Serum adrenomedullin and urinary thromboxane B2 help early categorizing of acute kidney injury in decompensated cirrhotic patients: A prospective cohort study

Aims Increases in the systemic vasodilator adrenomedullin and the renal vasoconstrictors thromboxane A2 (TXA2) in cirrhotic patients are pathogenic factors for the development of functional acute-kidney-injury, including pre-renal azotemia (PRA) and hepatorenal syndrome (HRS), which is associated with high mortality. This study aims to find biomarkers which can diagnose HRS in early stage for treating it 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 acute-kidney-injury 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 cutoff values for serum adrenomedullin and urinary TXB2, when used as predictors for functional acute kidney injury {[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. HRS patients who can't 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 acute-kidney-injury. Conclusions Prompt diagnosis of HRS by differentiating it from PRA and ATN can be achieved by using serum adrenomedullin and urinary TXB2 in acute de-compensated cirrhotic patients. In combination with severe clinical courses, these two markers are useful to select HRS patients who can't be treated.