Renal Protection with SGLT2 Inhibitors

Efficacy and Mechanisms

• SGLT2 inhibitors reduce intraglomerular pressure and albuminuria, as recommended by the American Diabetes Association, and slow GFR loss through mechanisms independent of glycemia 1, 2
• The use of SGLT2 inhibitors reduces the risk of incident or worsening nephropathy by 39% and decreases the risk of doubling of serum creatinine by 44% 3
• Renal oxidative stress is reduced by more than 50% with the use of SGLT2 inhibitors, providing cardiovascular and renal protection benefits, reducing glomerular pressure, and decreasing hyperfiltration and physical stress on the filtration barrier 2, 4, 5
• SGLT2 inhibitors lead to a reduction in hyperglycemia and improved HbA1c levels (0.5-1.0% reduction), cause weight loss of approximately 1.5-3.5 kg, and lower systolic blood pressure by 3-5 mmHg, as noted by the European Society of Cardiology 6

Monitoring and Safety

• Regular assessment of renal function, especially at treatment initiation, is recommended for all patients on SGLT2 inhibitors, with monitoring of clinical signs of decongestion, and vigilance of renal function and electrolytes, especially at the start of treatment 2, 7
• Patients taking SGLT2 inhibitors should be monitored for changes in renal function, especially at the start of treatment, and healthcare providers should be aware of the potential risks of volume depletion, genital mycotic infections, and euglycemic ketoacidosis 4, 8, 9, 10, 11, 5, 12
• The American Heart Association suggests starting treatment with IV diuretics (furosemide 20-40 mg IV) and adding SGLT2 inhibitors (empagliflozin 10 mg/day) if eGFR ≥20 ml/min/1.73m², considering acetazolamide as an additional inhibitor of the proximal tubule in cases of diuretic resistance 7
• Monitoring should include evaluation of urinary sodium at 2 hours (target: 50-70 mmol/l) 7

Diuretic Therapy

• The European Society of Cardiology and American College of Cardiology recommend the use of SGLT2 inhibitors as part of the sequential nephron blockade in acute heart failure, utilizing different diuretic agents acting on distinct segments of the nephron, to increase the overall diuretic response, overcome adaptive mechanisms causing diuretic resistance, and achieve improved decongestion in acute heart failure 7, 13, 14
• The following diuretics act on distinct segments of the nephron:

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Guideline Recommendations

• The American Diabetes Association, European Society of Cardiology, and Kidney Disease: Improving Global Outcomes (KDIGO) guideline society recommend SGLT2 inhibitors for their anti-inflammatory and antifibrotic effects, which include reducing oxidative stress and inflammation in the kidneys, and significantly reduce the progression of chronic kidney disease, as demonstrated in clinical trials and studies published in reputable medical journals 4, 9, 10, 1, 2
• The Kidney Disease: Improving Global Outcomes (KDIGO) guideline society recommends SGLT2 inhibitors for patients with chronic kidney disease and an estimated glomerular filtration rate (eGFR) of 20 mL/min/1.73 m² or higher, and SGLT2 inhibitors are particularly beneficial in patients with high albuminuria, as supported by evidence from clinical trials and studies published in reputable medical journals 9