Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a class of medications used for various conditions. These oral prescription medicines are frequently recommended for individuals with chronic kidney disease (CKD), helping to maintain the health of the kidney’s filtering units, known as glomeruli. SGLT2 inhibitors also play a role in reducing the urine albumin-creatinine ratio, an indicator of kidney damage.
Understanding Kidney Function and Your eGFR
Kidney function involves the process of filtering waste products and excess water from the blood to produce urine. This continuous filtration is carried out by millions of tiny filtering units within the kidneys called glomeruli. These glomeruli work to remove toxins from the blood, helping to maintain the body’s balance.
The efficiency of this filtration process is measured by the estimated Glomerular Filtration Rate (eGFR). This calculation provides an estimate of how well the kidneys are cleaning the blood each minute. An eGFR is typically determined through a blood test that measures the level of creatinine, a waste product from muscle metabolism, or cystatin C. The eGFR calculation also considers factors such as age, sex, height, and weight. A higher eGFR number generally indicates better kidney function; values above 60 mL/min/1.73 m² are generally considered normal, though a sustained eGFR below this for three months or more can indicate chronic kidney disease.
SGLT2 Inhibitors and Kidney Function Guidelines
SGLT2 inhibitor use is guided by specific eGFR thresholds, or “cut-offs,” which indicate the eGFR level below which initiating the medication may not be recommended. The guidelines for SGLT2 inhibitors have evolved, initially focusing on their use in diabetes management and later expanding to include heart failure and kidney disease.
Current recommendations suggest initiating SGLT2 inhibitor therapy for patients with type 2 diabetes and chronic kidney disease when their eGFR is at least 20 mL/min/1.73 m². Once initiated, it is often reasonable to continue the SGLT2 inhibitor even if the eGFR falls below 20 mL/min/1.73 m², provided the medication is tolerated and kidney replacement therapy has not begun. For the treatment of chronic kidney disease, empagliflozin 10 mg may be initiated down to an eGFR of 20 mL/min/1.73 m² and continued until the patient reaches end-stage kidney failure. Canagliflozin can be initiated for diabetic kidney disease down to an eGFR of 30 mL/min/1.73 m².
These eGFR cut-offs are in place for several reasons: primarily efficacy and safety. The glucose-lowering effect of SGLT2 inhibitors diminishes as eGFR decreases, becoming minimal below 30 mL/min/1.73 m². However, the kidney and heart benefits largely persist even in advanced stages of CKD. The safety considerations include minimizing risks such as volume depletion due to increased urination and the rare possibility of diabetic ketoacidosis. While different SGLT2 inhibitors may have slightly varied guidelines, the underlying principle of using eGFR to guide their application remains consistent.
What Happens When eGFR is Below the Recommended Level
When a patient’s eGFR is below the recommended threshold for initiating an SGLT2 inhibitor, or if it drops below the continuation level while on the medication, healthcare professionals evaluate the situation. The medication might not be started or could be discontinued, weighing the potential benefits against any increased risks.
If an SGLT2 inhibitor is not used or is stopped, alternative treatments for underlying conditions, such as diabetes, heart failure, or kidney disease, are considered. Finerenone might be offered for chronic kidney disease, or other glucose-lowering drugs and blood pressure medications could be adjusted. Ongoing monitoring of kidney function is a standard practice for all patients receiving these medications, allowing healthcare providers to track changes in eGFR and adjust treatment plans. Treatment decisions are individualized, made by healthcare professionals in consultation with the patient, considering their overall health and specific circumstances.