AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Implementation of Kidney-Protective Therapies and Renal Outcomes in Heart Failure with Diabetic Kidney Disease: A Multicenter Cohort Study
By Hoshika Y, Kubota Y, Nishino T et al.
Background: Heart failure frequently coexists with diabetic kidney disease (DKD), resulting in substantial cardiorenal risk. Current guidelines recommend kidney-protective therapies including renin-angiotensin system inhibitors or angiotensin receptor-neprilysin inhibitors (RASi/ARNI), sodium-glucose cotransporter-2 inhibitors (SGLT2i), mineralocorticoid receptor antagonists (MRA), and glucagon-like peptide-1 receptor agonists (GLP-1RA). However, their association with renal outcomes remains unclear. Objective: To evaluate the utilization of kidney-protective therapies and their association with renal outcomes in patients with heart failure and DKD. Methods: We conducted a multicenter retrospective cohort study of 1,076 hospitalized patients with heart failure, left ventricular ejection fraction (LVEF) ≥40%, and DKD between April 2018 and March 2025 (median age 79 years, 63.3% male). Patients were categorized according to the number of prescribed kidney-protective medication classes (0, 1, 2, or ≥3 therapies). The primary endpoint was major adverse kidney events (MAKE), defined as a sustained ≥40% decline in estimated glomerular filtration rate (eGFR), eGFR <10 mL/min/1.73 m ² , or initiation of maintenance dialysis. The median follow-up duration was 326 days. Cumulative incidence was compared using Gray’s test with all-cause death treated as a competing risk. Multiple-imputation Fine-Gray regression models were used. Results: RASi/ARNI were prescribed in 65.5% of patients, whereas SGLT2i and MRA were underutilized (35.8% and 34.6%, respectively). No patient received a non-steroidal MRA. The distribution of medication classes was: 0 therapies (n=218), 1 therapy (n=370), 2 therapies (n=319), and ≥3 therapies (n=169). Although cumulative incidence curves did not significantly differ among medication-count groups (Gray’s test, P=0.119; Figure 1), multiple-imputation Cox regression analysis demonstrated that prescription of at least one kidney-protective therapy was independently associated with a lower risk of MAKE compared with no therapy (HR 0.64, 95% CI 0.44-0.94, P=0.024). When stratified by specific drug combinations, significant differences in renal outcomes were observed (Gray’s test, P=0.017; Figure 2). In multiple-imputation Cox regression analysis, the combination of RASi/ARNI and SGLT2i was independently associated with a lower risk of MAKE compared with no therapy (HR 0.40, 95% CI 0.21-0.76, P=0.006). Conclusions: Kidney-protective therapies remain underutilized in patients with heart failure and DKD. Prescription of at least one kidney-protective therapy was independently associated with a lower risk of MAKE. Furthermore, the combination of RASi/ARNI and SGLT2i was associated with a lower risk of MAKE compared with no therapy. Further studies are warranted to establish optimal cardiorenal therapeutic strategies.