Plasma thrombomodulin levels are associated with acute kidney injury in patients with acute heart failure

Abstract

Cardiorenal syndrome type I (CRS I) is defined as the development of acute kidney injury (AKI) following acute decompensated heart failure (ADHF). The clinical significance of endothelial markers in ADHF-associated AKI has yet to be clarified. This study therefore investigated the biological processes linking ADHF and AKI with the aim of determining whether the plasma markers of endothelial injury and activation are associated with AKI in patients with ADHF. The study prospectively recruited 125 consecutive patients admitted to a coronary critical unit due to ADHF. Patients with and without AKI were compared in terms of soluble thrombomodulin (sTM), angiopoietin (Ang)-1 and −2 plasma levels as well as baseline characteristics. Among the study population, 14 (11.2%) patients developed CRS within 7 days after admission. The hemoglobin levels (median [IQR]11.3[10.8–12.6] vs. 13.5 [12.2–15.0] g/dL, p = 0.003) and baseline eGFR (66.5[35.7–87.9] vs. 78.5 [64.9–107.5] mL/minute/1.73m2, p = 0.044) of patients with CRS were lower than those of patients without CRS. Patients with CRS also presented elevated plasma levels of BNP (1317.5 [222.6–3375.5] vs. 258.2 [63.2–925.8] pg/mL, p = 0.008), Ang-2 (3993.0 [1561.3–15722.7] vs. 1805.9 [1196.9–3302.3] pg/mL, p = 0.006), and sTM (6665.7 [4707.1–11947.3] vs. 4132.2 [3338.0–5531.8] ng/mL, p < 0.001), compared to patients without CRS. Multivariate logistic regression analysis based on forward stepwise method identified that log sTM was the only independent risk factor for AKI (OR, 13.83; 3.02–63.28, p = 0.001). Furthermore, higher sTM levels were associated with AKI in patients with ADHF. These findings suggest a novel approach to dealing with kidney injury in the context of ADHF, involving the use of baseline biomarker profiles to identify individuals at risk of developing AKI. KEY MESSAGES The clinical significance of endothelial markers in acute decompensated heart failure (ADHF)-associated acute kidney injury (AKI) has not previously been clarified. This study revealed that markers of endothelial injury (i.e. plasma soluble thrombomodulin (sTM) levels) were higher in ADHF patients with AKI than in those without AKI. Multivariate analysis identified sTM level > cutoff value of 4,855.2 pg/mL as an independent factor associated with the development of AKI. sTM could potentially be used as a biomarker to predict the development of AKI in patients with heart failure. These findings suggest a novel approach to dealing with kidney injury in the context of ADHF, involving the use of baseline biomarker profiles to identify individuals at risk of developing AKI.