Patients with ‘severely’ high albuminuria reap most kidney b
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Adding to existing evidence that shows the benefits of canagliflozin for patients with type 2 diabetes, researchers found those with “severely increased” baseline albuminuria experienced the most protective kidney effects.

The kidney protective effects of renin-angiotensin system inhibitors are greater in people with higher levels of albuminuria at treatment initiation. Whether this applies to sodium-glucose cotransporter 2 (SGLT2) inhibitors is uncertain, particularly in patients with a very high urine albumin-to-creatinine ratio (UACR; more than 3000 mg/g). Researchers examined the association between baseline UACR and the effects of the SGLT2 inhibitor, canagliflozin, on efficacy and safety outcomes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) randomized controlled trial.

The study enrolled 4401 participants with type 2 diabetes, an eGFR of 30 to 90 ml/min per 1.73 m2, and UACR of more than 300 to 5000 mg/g. Using Cox proportional hazards regression, they examined the relative and absolute effects of canagliflozin on kidney, cardiovascular, and safety outcomes according to a baseline UACR of less than 1000 mg/g (n=2348), 1000 to 3000 mg/g (n=1547), and more than 3000 mg/g (n=506). In addition, researchers also examined the effects of canagliflozin on UACR itself, eGFR slope, and the intermediate outcomes of glycated hemoglobin, body weight, and systolic BP.

-- Overall, higher UACR was associated with higher rates of kidney and cardiovascular events. Canagliflozin reduced efficacy outcomes for all UACR levels, with no evidence that relative benefits varied between levels.

-- For example, canagliflozin reduced the primary composite outcome by 24% in the lowest UACR subgroup, 28% in the UACR subgroup between 1000 to 3000 mg/g, and 37% in the highest subgroup.

-- Absolute risk reductions for kidney outcomes were greater in participants with higher baseline albuminuria; the number of primary composite events prevented across ascending UACR categories were 17, 45, and 119 per 1000 treated participants over 2.6 years.

-- Rates of kidney-related adverse events were lower with canagliflozin, with a greater relative reduction in higher UACR categories.

Conclusively, canagliflozin safely reduces kidney and cardiovascular events in people with type 2 diabetes and severely increased albuminuria. In this population, the relative kidney benefits were consistent over a range of albuminuria levels, with greatest absolute kidney benefit in those with an UACR more than 3000 mg/g.