Prognostic impact of chronic kidney disease and renal safety of contemporary therapies in patients with heart failure: a real-world analysis
E Tartaglia, N Bonini, M Mantovani, P Trapanese, F Baldisserri, G Bertolini, E Caliano, G Colucci, M Izzi, M Leoni, K Serafini, D A Mei, J F Imberti, M Vitolo, G BorianiAbstract
Background
Chronic kidney disease (CKD) is common in heart failure (HF) and is associated with adverse outcomes. However, its prognostic impact and the effects of contemporary HF therapies—including angiotensin receptor–neprilysin inhibitors (ARNI) and sodium–glucose cotransporter-2 inhibitors (SGLT2i)—on renal function remain insufficiently characterized in real-world practice.
Purpose
To evaluate the association between CKD and adverse outcomes in HF, and to describe longitudinal changes in renal function according to contemporary HF therapy.
Methods
Data were obtained from a single-center observational registry of patients with HF. CKD was defined as baseline estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m²; CKD severity was further classified as no CKD, G3 (30–59) and G4–5 (<30). Multivariable logistic regression identified factors associated with CKD. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of the primary and secondary outcomes by CKD status and severity. The primary outcome was the composite of all-cause death (ACD) or worsening HF (WHF); secondary outcomes were ACD and WHF. Interaction analyses assessed effect modification across predefined clinical subgroups. Longitudinal analyses evaluated serum creatinine trajectories during follow-up in patients treated with ARNI alone vs ARNI+SGLT2i.
Results
A total of 459 HF patients were included (67.6±11.1 years, 23.1% women); 28.5% had CKD. Compared with patients without, those with CKD were older and had higher comorbidity burden, worse functional status and higher natriuretic peptide levels. In multivariable logistic regression, older age and history of atrial fibrillation were associated with CKD, whereas higher left ventricular ejection fraction was inversely associated. After a median follow-up of 478 (IQR 223–1126) days, 88 (17.8%) primary composite events occurred, including 47 (9.5%) ACDs and 57 (11.6%) WHF events. After multivariable adjustment, CKD showed a graded association with risk, increasing with CKD severity; advanced CKD (G4–5) was independently associated with the primary outcome compared with no CKD (HR 5.53, 95% CI 1.31–23.4), whereas earlier stages (G3) showed directionally consistent but non-significant associations (Table 1; Figure 1, Panel A). In interaction analyses, the association between CKD and the primary outcome was stronger in patients ≥65 years and attenuated in those with reduced LVEF and in patients on SGLT2i (P int <0.05). Longitudinal analyses demonstrated stable renal function, supporting the renal safety of contemporary HF therapies (Figure 1, Panel B).
Conclusions
In HF, CKD is associated with worse outcomes, with a clear risk gradient across CKD stages. Contemporary HF therapies were associated with stable renal function during follow-up, supporting their renal safety in real-world practice.