Does Jardiance (Empagliflozin) affect renal function, specifically causing Impaired renal function?

From the Guidelines

Jardiance (empagliflozin) can affect renal function, but in ways that are often beneficial for many patients, as it provides kidney protection by slowing the progression of chronic kidney disease in patients with type 2 diabetes, as shown in the most recent study from 2022 1. Initially, Jardiance causes a modest, reversible decrease in estimated glomerular filtration rate (eGFR) due to its mechanism of action as an SGLT2 inhibitor, which reduces pressure in the kidneys. However, long-term studies show that Jardiance actually reduces albuminuria and lowers the risk of worsening kidney function over time. This renal protective effect occurs through multiple mechanisms, including reduced hyperfiltration, decreased intraglomerular pressure, improved tubuloglomerular feedback, and reduced inflammation and fibrosis in kidney tissue. Some key points to consider when using Jardiance include:

• It can be started with eGFR >30 mL/min/1.73 m², though pivotal trials for each included participants with eGFR <30 mL/min/1.73 m² and demonstrated benefit in subgroups with low eGFR, as noted in the 2020 expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes 2.
• Regular monitoring of kidney function is recommended when using this medication, especially during the initial treatment period, as stated in the 2020 expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes 2.
• Jardiance requires caution in patients with severely impaired kidney function (eGFR below 30 mL/min/1.73m²) and is not recommended for patients with end-stage renal disease or on dialysis, as indicated in the 2018 acc expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes and atherosclerotic cardiovascular disease 3. Despite these benefits and considerations, the use of Jardiance is recommended to reduce CKD progression and cardiovascular events in patients with an eGFR ≥20 mL/min/1.73 m² and urine albumin ranging from normal to 200 mg/g creatinine, as stated in the 2022 standards of medical care in diabetes 1.

From the FDA Drug Label

JARDIANCE causes intravascular volume contraction [see Warnings and Precautions (5. 1)] and can cause renal impairment [see Adverse Reactions (6. 1)]. There have been postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients receiving SGLT2 inhibitors, including JARDIANCE; some reports involved patients younger than 65 years of age JARDIANCE increases serum creatinine and decreases eGFR. Patients with hypovolemia may be more susceptible to these changes. Renal function abnormalities can occur after initiating JARDIANCE [see Adverse Reactions (6. 1)]. Use of JARDIANCE is not recommended when eGFR is persistently less than 45 mL/min/1.73 m2 and is contraindicated in patients with an eGFR less than 30 mL/min/1. 73 m2 [see Dosage and Administration (2.2), Contraindications (4) and Use in Specific Populations (8.6)].

Yes, Jardiance can affect renal function. It can cause renal impairment, increase serum creatinine, and decrease eGFR. Patients with hypovolemia may be more susceptible to these changes.

• Key points: + Jardiance can cause renal impairment and increase the risk of acute kidney injury. + Renal function should be evaluated prior to initiation of Jardiance and monitored periodically thereafter. + Use of Jardiance is not recommended when eGFR is persistently less than 45 mL/min/1.73 m2 and is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m2 4. + Treatment with Jardiance was associated with increases in serum creatinine and decreases in eGFR 5.

From the Research

Effects of Jardiance on Renal Function

• Jardiance (empagliflozin) has been found to have both positive and negative effects on renal function in patients with type 2 diabetes.
• A study published in 2016 found that empagliflozin reduced the risk of incident or worsening nephropathy, doubling of the serum creatinine level, and initiation of renal-replacement therapy in patients with type 2 diabetes at high risk for cardiovascular events 6.
• Another study published in 2022 found that the use of empagliflozin in patients with type 2 diabetes and moderate to severe chronic kidney disease raised no new safety concerns and may have beneficial effects on the development of hyperkalemia and edema 7.
• However, empagliflozin has also been found to increase the risk of acute renal failure and volume depletion, particularly in patients with severe impaired renal function 8, 9.
• A case study published in 2021 reported a case of severe metabolic acidosis due to Jardiance-induced euglycemic diabetic ketoacidosis, highlighting the potential for empagliflozin to cause renal dysfunction in certain patients 10.

Key Findings

• Empagliflozin has been found to slow the progression of kidney disease and reduce the risk of clinically relevant renal events in patients with type 2 diabetes at high cardiovascular risk 6.
• The safety profile of empagliflozin in patients with impaired kidney function is similar to that reported in the overall trial population 9, 7.
• Empagliflozin may have beneficial effects on the development of hyperkalemia and edema in patients with type 2 diabetes and advanced chronic kidney disease 7.

Considerations for Patients with Renal Impairment

• Patients with severe impaired renal function should be cautious when using empagliflozin, as it may increase the risk of acute renal failure and volume depletion 8, 9.
• Empagliflozin may be used in patients with established cardiovascular disease or heart failure, but caution is required in fragile elderly patients and in patients with severe impaired renal function 9.