Jardiance (Empagliflozin) and Renal Function
Jardiance provides significant renal protection in patients with chronic kidney disease, slowing disease progression and reducing the risk of kidney failure, and should be continued for cardiovascular and kidney benefits even when eGFR falls below 45 mL/min/1.73 m² until dialysis or transplantation, despite minimal glucose-lowering effects at these levels. 1
Renoprotective Benefits
Empagliflozin demonstrates robust kidney protection across the spectrum of renal function:
In the EMPA-KIDNEY trial involving 6,609 patients with chronic kidney disease (eGFR 20-90 mL/min/1.73 m²), empagliflozin reduced the composite outcome of kidney disease progression or cardiovascular death by 28% (hazard ratio 0.72, P<0.001) compared to placebo over 2 years of follow-up 2
Empagliflozin reduced the risk of incident or worsening nephropathy by 39% and the risk of doubling of serum creatinine accompanied by eGFR reduction by 44% in cardiovascular outcomes trials 1
The annual eGFR decline during chronic treatment was 0.23 mL/min/1.73 m² per year with empagliflozin versus -1.46 mL/min/1.73 m² per year with placebo (P<0.001), representing preservation of kidney function 3
In EMPEROR-Reduced, empagliflozin slowed eGFR decline by 1.11 mL/min/1.73 m²/year in patients with CKD and by 2.41 mL/min/1.73 m²/year in those without CKD 4
Mechanism of Renal Protection
The kidney benefits occur through hemodynamic effects independent of glucose lowering:
Empagliflozin reduces intraglomerular pressure, systemic blood pressure (approximately 4 mmHg systolic and 2 mmHg diastolic), and albuminuria through mechanisms that appear independent of glycemia 1, 5
The drug exhibits both diuretic and natriuretic effects, promoting sodium excretion along with glucose 5
These hemodynamic effects contribute to long-term preservation of kidney function by reducing stress on the glomeruli 3
Dosing Considerations Based on Renal Function
Current guidelines provide specific eGFR thresholds for initiation and continuation:
Initiation: Can be started if eGFR is above 20 mL/min/1.73 m² 1
Continuation: Should be continued for cardiovascular and kidney benefit until dialysis or transplantation, even when eGFR falls below 45 mL/min/1.73 m² 1
Glucose-lowering efficacy: Becomes minimal at eGFR <45 mL/min/1.73 m² and lower, but cardiovascular and renal benefits persist 1
FDA labeling: Use is not recommended when eGFR is persistently less than 45 mL/min/1.73 m² for initiation and is contraindicated in patients with eGFR less than 30 mL/min/1.73 m² 6
Note the discrepancy: The 2025 ADA guidelines recommend continuation and even initiation down to eGFR 20 mL/min/1.73 m² based on recent trial data 1, while FDA labeling remains more conservative 6. The most recent high-quality evidence (EMPA-KIDNEY, 2023) supports the guideline approach 2.
Initial eGFR Changes
Empagliflozin causes predictable hemodynamic changes in kidney function:
On treatment initiation (baseline to week 4), there is an acute decline in eGFR of approximately -0.77 mL/min/1.73 m² per week, representing hemodynamic adjustment rather than kidney injury 3
After drug cessation, eGFR increases and returns toward baseline level (0.56 mL/min/1.73 m² per week), confirming the hemodynamic nature of the initial decline 3
This initial dip should not prompt discontinuation, as it reflects beneficial reduction in intraglomerular pressure 3
Safety Monitoring and Precautions
Renal function requires careful monitoring, particularly in vulnerable patients:
Renal function should be evaluated prior to initiation and monitored periodically thereafter, with more frequent monitoring recommended in patients with eGFR below 60 mL/min/1.73 m² 6
Volume depletion risk: Empagliflozin causes intravascular volume contraction and can precipitate acute kidney injury, particularly in patients with hypovolemia, chronic renal insufficiency, congestive heart failure, or those on concomitant diuretics, ACE inhibitors, ARBs, or NSAIDs 6
Temporary discontinuation: Consider temporarily discontinuing in settings of reduced oral intake (acute illness, fasting) or fluid losses (gastrointestinal illness, excessive heat exposure); monitor for signs and symptoms of acute kidney injury 6
If acute kidney injury occurs, discontinue empagliflozin promptly and institute treatment 6
Clinical Pitfalls to Avoid
Common errors in managing empagliflozin and renal function:
Do not discontinue empagliflozin solely because eGFR falls below 45 mL/min/1.73 m² in patients already taking it—the cardiovascular and renal benefits persist even when glucose-lowering effects diminish 1
Do not misinterpret the initial eGFR decline as kidney injury—this hemodynamic effect is expected and beneficial 3
Do assess volume status carefully before initiation, particularly in elderly patients, those on diuretics, or those with baseline renal impairment 7, 6
Do discontinue during acute illness with vomiting, dehydration, or before scheduled surgery (3-4 days prior) to mitigate risk of volume depletion and diabetic ketoacidosis 1, 6
Additional Renal Considerations
Other kidney-related effects to monitor:
Acute kidney injury has been reported in approximately 1.6% of patients in clinical trials, particularly in the context of volume depletion 7
Serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization have been reported; evaluate and treat promptly if suspected 6
Genital mycotic infections occur in approximately 6% of patients versus 1% on placebo due to persistent glucosuria creating a glucose-rich genitourinary environment 5