Four biomarkers shown to predict the risk of progressive heart and kidney disease in people with type 2 diabetes with diabetic kidney disease

In this study,¹ concentrations of NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity cardiac troponin T, growth differentiation factor-15, and IGFBP7 (insulin-like growth factor binding protein 7) were measured in the 2627 people who participated in the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE). Investigators examined the effect of canagliflozin on biomarker concentrations as well as the prognostic potential of each biomarker on the primary outcome (a composite of end-stage kidney disease [dialysis, transplantation, or a sustained estimated glomerular filtration rate of <15 mL·min⁻¹·1.73 m⁻²], doubling of the serum creatinine level, or renal death or cardiovascular death).

The study showed that baseline concentrations of each biomarker were strongly predictive of cardiac and renal outcomes. When the biomarkers were analysed together in a multimarker panel, individuals with high and moderate risk scores showed a higher risk for these outcome compared with those with low risk scores. By 1 year, a 50% increase in these biomarkers was associated with increased risk of the primary outcomes. Use of canagliflozin reduced the rise in each biomarker compared with placebo. A major limitations of the analysis however is that not all study participants in the trial had available samples for biomarker measurement. In addition, missing biomarker values during follow up may limit robust interpretation of the analysis. Nonetheless findings from this analysis provides some evidence and rationale to investigate the clinical utility of additional biomarkers as independent predictors of adverse cardiac and renal outcomes. In addition to providing individualized intensive treatment options to high risk patients, it may also provide some mechanistic understanding of how this drug class improved cardio-renal outcomes in people with type 2 diabetes and diabetic kidney disease.