Findings of Sodium-Glucose Cotransporter-2 Inhibitor Kidney Outcome Trials Applied to a Canadian Chronic Kidney Disease Population: A Retrospective Cohort Study

Background: The canagliflozin and renal endpoints in diabetes with established nephropathy clinical evaluation (CREDENCE) and dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trials have demonstrated significant kidney benefits with sodium-glucose cotransporter-2 (SGLT2) inhibitors. SGLT2 inhibitors are now standard of care for patients with diabetic kidney disease and have also been shown to be effective in those with albuminuric CKD with or without diabetes.

Objective: We sought to determine how many patients in nephrology care in British Columbia, Canada, would have been eligible for those trials, to compare rates of outcomes, and to estimate cost avoidance arising from widespread use of SGLT2 inhibitors in this cohort.

Study Design: Retrospective cohort study.

Setting: British Columbia, Canada.

Participants: CKD patients followed in the Kidney Care Clinics in British Columbia.

Measurements: We compared the outcomes of kidney failure, sustained estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m, dialysis, transplant, death from any cause, and doubling of serum creatinine. We also compared the composite outcome of kidney failure and doubling of serum creatinine.

Methods: The cohort was derived using a provincial database by combining the inclusion criteria of CREDENCE and DAPA-CKD trials. We included adult patients aged ≥18 years, urine albumin to creatinine ratio (UACR) ≥20 mg/mmol, and eGFR between 25 and 90 mL/min/1.73 m, between April 1, 2014 and March 31, 2017. The primary outcome was compared with the outcomes experienced in the placebo arms of CREDENCE and DAPA-CKD. The composite outcome stratified by eGFR categories were compared in the British Columbia cohort and the CREDENCE trial. Cost avoidance was estimated based on the number needed to treat to prevent one instance of kidney failure.

Results: A total of 17.5% (3138/17 963) of patients were eligible, resulting in a cohort with a mean age of 69.7 years and 38% women. The eGFR slope of the British Columbia cohort was -4.21 ± 0.47 mL/min. The mean eGFR was 37.0 mL/min/1.73 m, median UACR was 55.3 mg/mmol, and use of renin-angiotensin-aldosterone system inhibitors was 56.6%. The British Columbia cohort experienced nearly double the outcomes of kidney failure, death from any cause, and doubling of serum creatinine than the placebo arms of CREDENCE and DAPA-CKD. When stratified by eGFR, the British Columbia cohort and the CREDENCE placebo arm had similar event rates for those with an eGFR <45 mL/min but there were still higher rates of outcome in the greater than 45 mL/min eGFR groups in the British Columbia cohort. Treating the British Columbia cohort with canagliflozin could lead to net cost avoidance of $2.31 million over 2.6 years.

Limitations: The database only captures those referred to the Kidney Care Clinics by nephrologists, which may lead to selection bias of higher risk patients in the British Columbia cohort. The cost avoidance analysis was a limited high-level analysis.

Conclusions: The British Columbia cohort represents a high-risk group in whom implementation of the use of SGLT2 inhibitors may well improve outcomes and reduce health care system costs.