Biomarker Panel Can Predict Future Heart, Kidney Disease in Type 2 Diabetes

James Januzzi, MD
Credit: BAIM Institute

A new analysis of data from more than 2600 patients with type 2 diabetes suggests measuring 4 common biomarkers could help predict future risk of cardiovascular and kidney disease.

Leveraging data from the CREDENCE trial, results of the study suggest increased concentrations of N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTn), growth differentiation factor-15 (GDF-15); and insulin-like growth factor binding protein 7 (IGFBP7) was linked to a 4-fold increase in risk of the primary composite outcome, which was made up of multiple kidney issues or cardiovascular death.¹

“High levels of certain biomarkers are indicators of heart and kidney complications and may help predict future risk of disease progression,” said lead author James Januzzi, MD, a cardiologist at Massachusetts General Hospital and director of heart failure and biomarker trials at the Baim Institute for Clinical Research in Boston.² “Treatment with canagliflozin, a sodium glucose co-transporter 2 inhibitor, lowered biomarker levels and reduced the risk of hospitalization for heart failure and other heart complications in people at the highest risk.”

In recent years, with the evolving recognition of the intersection between cardiovascular and nephrotic illness, the field of cardiorenal metabolic care has begun to emerge to address the growing issues posed by the increasing prevalence of type 2 diabetes, chronic kidney disease, and heart failure. Much of this has been driven by revelations surrounding the benefits of SGLT2 inhibitors, including those observed within the Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation (CREDENCE).¹

With this in mind, Januzzi and an international team of investigators launched the current study to assess the prognostic potential of the aforementioned biomarkers for predicting risk for a primary composite outcome of end-stage kidney disease, doubling of the serum creatinine level, renal death, or cardiovascular death. In addition to evaluating the prognostic potential of each biomarker, both individually and in a multimarker panel, investigators planned to assess the effects of canagliflozin use on biomarker levels using multivariable linear mixed-effect models.¹

Limiting their study to CREDENCE participants with measurements of the 4 biomarkers at baseline, investigators included 2627 of the 4401 participants within the trial. Baseline analysis indicated these patients had elevated median concentrations of each biomarker, with NT-proBNP at 180 ng/L (82, 442 ng/L), hs-cTn at 19 ng/L (12, 29 ng/L), GDF-15 at 2595 ng/L (1852, 3775 ng/L), and IGFBP7 at 121.8 ng/mL (105.4, 141.5 ng/mL).¹

When assessing concentrations in a multimarker panel, individuals with high risk scores (hazard ratio [HR], 4.01; 95% Confidence Interval [CI], 2.52–6.35) and moderate risk scores (HR, 2.39; 95% CI, 1.48–3.87) were at a greater risk of the primary outcome relative to their counterparts with lower scores. Further analysis suggested a 50% increase in NT-proBNP (HR, 1.11; 95% CI, 1.08–1.15), hs-cTn (HR, 1.86; 95% CI, 1.64–2.10), GDF-15 (HR, 1.45; 95% CI, 1.24–1.70), and IGFBP7 (HR, 3.76; 95% CI, 2.54–5.56) were associated with risk of the primary outcome at 1 year.¹

When assessing the effects of canagliflozin, investigators pointed out all biomarkers rose by 6 - 29% in the placebo arm but only by 3 - 10% in the canagliflozin arm (all P < .01).¹

“It was reassuring to discover that canagliflozin helped reduce risks the most in people with the highest chances for complications. Future studies are needed to better understand how Type 2 diabetes in conjunction with kidney disease develops and progresses so that we may initiate life-saving therapies earlier, before symptoms of heart and kidney disease have occurred.” Januzzi added.²

References:

1. Januzzi JL, Mohebi R, Liu Y, et al. Cardiorenal Biomarkers, Canagliflozin, and Outcomes in Diabetic Kidney Disease: The CREDENCE Trial. Circulation. 2023;148(8):651-660. doi:10.1161/CIRCULATIONAHA.123.065251
2. Simple blood test may predict future heart, kidney risk for people with type 2 diabetes. American Heart Association. August 21, 2023. Accessed August 22, 2023. https://newsroom.heart.org/news/simple-blood-test-may-predict-future-heart-kidney-risk-for-people-with-type-2-diabetes.