SGLT2 Inhibitors in Glomerular Hyperfiltration (EMPATHY)

This is an interventional treatment trial for Obesity focused on measuring GFR decline, Glomerular hyperfiltration, SGLT2 inhibitors, Residual proteinuria, Obesity Read More

Inclusion Criteria:

1. Male and female ≥ 18 years old;

2. Increased risk of accelerated renal function loss because of absolute or relative hyperfiltration associated with unhealthy obesity or residual proteinuria defined as:

   Unhealthy obesity:

   • BMI >30 kg/m^2 or waist circumference >94 cm in males and > 80 cm in females
   • Metabolic syndrome, defined as the presence of at least three of the following criteria:
   • Blood pressure>140/90 mmHg or controlled blood pressure under current antihypertensive treatment
   • Triglyceride levels >150 mg/dL
   • HDL<40 mg/dL in males <50 mg/dL in females
   • Fasting blood glucose > 100 and <125 mg/dL

   Residual proteinuria:

   • Urinary protein excretion >1g/24-h to <3g/24-h despite RAS inhibitor therapy with ACE inhibitors or ARBs;
   • Blood pressure in recommended targets with or without blood pressure lowering medications;
3. Estimated GFR > 60 ml/min/1.73m^2 (CKD-EPI formula);
4. Female childbearing potential and non-sterile male must agree to use a method of contraception;
5. Written informed consent

Exclusion Criteria:

1. Type 1or 2 diabetic patients;
2. Concomitant treatment with insulin or oral hypoglycemic agents;
3. Nephrotic syndrome of any etiology;
4. Patients with Autosomal Dominant Polycystic Kidney Disease;
5. Symptomatic urinary tract lithiasis or obstruction;
6. Ischemic kidney disease (because of possible excess risk of acute kidney injury upon SGLT2 inhibition associated reduction in sodium pool and kidney perfusion pressure);
7. Rapidly progressive kidney disease defined by impairment of renal function within 2 weeks - 3 months (for the cohort of patients with residual proteinuria only) ;
8. Active systemic autoimmune diseases;
9. Treatment for glomerulopathies or systemic diseases with steroids or any other immunosuppressive agent within one year;
10. Specific contraindication to SGLT2 inhibitor therapy;
11. Heart failure with or without decreased systolic function;
12. Uncontrolled hypertension or symptomatic hypotension;
13. History of malignancy within 5 years of screening;
14. Inability to fully understand the possible risks and benefits related to study participation;
15. If female, the subject is pregnant or lactating or intending to become pregnant before, during, or within 90 days after last dose; or intending to donate ova during such time period;
16. If male, the subject intends to donate sperm while on the study this study or for 90 days after last dose;
17. Alcohol and drug abuse;
18. Participation in another interventional clinical trial within the 4 weeks prior to screening.