SGLT2 Inhibitors and Acute Renal Function Changes
Yes, SGLT2 inhibitors typically cause an acute, reversible decrease in eGFR of 3-5 mL/min/1.73 m² within the first 4 weeks of initiation, but this is generally not a reason to discontinue therapy. 1, 2
Mechanism of Acute eGFR Reduction
The initial decline in eGFR observed with SGLT2 inhibitors occurs through several hemodynamic mechanisms:
- SGLT2 inhibition reduces sodium reabsorption in the proximal tubule
- This activates tubuloglomerular feedback, causing afferent arteriole vasoconstriction
- The result is a reduction in intraglomerular pressure and hyperfiltration 3
- This hemodynamic effect is similar to, but independent of, renin-angiotensin system inhibitors
Clinical Significance of the Initial eGFR Decline
The acute reduction in eGFR has several important characteristics:
- Typically occurs within the first 4 weeks of therapy 1
- Usually amounts to a 3-5 mL/min/1.73 m² reduction 1
- Is generally reversible upon discontinuation of the medication 4
- Stabilizes over time with continued therapy 1
- Is considered a hemodynamic effect rather than evidence of kidney injury 1
Management Recommendations
Before Initiating SGLT2 Inhibitors
- Assess baseline renal function (eGFR and albuminuria) 2
- Evaluate volume status and risk for hypovolemia 1
- Consider reducing diuretic doses in patients at risk for volume depletion 1, 2
After Initiating SGLT2 Inhibitors
- Monitor renal function but do not discontinue therapy solely due to the initial eGFR decline 1
- Practice Point 3.7.3 from KDIGO guidelines specifically states: "SGLT2i initiation or use does not necessitate alteration of frequency of CKD monitoring and the reversible decrease in eGFR on initiation is generally not an indication to discontinue therapy" 1
- Continue SGLT2 inhibitor even if eGFR falls below the initiation threshold of 20 mL/min/1.73 m², unless not tolerated or kidney replacement therapy is initiated 1
Special Considerations
- Patients with impaired renal function, elderly patients, or those on loop diuretics may be at increased risk for volume depletion 4
- Withhold SGLT2 inhibitors during times of prolonged fasting, surgery, or critical illness 1, 2
- Educate patients about symptoms of volume depletion and when to seek medical attention 2
- The acute eGFR reduction may actually be nephroprotective in the long term by reducing glomerular hyperfiltration 3, 5, 6
Long-term Renal Benefits
Despite the initial eGFR decline, SGLT2 inhibitors have demonstrated significant long-term renal benefits:
- Reduced albuminuria 1, 7
- Slower progression of kidney disease 1
- Reduced risk of worsening albuminuria 7
- Preservation of kidney function over time 1, 5
- Reduced risk of acute kidney injury 5
The initial eGFR decline should be viewed as a marker of the hemodynamic mechanism that contributes to the long-term nephroprotective effects of these medications, rather than as an adverse effect requiring discontinuation.