Cardiorenal Biomarkers, Canagliflozin, and Outcomes in Diabetic Kidney Disease: The CREDENCE Trial

Abstract

BACKGROUND: People with type 2 diabetes and albuminuria are at an elevated risk for cardiac and renal events. The optimal biomarkers to aid disease prediction and to understand the benefits of sodium-glucose cotransporter-2 inhibition remain unclear. METHODS: Among 2627 study participants in the CREDENCE trial (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 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. The effect of canagliflozin on biomarker concentrations was evaluated. 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) was assessed. RESULTS: The median (quartiles 1 and 3) concentration of each biomarker was generally elevated: NT-proBNP, 180 ng/L (82, 442 ng/L); high-sensitivity cardiac troponin T, 19 ng/L (12, 29 ng/L); growth differentiation factor-15, 2595 ng/L (1852, 3775 ng/L); and IGFBP7, 121.8 ng/mL (105.4, 141.5 ng/mL). At 1 year, the biomarkers all rose by 6% to 29% in the placebo arm but only by 3% to 10% in the canagliflozin arm (all P <0.01 in multivariable linear mixed-effect models). Baseline concentrations of each biomarker were strongly predictive of cardiac and renal outcomes. When the biomarkers were analyzed together in a multimarker panel, individuals with high risk scores (hazard ratio [HR], 4.01 [95% CI, 2.52–6.35]) and moderate risk scores (HR, 2.39 [95% CI, 1.48–3.87]) showed a higher risk for the primary outcome compared with those with low risk scores. By 1 year, a 50% increase in NT-proBNP (HR, 1.11 [95% CI, 1.08–1.15]), high-sensitivity cardiac troponin T (HR, 1.86 [95% CI, 1.64–2.10]), growth differentiation factor-15 (HR, 1.45 [95% CI, 1.24–1.70]), and IGFBP7 (HR, 3.76 [95% CI, 2.54–5.56]) was associated with risk of the primary outcome. CONCLUSIONS: Multiple cardiorenal stress biomarkers are strongly prognostic in people with type 2 diabetes and albuminuria. Canagliflozin modestly reduced the longitudinal trajectory of rise in each biomarker. Change in the biomarker level in addition to the baseline level augments the primary outcome prediction. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02065791.

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 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.…”

Hypertonietherapie bei Nierenerkrankungen

“…Neben der antihypertensiven Wirkung hat diese Medikamentenklasse zudem eine antiproteinurische und eine harnsäuresenkende Wirkung, sodass SGLT-2i zu den Standardmedikamenten neben ACEi/ARB bei CKD-Patienten gehören. Die Reduktion von kardiovaskulären und renalen Endpunkten dieser Wirkstoffklasse wurde eindrucksvoll in mehreren Studien gezeigt (CREDENCE [31], DAPA-CKD [32], EMPA-KIDNEY [33]). In der Post-hoc-Analyse der DELIVER-Studie, in die Patienten mit Herzinsuffizienz mit erhaltener Ejektionsfraktion (HFpEF) eingeschlossen waren, erwies sich, dass weniger Patienten mit therapieresistenter Hypertonie unter Dapagliflozin das primäre Outcome erreichen (kardiovaskulärer Tod und Verschlechterung der Herzinsuffizienz).…”

Changes in Cardiovascular and Renal Biomarkers Associated with SGLT2 Inhibitors Treatment in Patients with Type 2 Diabetes Mellitus

“…The non-hypoglycemic effects of SGLT2i have been extensively studied and documented in several publications, both in original research and review articles [32][33][34]. In this comprehensive review, we aimed to focus specifically on cardiovascular and renal biomarkers, as a way to provide quantitative insights into biological processes, disease progression and treatment response, and summarize the most recent knowledge on the changes induced by SGLT2i treatment in T2DM patients.…”