What precautions should be taken when using Jardiance (Empagliflozin) in patients with fluctuating kidney function or impaired renal function?

Precautions for Jardiance in Patients with Fluctuating Kidney Function

Do not initiate Jardiance if eGFR is below 45 mL/min/1.73 m², and discontinue if eGFR falls persistently below this threshold. 1

Renal Function Assessment and Monitoring

Before Starting Jardiance:

• Assess renal function (eGFR) prior to initiation—this is mandatory, not optional 1
• Do not start Jardiance if eGFR <45 mL/min/1.73 m² 1
• Assess volume status and correct any volume depletion before initiating therapy, particularly in patients with existing renal impairment 1

During Treatment:

• Monitor renal function periodically throughout therapy 1
• Discontinue Jardiance if eGFR falls persistently below 45 mL/min/1.73 m² 1
• The key word is "persistently"—a transient dip does not automatically require discontinuation 1

Expected Initial eGFR Changes

Anticipate an early, reversible decline in kidney function:

• Empagliflozin typically causes an initial eGFR decline of approximately 2-3 mL/min/1.73 m² within the first 4 weeks of treatment 2, 3, 4
• This early decline is hemodynamic in nature, related to reduced intraglomerular pressure, and is not harmful 3
• After the initial dip, eGFR stabilizes during chronic treatment, with a significantly slower rate of decline compared to placebo (0.23 vs -1.46 mL/min/1.73 m²/year) 3
• Upon drug cessation, eGFR returns toward baseline levels 3
• This initial decline should not trigger discontinuation unless it is severe or persistent 4

Clinical Situations Requiring Temporary Discontinuation

Consider temporarily discontinuing Jardiance in these high-risk scenarios:

• Acute illness with reduced oral intake or significant fluid losses 1
• Prolonged fasting due to illness or surgery 1
• When initiating or up-titrating ACE inhibitors or ARBs in patients with impaired renal function 5
• Before procedures involving iodinated contrast media 5
• During intercurrent illness that may compromise renal perfusion 5

Volume Status and Hypotension Precautions

Jardiance causes intravascular volume contraction, which poses particular risks in renal impairment:

• Before initiating, assess and correct volume status in patients with renal impairment, elderly patients, those with low systolic blood pressure, and those on diuretics 1
• Monitor for signs and symptoms of hypotension after initiating therapy 1
• Consider reducing diuretic doses if patients develop symptoms of dehydration 5
• Educate patients about symptoms of dehydration and volume depletion 5

Acute Kidney Injury Risk Management

Jardiance-induced volume contraction can precipitate acute kidney injury:

• If acute kidney injury occurs, discontinue Jardiance immediately and treat promptly 1
• In the EMPULSE trial, investigator-reported acute renal failure occurred in 7.7% of empagliflozin patients versus 12.1% of placebo patients, suggesting empagliflozin may actually be protective 2
• Monitor for signs of acute kidney injury, particularly during periods of volume stress 1

Benefits Across the Spectrum of Kidney Function

Empagliflozin provides cardiovascular and renal benefits even in patients with reduced kidney function:

• The cardiovascular benefits (reduction in cardiovascular death or heart failure hospitalization) are consistent in patients with and without chronic kidney disease (eGFR <60 mL/min/1.73 m²) 6
• Benefits extend to patients with eGFR as low as 20 mL/min/1.73 m² 6
• Empagliflozin slows eGFR decline by 1.11 mL/min/1.73 m²/year in patients with CKD and 2.41 mL/min/1.73 m²/year in those without CKD 6
• The drug reduces the risk of composite kidney outcomes (sustained profound eGFR decline, chronic dialysis, or transplant) by approximately 50% regardless of baseline kidney function 6

Ketoacidosis Risk in Renal Impairment

Patients with renal impairment may be at higher risk for ketoacidosis:

• Monitor for signs of ketoacidosis (nausea, vomiting, abdominal pain, malaise, shortness of breath) even when blood glucose is <250 mg/dL 1
• Consider temporarily discontinuing during prolonged fasting, acute illness, or surgery 1
• If ketoacidosis is suspected, discontinue immediately, evaluate, and treat promptly 1

Concomitant Medication Considerations

Use clinical judgment when combining Jardiance with RAAS inhibitors:

• Exercise caution when initiating an SGLT2 inhibitor in patients starting or up-titrating ACE inhibitors or ARBs if renal function is impaired 5
• Monitor renal function and potassium levels within 1 week of starting or escalating RAAS inhibitors 5
• Avoid triple combination of ACE inhibitor, ARB, and mineralocorticoid receptor antagonist due to hyperkalemia risk 5

Common Pitfalls to Avoid

• Do not discontinue Jardiance for a transient, mild eGFR dip in the first 4 weeks—this is expected and hemodynamic 3, 4
• Do not fail to assess volume status before initiation—volume depletion increases risk of acute kidney injury 1
• Do not ignore the "persistently" qualifier—a single eGFR measurement <45 mL/min/1.73 m² does not mandate immediate discontinuation; confirm with repeat testing 1
• Do not withhold Jardiance solely based on moderate CKD—benefits extend to eGFR as low as 20 mL/min/1.73 m² 6