphatase-5b (TRACP-5b) (mIU/ml) 4 weeks Difference in change-from-baseline tartrate resistance acid phosphatase-5b (TRACP-5b) (mIU/ml) between therapeutic diet and usual diet
Concentrations of alkaline phosphatase (ALP) (IU/L) 4 weeks Difference in change-from-baseline alkaline phosphatase (ALP) (IU/L) between therapeutic diet and usual diet
Concentrations of free indoxyl sulfate (mg/L) 4 weeks Difference in change-from-baseline free indoxyl sulfate (mg/L) between therapeutic diet and usual diet
Concentrations of free p-cresol sulfate (mg/L) 4 weeks Difference in change-from-baseline free p-cresol sulfate (mg/L) between therapeutic diet and usual diet
Concentrations of pre-albumin (g/dL) 4 weeks Difference in change-from-baseline pre-albumin (g/dL) between therapeutic diet and usual diet
Concentrations of albumin (g/dL) 4 weeks Difference in change-from-baseline albumin (g/dL) between therapeutic diet and usual diet
Concentrations of C-reactive protein (mg/dL) 4 weeks Difference in change-from-baseline C-reactive protein (mg/dL) between therapeutic diet and usual diet
Concentrations of quinolinate 4 weeks Difference in change-from-baseline quinolinate between therapeutic diet and usual diet
Concentrations of mesaconate 4 weeks Difference in change-from-baseline mesaconate between therapeutic diet and usual diet
Absolute number (per μl blood) of CD4+ (cluster of differentiation 4) T cells 4 weeks Difference in change-from-baseline absolute number (per μl blood) of CD4+ (cluster of differentiation 4) T cells between therapeutic diet and usual diet
Absolute number (per μl blood) of CD8+ (cluster of differentiation 8) T cells 4 weeks Difference in change-from-baseline absolute number (per μl blood) of CD8+ (cluster of differentiation 8) T cells between therapeutic diet and usual diet
Absolute number (per μl blood) of monocytes 4 weeks Difference in change-from-baseline absolute number (per μl blood) of monocytes between therapeutic diet and usual diet
Concentrations of fetuin-A (μg/ml) 4 weeks Difference in change-from-baseline fetuin-A (μg/ml) between therapeutic diet and usual diet
Concentrations of trimethylamine-N-oxide (TMAO) (μM) 4 weeks Difference in change-from-baseline trimethylamine-N-oxide (TMAO) (μM) between therapeutic diet and usual diet
Difference in change-from-baseline phosphate-binding equivalent dose (PBED) between therapeutic diet and usual diet 4 weeks The phosphate-binder doses among the study participants will be compared by calculating the phosphate-binding equivalent dose (PBED) values as described by Daugirdas.
Concentrations of C-terminal fibroblast growth factor 23 (RU/mL) 4 weeks Difference in change-from-baseline C-terminal fibroblast growth factor 23 (RU/mL) between therapeutic diet and usual diet