Endotrophin as a Biomarker for Severe Acute Kidney Injury and Major Adverse Kidney Events

Abstract

Key Points:

1. Endotrophin (ETP), a circulating marker of fibroinflammation, is elevated in critically ill patients with AKI.

2. ETP is independently associated with major adverse kidney events at hospital discharge.

3. Sustained elevations of ETP at 5–7 days are associated with major adverse kidney events.

Background: The search for novel biomarkers in AKI continues, both for being able to predict adverse events in AKI but also for confirming pathogenic pathways as potential therapeutic targets. Endotrophin (ETP) is an emerging biomarker in a number of fibroinflammatory diseases. We sought to test the association of ETP with the development of a major adverse kidney event (MAKE) in critically ill adult patients.

Methods: Single-center prospective study of critically ill adult patients with stage 2–3 AKI and patients without AKI. Serum ETP was measured early in the first 3 days of critical care admission, 5–7 days later, and in some patients, 4–6 weeks later. The primary outcome was MAKE assessed at hospital discharge, a composite of mortality, RRT at discharge, and eGFR reduction of ≥25% from baseline.

Results: Among 121 patients evaluated in this study, serum ETP was significantly higher in patients with AKI versus those without (P < 0.05). In multivariable logistic regression analysis, higher tertiles of ETP were significantly associated with MAKE at discharge, controlled for relevant covariates. Furthermore, sustained elevations in ETP 5–7 days later, as opposed to reductions toward normal, were also associated with MAKE. In patients seen in the clinic 4–6 weeks post-AKI, ETP remained elevated. In the acute period, ETP levels correlated most with TNF-α and neutrophil gelatinase-associated lipocalin.

Conclusions: Higher levels of serum ETP early in the intensive care unit admission, as well as sustained elevations of ETP within a 5-day to 7-day period, are associated with MAKE at hospital discharge. ETP is a potential biomarker of AKI-related outcomes and a promising therapeutic target to minimize sequelae of AKI.

Graphical abstract

Figure 1

ETP levels between AKI and no AKI groups at three time points: (1) early in ICU, (2) 5–7 days later, and (3) 4–6 weeks later. ETP, endotrophin; ICU, intensive care unit.

Figure 2

The figure depicts the correlations between these biomarkers. Heat map of ETP levels versus other cytokines included in the biobank at time point 1 (A) and 5–7 days later (B).