Can I add SGLT2 (sodium-glucose cotransporter 2) inhibitors in patients with an estimated glomerular filtration rate (eGFR) of 55 and nephrotic syndrome?

SGLT2 Inhibitors in Nephrotic Syndrome with eGFR 55

Yes, you can add an SGLT2 inhibitor in a patient with eGFR 55 mL/min/1.73 m² and nephrotic syndrome, and this is actually recommended based on current guidelines for diabetic kidney disease with albuminuria.

Guideline-Based Recommendation

SGLT2 inhibitors are specifically indicated for patients with diabetic nephropathy and albuminuria at this level of kidney function. The 2020 KDIGO guidelines recommend treating patients with type 2 diabetes, CKD, and eGFR ≥30 mL/min/1.73 m² with an SGLT2 inhibitor 1. The 2022 ADA standards specify that SGLT2 inhibitors should be used in patients with eGFR below 60 mL/min/1.73 m² with albuminuria of 200 mg/g or higher, independent of HbA1c targets 1.

Specific Drug Selection at eGFR 55

• Empagliflozin can be used at eGFR ≥30 mL/min/1.73 m² without dose adjustment 1
• Dapagliflozin can be used at eGFR ≥20 mL/min/1.73 m² without dose adjustment 1
• Canagliflozin requires dose consideration: maximum 100 mg daily when eGFR is 30-59 mL/min/1.73 m² 1

All three agents have proven cardiovascular and renal benefits in this population 1.

Evidence in Nephrotic Syndrome

A case report demonstrated successful use of an SGLT2 inhibitor (tofogliflozin) in nephrotic syndrome secondary to diabetic nephropathy, reducing urinary protein excretion from 10.8 to 2.6 g/day over 24 weeks while improving edema and metabolic parameters 2. This suggests SGLT2 inhibitors may have therapeutic potential specifically for nephrotic-range proteinuria in diabetic kidney disease.

Critical Safety Considerations Before Initiation

Volume Status Assessment

• Evaluate for hypovolemia before starting therapy 1, 3
• Consider reducing thiazide or loop diuretic doses to prevent volume depletion 1
• Counsel patient on symptoms of volume depletion (lightheadedness, orthostasis, weakness) 1

Infection Risk Management

• Nephrotic syndrome patients may have increased susceptibility to infections due to immunoglobulin losses 4
• SGLT2 inhibitors increase risk of genital mycotic infections (6% vs 1% placebo) 4
• Counsel on proper genital hygiene before initiating therapy 4
• Monitor for urinary tract infections, urosepsis, and pyelonephritis 3

Ketoacidosis Risk

• Temporarily discontinue during prolonged fasting, surgery, or acute illness 1, 3
• Educate patient that ketoacidosis can occur even with blood glucose 150-250 mg/dL 1, 3
• Monitor for symptoms: nausea, vomiting, abdominal pain, weakness 3

Expected Renal Function Changes

A reversible decrease in eGFR may occur within weeks of initiation but is not an indication to discontinue therapy 1. This represents hemodynamic adaptation (reduced glomerular hyperfiltration) rather than kidney injury 5. The long-term effect is kidney protection with reduced risk of:

• Sustained eGFR decline ≥50% 1
• End-stage kidney disease 6
• Doubling of serum creatinine 6

Monitoring Protocol

• Monitor kidney function before initiation and more frequently given eGFR <60 mL/min/1.73 m² 1, 3
• Check for volume depletion symptoms at follow-up 1
• Monitor for genitourinary infections 4
• Continue SGLT2 inhibitor even if eGFR falls below 30 mL/min/1.73 m² unless not tolerated or dialysis initiated 1

Glucose-Lowering Medication Adjustments

If patient is on insulin or sulfonylureas and meeting glycemic targets:

• Reduce sulfonylurea dose by 50% 1
• Reduce basal insulin dose by 20% 1
• This prevents hypoglycemia when adding SGLT2 inhibitor 1, 3

Common Pitfall to Avoid

Do not discontinue SGLT2 inhibitor due to initial eGFR decline 1. This transient decrease reflects beneficial hemodynamic changes (reduced intraglomerular pressure) and long-term kidney protection 5. Only discontinue for severe infections, Fournier's gangrene, or intolerance 4.