SGLT2 inhibitors in CKD management

Patients who have proteinuric CKD may benefit from SGLT inhibitors. Two recent trials have shown that SGLT2 inhibitors are useful for patients with or without diabetes: EMPA-KIDNEY and DAPA-CKD. 

 

EMPA-KIDNEY trial recruited 6609 patients with eGFR 20-44 regardless of albuminuria and eGFR 45-89 if ACR was at least 200mg/g. 46% of the enrolled patients had diabetes. Patients were randomly assigned to Empagliflozin 10mg daily or placebo group. During a median of two years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; P<0.001). However, the differences in risk of hospitalization for heart failure or death from cardiovascular causes were not significant. 

 

DAPA-CKD trial recruited 4304 patients with eGFR 25 to 75 mL/min/1.73 m2 and urinary albumin to creatinine ratio of 200 to 5000 mg/g. 67% of patients had diabetes at baseline. Patients were randomly assigned to Dapagliflozin 10mg daily or placebo group. The primary outcome was defined as "sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes." Over a median of 2.4 years, a primary outcome event occurred in 197 of 2152 participants (9.2%) in the dapagliflozin group and 312 of 2152 participants (14.5%) in the placebo group (hazard ratio, 0.61; P<0.001). Specifically, hazard ratio for the composite of death from cardiovascular causes or hospitalization for heart failure was 0.71 (95% CI, P=0.009). 

 

Given the evidence and difference in preventing MACE, CKD pathway guidelines suggested the choice of SGLT2 inhibitors can be based on a patient's diabetes status. 

 

For patients with diabetes, Canagliflozin, Dapagliflozin, and Empagliflozin can be considered.

SGLT2i	eGFR < 30 mL/min/1.73m2	eGFR ≥ 30 mL/min 1.73m2
Canagliflozin	Do not initiate; Consult Nephrology. If already prescribed, may continue 100mg PO daily. Discontinue once on dialysis.	Dosage for outcome reduction start 100 mg PO daily; may increase up to 300mg PO daily for additional A1C control when GFR > 60.
Dapagliflozin	Do not initiate if GFR < 25; Consult Nephrology. If already prescribed, may continue 10mg PO daily. Discontinue once on dialysis.	Approved for use in eGFR ≥ 25. Dosage for outcome reduction is 10 mg PO daily (DKD and/or HFrEF).
Empagliflozin	Not indicated for DKD; use alternative agent if initiating therapy but may continue this agent in patient who are already initiated. May consider: HFrEF Treatment at GFR > 20. Discontinue once on dialysis.	10 mg OD for Organ protection. 25 mg OD for A1C control.

 

For patients without diabetes, Dapagliflozin can be considered while Canagliflozin and Empagliflozin are not indicated.

SGLT2i	eGFR < 30 mL/min/1.73m2	eGFR ≥ 30 and ≤ 60 mL/min 1.73m2
Dapagliflozin	Do not initiate if GFR < 25; Consult Nephrology. If already prescribed, may continue 10mg PO daily. Discontinue once on dialysis.	Approved for use in eGFR ≥ 25. Dosage for outcome reduction is 10 mg PO daily (non diabetic CKD and/or HFrEF).
Canagliflozin	Not indicated for persons with CKD and without Diabetes.
Empagliflozin	Not indicated for persons with CKD and without Diabetes.

 

Reference:

CKD Pathway - Medical Management

Empagliflozin in Patients with Chronic Kidney Disease | NEJM

Dapagliflozin in Patients with Chronic Kidney Disease | NEJM

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