Effect of Low Protein Diet on Top of Dapagliflozin on Chronic Kidney Disease in Patients With Type 2 Diabetes Mellitus

Effect of the Low PROtein Diet on Top of DAPAgliflozin and RAASi on the Progression of Chronic Kidney Disease in Patients With Type 2 Diabetes Mellitus

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

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.

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)