What is the fractional excretion of sodium and in which patients with type 2 diabetes and chronic kidney disease (estimated glomerular filtration rate ≥30 mL/min/1.73 m²) should dapagliflozin be started?

Fractional Excretion of Sodium (FENa) and Dapagliflozin Initiation in Type 2 Diabetes with CKD

What is FENa?

Fractional excretion of sodium (FENa) is a calculated measure that represents the percentage of filtered sodium that is excreted in the urine, used primarily to distinguish prerenal azotemia (typically FENa <1%) from intrinsic acute kidney injury (typically FENa >1%), though this interpretation must account for clinical context including diuretic use, chronic kidney disease, and specific pathophysiologic states. 1

• FENa is calculated as: (Urine Na × Plasma Cr) / (Plasma Na × Urine Cr) × 100
• In most normal subjects, FENa is usually less than 1% but may increase with higher salt intake 1
• A low FENa (<1%) in acutely azotemic patients usually indicates prerenal azotemia responsive to volume repletion, but can also occur in hepatic failure, cardiac failure, acute glomerulonephritis, contrast nephrotoxicity, and occasionally non-oliguric acute renal failure 1
• A FENa >1% typically indicates intrinsic renal injury, but can be seen with volume depletion in patients receiving diuretics or those with chronic renal insufficiency 1

When to Start Dapagliflozin in Type 2 Diabetes with CKD

For patients with type 2 diabetes and chronic kidney disease, dapagliflozin should be initiated when eGFR is ≥20 mL/min/1.73 m² and urinary albumin is ≥200 mg/g creatinine to reduce chronic kidney disease progression, cardiovascular events, and all-cause mortality. 2

Primary Indications Based on Most Recent Guidelines (2022):

• Initiate dapagliflozin when eGFR ≥20 mL/min/1.73 m² AND urinary albumin ≥200 mg/g creatinine 2
• This represents an expansion from the 2021 guidelines, which recommended initiation at eGFR ≥30 mL/min/1.73 m² with albumin >300 mg/g 2
• The updated threshold is based on DAPA-CKD trial data showing clear efficacy and safety for dapagliflozin in patients with eGFR ≥25 mL/min/1.73 m² and albumin-to-creatinine ratio ≥200 mg/g 2

Additional Considerations for Broader Use:

• Dapagliflozin can be initiated for most patients with type 2 diabetes, CKD, and eGFR ≥20 mL/min/1.73 m² even with lower levels of albuminuria or normal albumin excretion 2, 3
• For patients with eGFR <60 mL/min/1.73 m² without significant albuminuria, SGLT2 inhibitors still provide cardiovascular and renal protection 3
• The benefit extends to patients without type 2 diabetes who have CKD, though the relative reduction in albuminuria is smaller in non-diabetic patients 4, 5

Clinical Outcomes Supporting Initiation:

In the DAPA-CKD trial, dapagliflozin reduced the primary composite outcome (≥50% eGFR decline, end-stage kidney disease, or renal/cardiovascular death) by 39% over a median 2.4 years, with consistent benefits regardless of diabetes status. 6, 5

• Dapagliflozin reduced all-cause mortality by 31% 6
• Cardiovascular composite outcomes decreased by 29% 6
• The number needed to treat to prevent one primary outcome event was 19 over 2.4 years 5
• Dapagliflozin slowed eGFR decline by 0.95 mL/min/1.73 m² per year overall, with greater effect in patients with type 2 diabetes (2.26 mL/min/1.73 m² per year) 7
• Albuminuria was reduced by 29.3% overall, with larger reductions in patients with type 2 diabetes (-35.1%) compared to those without (-14.8%) 4

Monitoring and Safety Considerations:

• Continue dapagliflozin even if eGFR falls below initiation threshold during treatment, unless the patient is not tolerating therapy or requires kidney replacement therapy 2
• Expect an acute, reversible eGFR decline of approximately 2-3 mL/min/1.73 m² within the first 2 weeks, which does not require discontinuation 2, 7
• Monitor for volume depletion, though absolute risk is low, especially at lower eGFR levels 2
• Counsel patients on genital hygiene to reduce risk of mycotic infections (6% incidence vs 1% with placebo) 2
• Educate about euglycemic ketoacidosis risk, particularly in insulin-requiring patients; maintain at least low-dose insulin and pause SGLT2 inhibitor during acute illness 2
• Adjust background glucose-lowering agents (insulin or sulfonylureas) as needed to prevent hypoglycemia, though adjustment is generally not required at initiation 2

Critical Pitfall to Avoid:

Do not withhold dapagliflozin based solely on the initial eGFR decline in the first 2 weeks, as this represents expected hemodynamic changes and the long-term renal protective benefits far outweigh this transient effect. 2, 7