Chronic Kidney Diseases, Type 2 Diabetes Mellitus
Conditions
Keywords
chronic kidney disease, low protein diet, nutrition therapy
Brief summary
This is a prospective multicenter randomized controlled trial with a total duration of 36 months aiming to evaluate the effectiveness and the safety of low protein diet on top of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and renin-angiotensin-aldosterone inhibitors (RAASi) in reducing the progression of chronic kidney disease in patients with type 2 Diabetes Mellitus
Detailed description
The KDIGO Diabetes in CKD Guideline (2020) recommends the use of SGLT2i (level 1A) and suggests (level 2C) the prescription of plant protein-based low-protein diet in patients with chronic kidney disease (CKD) and diabetes mellitus (DM). Both interventions have shown synergistic nephroprotective effects, slowing the progression of chronic kidney disease by reducing glomerular hyperfiltration and proteinuria, thus resulting the hypothesis that by combining these two interventions it could be possible to achieve a superior control over the progression of diabetic kidney disease. The nutritional intervention will consist in a mild protein restriction (0.6 g/kg dry ideal body weight) and a total recommended energy intake of 30-35 kcal/kg of ideal dry body weight per day in all patients. The protein intake will be checked through the food diary and calculated based on urea from 24 hours urine collection. The efficacy and safety parameters will be evaluated during follow-up visits at month 1,2,3,6,12 and 18.
Interventions
Dapagliflozin 10 mg once daily
BEHAVIORALLow protein diet
Plant based low protein diet (0.6 g/kg IBW)
Sponsors
Sf Ioan Emergency Clinical Hospital, Nephrology and Dialysis Department, Bucharest, Romania
Dr Carol Davila Teaching Hospital of Nephrology, Nephrology Department, Bucharest, Romania
Carol Davila University of Medicine and Pharmacy
Anemia Working Group Romania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* age\>18 years old * confirmed chronic kidney disease (with eGFR between 60 and 20 ml/min/1.73 m2 and/or proteinuria \>500 mg/g urinary creatinine) and confirmed type 2 Diabetes Mellitus * stable kidney function for at least 12 weeks before enrollment (defined as decrease in eGFR \< 5 ml/min/1.73 m2/year according to KDIGO 2012 guideline) * treatment with ACE/ARBs and/or MRAs for at least 3 months * no previous treatment with SGLT2i * good nutritional status * declared and anticipated good compliance with the prescribed diet * signed informed consent
Exclusion criteria
* eGFR \< 25 ml/min/1.73 m2 * poorly controlled arterial blood pressure (mean BP≥145/85 mm Hg) * class IV NYHA heart failure, recent MACE (less than 6 months) * relevant comorbid conditions (active infections (HBV, HCV, HIV), active neoplasia, digestive diseases with malabsorption, active autoimmune diseases/ immunosuppressive therapy) * ADPKD * kidney transplantation with functional graft * malnutrition: BMI\<18 kg/me, eight loss \>10% during the last 6 months, serum albumin \<3 g/dL * feeding inability (anorexia, nausea)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to the First Occurrence of Any of the Components of the Composite: ≥30% Sustained Decline in eGFR or Reaching ESRD or CV Death or Renal Death | 12 months after randomization | End Stage Renal Disease (ESRD) is defined as: * Sustained eGFR \<15 mL/min/1.73m2 or, * Chronic dialysis treatment or, * Receiving a kidney transplant |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Variation of hemoglobin levels | month 3, 9 and12 after randomization | Difference between hemoglobin at at any timepoint and the initial serum hemoglobin |
| Variation in serum albumin levels | month 3, 9 and12 after randomization | Difference between serum albumin at at any timepoint and the initial serum albumin |
| Variation in CRP levels | month 3, 9 and12 after randomization | Difference between CRP at at any timepoint and the initial CRP |
| Changes in the quality of life | month 3, 9 and12 after randomization | Evaluated by SF-36 questionaire |
| Rate of decline in the estimated Glomerular Filtration Rate | month 3, 9 and12 after randomization | Difference between eGFR at any timepoint and the initial eGFR |
| Variation of albuminuria | month 3, 9 and12 after randomization | Difference between albuminuria at at any timepoint and the initial albuminuria (expressed as albumin to creatinine ratio) |
| Variation of HbA1C | month 3, 9 and12 after randomization | Difference between HbA1C at at any timepoint and the initial HbA1C |
| Variation of serum cholesterol levels | month 3, 9 and12 after randomization | Difference between serum cholesterol at at any timepoint and the initial serum cholesterol |
| Variation of serum bicarbonate levels | month 3, 9 and12 after randomization | Difference between serum bicarbonate at at any timepoint and the initial serum bicarbonate |
| Variation of serum potassium levels | month 3, 9 and12 after randomization | Difference between serum potassium at at any timepoint and the initial serum potassium |
| Variation of serum sodium levels | month 3, 9 and12 after randomization | Difference between serum sodium at at any timepoint and the initial serum sodium |
| Variation of hematocrit levels | month 3, 9 and12 after randomization | Difference between hematocrit at at any timepoint and the initial hematocrit |
| All cause hospitalizations | 12 months after randomization | Percentage of patients who experienced hospitalizations of all cause |
| Variation in body weight | month 3, 9 and12 after randomization | Difference between body weight at at any timepoint and the body weight |
| Variation in BMI | month 3, 9 and12 after randomization | Difference between BMI at at any timepoint and the initial BMI |
| Variation in handgrip strength | month 3, 9 and12 after randomization | Difference between handgrip strength at at any timepoint and the initial handgrip strength |
Other
| Measure | Time frame | Description |
|---|---|---|
| Compliance to carbohydrate intake | month 1, 3, 9 and12 after randomization | Achieved energy intake will be estimated by the 3-day food diary to calculate thecarbohydrates intake |
| Compliance to the energy intake | month 1, 3, 9 and12 after randomization | Achieved energy intake will be estimated using the 3-day food diary to calculate the daily energy intake |
| Compliance to the protein intake | month 1, 3, 9 and12 after randomization | Achieved protein intake will be estimated based on urinary urea excretion, using Mitch-Maroni's formula |
Countries
Romania
Contacts
Primary ContactLiliana Garneata, Professor
Backup ContactElena Cuiban, PhD student
Outcome results
None listed