There are no biological markers to predict the onset of acute kidney injury (AKI) in patients with acute decompensated heart failure (ADHF). Liver-type fatty acid-binding protein (L-FABP) levels are markedly upregulated in the proximal tubules after renal ischemia. We investigated whether urinary L-FABP is a suitable marker to predict AKI in ADHF patients.We examined 281 consecutive patients with ADHF. Serum creatinine (Cr) and L-FABP levels were measured at admission and 24 and 48 h after admission.AKI developed in 104 patients (37%). Urinary L-FABP levels at admission were significantly higher in patients with AKI than in those without (33.0 vs. 5.2 μg/g Cr; p < 0.001). Multivariate analysis showed that baseline urinary L-FABP level was an independent predictor of AKI in ADHF patients (odds ratio 1.08, 95% confidence interval 1.05-1.12; p < 0.001). Receiver operating characteristic analysis showed that baseline urinary L-FABP level exhibited 94.2% sensitivity and 87.0% specificity at a cutoff value of 12.5 μg/g Cr.Urinary L-FABP level is useful for predicting the onset of AKI in patients with ADHF. The results of our study could help clinicians diagnose AKI in ADHF patients earlier, leading to possible improvements in the treatment of this group of patients.
Pharmacologic beta-blockade is a well-established therapy for reducing adverse effects from sympathetic overactivity in cardiovascular diseases, such as heart failure. Despite decades of research efforts, in vivo cardiac functional studies utilizing genetic animal models remain scant. We generated a mouse model of cardiomyocyte-specific deletion of beta-1 adrenergic receptor (ADRB1) , the primary subtype expressed in cardiac myocytes, and demonstrated the role for ADRB1 in the maintenance of cardiac function at baseline and during exposure to increase in cardiac afterload by transient aortic occlusion and increasing heart rates (HRs) via atrial pacing. cKO hearts showed mildly depressed baseline left ventricular (LV) function, including slower HR, decreased contractility (dP/dtmax/IP) and prolonged relaxation (Tau) at baseline in both sexes. Exposure to increased LV afterload depressed LV function in either genotype similarly; however, the functional recovery following the removal of the afterload was severely impaired in cKO hearts, while cardiac function was immediately normalized in WT hearts. When HR was altered from 400 to 700bpm, cKO hearts were deficient in HR-dependent improvement of cardiac contractility and relaxation, known as positive force frequency relationship, that was evident in WT hearts. Enhanced phosphorylation of phospholamban by the HR increase was markedly blunted in cKO myocardium vs wild types, while CaMKII phosphorylation was comparable between the genotypes, suggesting the critical involvement of PKA. These results provide the first experimental evidence for the role of ADRB1 in cardiomyocytes for maintaining cardiac function at baseline and during acute stress, providing clinical perspective relating to the management of patients on beta-blockers.
