Dapagliflozin in Non-Diabetic Renal Insufficiency
Dapagliflozin is effective and recommended for non-diabetic patients with chronic kidney disease who have an eGFR ≥20 mL/min/1.73 m² and proteinuria (UACR >200 mg/g), as it significantly reduces the risk of kidney disease progression and cardiovascular events. 1, 2
Efficacy in Non-Diabetic CKD
- Dapagliflozin demonstrated significant benefits in the DAPA-CKD trial for non-diabetic CKD patients, with a 50% relative risk reduction in the primary composite kidney outcome (vs. 64% in diabetic patients) 1
- These benefits were consistent across different etiologies of CKD, including glomerulonephritides (57% risk reduction), ischemic/hypertensive kidney disease, and CKD of other causes 1
- The nephroprotective effects appear to be independent of glycemic control, suggesting direct renal benefits 3
- SGLT2 inhibitors can be initiated in most patients with CKD and eGFR ≥20 mL/min/1.73 m² 4, 2
Mechanism of Action in Non-Diabetic CKD
- Dapagliflozin reduces glomerular hyperfiltration by affecting tubuloglomerular feedback, causing afferent arteriole vasoconstriction 3
- This leads to an initial, reversible decline in eGFR followed by long-term stabilization of kidney function 3, 5
- The medication also reduces inflammatory and fibrotic responses in proximal tubular cells, providing additional nephroprotection 3
- These mechanisms work independently of glucose-lowering effects, explaining efficacy in non-diabetic patients 6
Clinical Application
- For non-diabetic patients with CKD and proteinuria (UACR >200 mg/g), add dapagliflozin to background therapy with an ACEI or ARB 4, 2
- In IgA nephropathy specifically, dapagliflozin should be added to ACEI or ARB therapy when proteinuria exceeds 0.5 g/day 4
- Expect an initial reversible decline in eGFR of 3-5 mL/min/1.73 m² in the first 4 weeks, which does not require discontinuation 4, 2
- Continue therapy even if eGFR falls below initiation thresholds unless the patient is not tolerating treatment or requires kidney replacement therapy 4
Important Considerations and Monitoring
- Short-term studies (6 weeks) showed no significant effect on proteinuria in non-diabetic CKD, but long-term trials demonstrated kidney protection 7, 1
- Monitor for potential adverse effects including genital mycotic infections (more common in women), which can be mitigated with daily hygiene measures 4, 2
- Volume depletion may occur, so consider proactive dose reduction of diuretics in high-risk patients 2
- Implement sick day protocols: hold dapagliflozin during acute illness to prevent complications 2
- Dapagliflozin is contraindicated in patients with eGFR <25 mL/min/1.73 m² according to the FDA label 8
Cardiovascular Benefits
- In non-diabetic CKD patients, dapagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure (HR 0.79) 1
- All-cause mortality was also significantly reduced (HR 0.52) in non-diabetic CKD patients 1
- These cardiovascular benefits provide additional rationale for using dapagliflozin in non-diabetic CKD patients, especially those with or at risk for heart failure 4
The evidence strongly supports using dapagliflozin in non-diabetic CKD patients with proteinuria and eGFR ≥20 mL/min/1.73 m², with benefits extending beyond kidney protection to include cardiovascular risk reduction and improved survival.