Project title
Renal ultrasound elastometry and urine metabolomics: precise diagnostic biomarkers for acute kidney injury in cirrhosis
Acronyme and code
RULE-IN AKI (PN-IV-P2-2.1-TE-2023-0168)
Funding
UEFISCDI – contract nr. 74TE/03/01/2025
Value
100.000,00 EUR
Duration
24 months (03/01/2025 – 31/12/2026)
Team members
- Dana Crișan, MD, post-doctoral researcher – Project leader
- Horia Ștefănescu, post-doctoral researcher
- Petra Fischer, post-doctoral researcher
- Rareș Crăciun, PhD student
- Tăluță-Băieș Cornelia, PhD student
- Cosma Tudor, PhD student
Objectives
Acute kidney injury (AKI) is a common complication in patients with advanced liver disease, and its subtypes are classified according to the pathophysiological mechanism: pre-renal, renal (acute tubular necrosis and hepatorenal syndrome), and post-renal (obstructive). In approximately 68% of cases, the impairment is pre-renal, with a favorable response to volume repletion using crystalloids and Albumin.
Hepatorenal syndrome (HRS) is one of the most severe complication of decompensated liver cirrhosis due to its high mortality and poor prognosis. Its pathophysiological mechanism involves a combination of renal vasoconstriction and systemic inflammation. In recent years, the definition of hepatorenal syndrome has been revised, but serum creatinine level has remained the main diagnostic criterion for HRS despite multiple limitations. For this reason, new serum and urinary biomarkers have been extensively studied, with inconsistent results. Imaging methods such as renal elastography, contrast-enhanced ultrasound, and renal Doppler have been investigated to a lesser extent, all in an attempt to validate new early diagnostic criteria for HRS as well as to differentiate this condition from other subtypes of kidney dysfunction.
We hypothesize that HRS-specific hemodynamic changes can be captured by the analysis of renal stiffness (RSM) using shear-wave elastography (SWE) and dynamic contrast-enhanced ultrasound (D-CEUS) with time-intensity curve (TIC) analysis. Moreover, specific urinary biomarkers derived from the shift towards an anaerobic metabolism should be detected by metabolomics. Thus, the RULE-IN AKI project proposes an approach that consists of two human clinical studies (training and validation), aiming to study the role of RSM, renal D-CEUS, and urinary biomarkers in the diagnosis of HRS, the discrimination from acute tubular necrosis (ATN) and prediction of treatment response.
Therefore, our main objectives are:
- Assessment of the diagnostic role of ultrasound parameters (elastography, dynamic contrast-enhanced ultrasound (D-CEUS) with time-intensity curve (TIC) analysis, renal Doppler through measurement of the resistive index (RI) of the interlobular renal arteries) in differentiating between ATN and HRS in cirrhotic patients.
- Evaluation of both serum and urinary biomarkers (Kim-1, Fatty Acid–Binding Proteins (FABPs), NGAL Neutrophil Gelatinase–Associated Lipocalin (NGAL), Interleukin-18 (IL-18)) for the purpose of establishing cut-off values to differentiate the various subgroups of renal dysfunction in patients with decompensated advanced liver disease.
- Urinary metabolomic analysis.
- Evaluation of therapeutic response to vasopressor administration in the group that meets the criteria for hepatorenal syndrome.
Activities and Milestones
A1 – Patient’s evaluation and enrolment.
A2 – Assessment of renal ultrasound in different group of patients (healthy control group / compensated cirrhosis control group / decompensated cirrhosis control group / decompensated cirrhosis with acute kidney dysfunction group).
A3 – Assessment of urinary and serum biomarkers in the groups of patients above mentioned. Assessment of urinary metabolomics.
A4 – Data integration and interpretation. Dissemination of the results.
A5 – Project management.
