Aims: Increases in the systemic vasodilator adrenomedullin and the renal vasoconstrictors thromboxane A2 in cirrhotic patients are pathogenic factors for the development of functional acute kidney injury (AKI), including pre-renal azotemia (PRA) and hepatorenal syndrome (HRS), which is associated with high mortality. This study aims to find biomarkers that can diagnose HRS at an early stage, to enable treatment as soon as possible.
Methods: Acute decompensated cirrhotic patients who had been admitted to hospital were enrolled in this prospective cohort study. Blood and urinary samples were collected immediately after admission. In addition to initially categorizing AKI cases into PRA, acute tubular necrosis (ATN), and HRS groups, their final diagnosis was adjudicated by a nephrologist and a hepatologist who checked the corrected and misclassification rates for significant biomarkers.
Results: The cut-off values for serum adrenomedullin and urinary thromboxane B2 (TXB2 ), when used as predictors for functional AKI (adrenomedullin >283 pg/mL, urinary TXB2 >978 [pg/mg urinary creatinine]), for HRS (adrenomedullin >428, urinary TXB2 >1604), and for good terlipressin plus albumin treatment responders (adrenomedullin >490, urinary TXB2 >1863), were observed. Patients with HRS who could be treated, due to high mortality, had significantly higher serum adrenomedullin and urinary TXB2 levels compared to HRS patients receiving standard treatment. In addition to predicting 60-day mortality, a combination of these two markers further increased diagnostic accuracy for HRS among functional AKI.
Conclusions: Prompt diagnosis of HRS by differentiating it from PRA and ATN can be achieved by using serum adrenomedullin and urinary TXB2 in acute decompensated cirrhotic patients. In combination with severe clinical courses, these two markers are useful to select HRS patients who cannot be treated.
Keywords: acute kidney injury; acute tubular necrosis; biomarkers; hepatorenal syndrome.
© 2017 The Japan Society of Hepatology.