Could Ketoanalogue-supplemented Low Protein Diet Defer Dialysis in Advanced Diabetic Kidney Disease? (K-DDD)
- Conditions
- CKD Stage 4
- Interventions
- Behavioral: Protein restriction
- Registration Number
- NCT03415074
- Lead Sponsor
- Anemia Working Group Romania
- Brief Summary
This is a prospective single center open label randomized controlled trial aiming to assess the effectiveness and safety of a low protein diet (0.6 g/kg-day, mainly vegetarian) supplemented with ketoanalogues of essential amino-acids (sLPD) as compared to a mild protein restriction (0.8 g/kg-day, MPD) in reducing Chronic Kidney Disease (CKD) progression, with a planned total duration is of 18 months.
Adult diabetic patients with CKD stage 4+ \[estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease 4-variable (MDRD4) formula \<30 mL/min per year\], with stable renal function (historical reduction of eGFR of \< 10 ml/min-year) , proteinuria \> 3g/g creatininuria and good nutritional status (SGA A) will be enrolled.
- Detailed Description
Adult diabetic patients with Chronic Kidney Disease (CKD) stage 4+ (estimated GFR using the Modification of Diet in Renal Disease 4-variable, MDRD4, formula \<30 mL/min per year), with stable renal function (historical reduction of eGFR of \< 10 ml/min-year), proteinuria \> 3g/g creatininuria and good nutritional status (SGA A) will be enrolled. Patients with evidence of active kidney disease (except proteinuria), with indication of etiological or pathogenic treatment, those with poor control of diabetes (HbA1c \>8%), those with uncontrolled high blood pressure (≥155/85 mmHg), those with significant co-morbidities (heart failure, active liver disease, malabsorption, active infections, inflammatory diseases requiring corticosteroids), those with uremic symptoms (pericarditis, digestive disorders ) or malnutrition (SGA B or C, serum albumin \< 3.5 g/dl) will be excluded.
Eligible patients will enter a run-in phase (3 mo), when mild protein restriction (0.8g/kg dry ideal bw) will be initiated and compliance will be evaluated twice monthly.
Those who will prove compliant during the run-in phase and still fulfill the selection criteria will be randomized 1:1 (computer-generated numbers) to receive the low protein diet (0.6 g/kg-day, mainly vegetarian) supplemented with ketoanalogues of essential amino-acids (Ketosteril 1 tb/10 kg dry bw) or to continue the mild protein restriction (0.8 g/kg-day).
The total recommended energy intake is of 30 kcal/kg of ideal dry body weight per day in all patients.
The primary composite endpoint is the need for RRT initiation or a more than 50% reduction in the initial eGFR any time during the assessment phase. The decision to initiate RRT will be made by the Ethical Committee of the Hospital, based on the clinical and laboratory data.
The need for RRT initiation, the quality of life \[assessed by the Short Form-36 (SF-36) Questionnaire\], the decline in GFR and the correction of metabolic complications of CKD \[serum levels of urea, calcium, phosphates, serum parathyroid hormone levels, bicarbonate, potassium\] will be secondary efficacy parameters.
Parameters of nutritional status (SGA, anthropometric and biochemical parameters), compliance to the diet, occurrence of any adverse event and the number of withdrawals will be safety variables.
All the parameters will be assessed at baseline, throughout the intervention phase and at end of the study.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 120
- diabetic patients
- CKD stage 4+ (estimated GFR using the Modification of Diet in Renal Disease 4-variable, MDRD4, formula <30 mL/min per year)
- stable renal function (historical reduction of eGFR of < 10 ml/min-year)
- proteinuria > 3g/g creatininuria
- good nutritional status (SGA A)
- evidence of active kidney disease (except proteinuria)
- indication for etiological or pathogenic treatment
- poor control of diabetes (HbA1c >8%)
- uncontrolled high blood pressure (≥155/85 mmHg)
- significant co-morbidities (heart failure, active liver disease, malabsorption, active infections, inflammatory diseases requiring corticosteroids)
- uremic symptoms (pericarditis, digestive disorders
- or malnutrition (SGA B or C, serum albumin < 3.5 g/dl)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Supplemented low protein diet (sLPD) Protein restriction Protein restriction to a low level (0.6 g/kg-day, mainly vegetarian) + ketoanalogues of essential amino-acids supplementation (Ketosteril 1 tb/10 kg dry bw) Mild protein restriction diet (MPD) Protein restriction Mild restriction in dietary protein intake (0.8 g/kg-day)
- Primary Outcome Measures
Name Time Method CKD progression 15 months Percentage of patients requiring RRT initiation or a more than 50% reduction in the initial eGFR at anytime during the study
- Secondary Outcome Measures
Name Time Method Correction of nitrogen balance monthly up to 15 months Serum urea
Nutritional status - Subjective Global Assessment (SGA) monthly up to 15 months SGA
Serum albumin monthly up to 15 months Serum albumin
Occurence of the adverse events twice-a-month during the run-in phase, weekly for the first month after randomization, every 4 weeks during the next 6 months, and every 3 months up to 15 months Occurence of any adverse event
Middle arm muscular circumference (MAMC) monthly up to 15 months MAMC
Inflammatory status monthly up to 15 months Serum C-Reactive Protein (CRP)
Correction of metabolic acidosis monthly up to 15 months Serum bicarbonate
Correction of calcium metabolism abnormalities monthly up to 15 months Serum calcium
Correction of mineral metabolism abnormalities monthly up to 15 months Serum phosphates
Serum level of intact Parathyroid Hormone (iPTH) monthly up to 15 months iPTH
Tricipital Skin Fold (TSF) monthly up to 15 months TSF
Serum cholesterol monthly up to 15 months Serum cholesterol
Compliance to the protein intake twice-a-month during the run-in phase, weekly for the first month after randomization, every 4 weeks during the next 6 months, and then every 3 months up to 15 months Achieved protein intake (urinary urea excretion, Mitch-Maroni's formula)
Compliance to the energy intake twice-a-month during the run-in phase, weekly for the first month after randomization, every 4 weeks during the next 6 months, and then every 3 months up to 15 months Achieved energy intake (3-days food dairy)
Need for renal replacement therapy (RRT) 15 months Percentage of patients requiring RRT during the study
Patients' Quality of life at baseline and than every 3 months up to 15 months Patients' Quality of life, assessed by the SF-36 Questionnaire
Decline in eGFR monthly up to 15 months Difference between eGFR at any timepoint and the initial eGFR
Body Mass Index (BMI) monthly up to 15 months BMI
Trial Locations
- Locations (1)
"Dr Carol Davila" Teaching Hospital of Nephrology
🇷🇴Bucharest, Romania