Patients with ‘severely’ high albuminuria reap most kidney benefits from canagliflozin
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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.
“Before the demonstration of their benefits for kidney and cardiovascular outcomes, it was clear that SGLT2 inhibitors reduced albuminuria in patients with type 2 diabetes,” Meg Jardine, PhD, of the George Institute for Global Health at the University of New South Wales Sydney, and colleagues wrote. “Albuminuria is a strong predictor of kidney disease progression and cardiovascular disease and, together with eGFR, is the foundation for the Kidney Disease Improving Global Outcomes (KDIGO) kidney disease risk classification system. Consequently, people with higher albuminuria might derive greater absolute benefit from albuminuria-lowering treatments.”
Although research has demonstrated patients with higher levels of albuminuria experience greater kidney benefits from renin-angiotensin system inhibitors, the investigators contended, it remains uncertain whether SGLT2 inhibitors confer similar benefits.
Therefore, they conducted a secondary analysis of the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial and categorized patients into one of three groups based on urine albumin-to-creatinine ratio (UACR; median UACR at baseline, 927 mg/g; eGFR range from 30 mL/min/1.73 m2 to 90 mL/min/1.73 m2).
The primary outcome of the study was the composite of kidney failure (initiation of dialysis for at least 30 days, kidney transplantation or eGFR less than 15 mL/min/1.73 m2 for at least 30 days), a doubling of serum creatinine from baseline sustained for at least 30 days or mortality due to either kidney disease or cardiovascular disease.
After a median follow-up of 2.6 years, researchers observed higher UACR was associated with higher rates of kidney and cardiovascular events; no difference was found between UACR groups regarding the relative benefit of canagliflozin. Similarly, the benefit on cardiovascular outcomes (including mortality and hospitalization for heart failure) did not differ by UACR.
For almost kidney outcomes, however, the researchers found the absolute benefit was greatest in the highest UACR category.
More specifically, the number of primary composite events prevented across ascending UACR categories were 17 (UACR of 1,000 mg/g or less), 45 (UACR of 1,000 mg/g to 2,999 mg/g) and 119 (UACR of at least 3,000 mg/g) per 1,000 participants.
Further, canagliflozin was associated with lower rates of kidney-related adverse events, with a greater relative reduction in higher UACR categories.
“The consistent relative benefit seen across all levels of baseline albuminuria in the CREDENCE and Canagliflozin Cardiovascular Assessment Study (CANVAS) Program trials makes it reasonable to assume that absolute benefits would accrue in those at lower risk if followed for a longer time horizon, as would happen in clinical practice,” Jardine and colleagues wrote. “Taken together, these findings provide treatment options for those with diabetes and nephrotic-range albuminuria. Ongoing SGLT2 inhibitor trials will provide complementary evidence for the effects of SGLT2 inhibitors on kidney and cardiovascular outcomes in those with nondiabetic kidney disease.”
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