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Cardiorenal biomarkers, canagliflozin and outcomes in DKD

Post-hoc analysis of data from the CREDENCE trial strengthens our understanding of the value of biomarkers in predicting complications in people with type 2 diabetes and diabetic kidney disease, and the value of SGLT2 inhibition in reducing adverse events.

Blood samples in rack

A two-way link between cardiovascular disease and chronic kidney disease (CKD) exists, such that each diagnosis may increase the risk for incidence of the other or, if already established, may exacerbate the other. People with type 2 diabetes and CKD with albuminuria are, consequently, at very high risk for cardiac and renal events. Evidence has emerged that concentrations of several circulating stress biomarkers may predict the onset and progression of CKD in type 2 diabetes, and prognosticate cardiovascular events.

The present study evaluated the effect of canagliflozin on biomarker concentrations, and the potential of each biomarker to predict cardiovascular and kidney outcomes. Data from 2627 participants with diabetic kidney disease treated with canagliflozin 100 mg or placebo in the CREDENCE trial were included in a post hoc analysis.

At baseline, the median (quartiles 1 and 3) concentration of each biomarker (NT-proBNP, high-sensitivity cardiac troponin T, growth differentiation factor-15 and IGFBP7) was generally elevated compared with healthy individuals, and was often comparable to those reported for those with heart failure (HF).

At 1 year, all biomarker concentrations rose by 6% to 29% in the placebo arm, compared with 3% to 10% in the canagliflozin arm. Treatment with canagliflozin modestly reduced the longitudinal trajectory of rise in each biomarker. The 3-year reduction in NT-proBNP was particularly noteworthy, with abnormal concentrations (≥125 ng/L) being recorded for 67.1% of participants receiving canagliflozin compared with 75.7% for placebo (P=0.009).

Baseline concentrations of each biomarker were strongly predictive of cardiac and renal outcomes, including HF and progression of CKD. Among participants with baseline data for all four biomarkers, those with high risk scores (HR, 4.01) and moderate risk scores (HR, 2.39) showed a greater risk for the primary outcome (a composite of end-stage kidney disease, doubling of creatinine level, or renal or cardiovascular death) compared with those with low risk scores.

Moreover, by 1 year, 50% increases in NT-proBNP (HR, 1.11), high-sensitivity cardiac troponin T (HR, 1.86), growth differentiation factor-15 (HR, 1.45) and IGFBP7 (HR, 3.76) were associated with risk of the primary outcome.

The findings strengthen our understanding of the substantial cardiovascular risk in those with type 2 diabetes, the value of biomarkers for prognosticating major complications in these individuals, and the consistent benefit of SGLT2 inhibition in reducing event rates.

The full article can be read here.

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