Prediction models combining zonulin, LPS, and LBP predict acute kidney injury and hepatorenal syndrome–acute kidney injury in cirrhotic patients

Abstract

Abstract The development of acute kidney injury (AKI) and hepatorenal syndrome-acute kidney injury (HRS-AKI) in cirrhosis has been associated with intestinal barrier dysfunction and gut-kidney crosstalk. We use the related markers such as zonulin, lipopolysaccharides (LPS), and lipopolysaccharide-binding protein (LBP) to predict AKI and HRS-AKI in cirrhotic patients and evaluate their in vitro effects on intestinal (Caco-2) cells and renal tubular (HK-2) cells. From 2013 to 2020, we enrolled 70 cirrhotic patients and developed prediction models for AKI and HRS-AKI over a six-month period. There were 13 (18.6%) and 8 (11.4%) cirrhotic patients who developed AKI and HRS-AKI. The prediction models incorporated zonulin, LPS, LBP, C-reactive protein, age, and history of hepatitis B for AKI, and zonulin, LPS, LBP, total bilirubin, and Child-Pugh score for HRS-AKI. The area under curve (AUC) for the prediction of AKI and HRS-AKI was 0.94 and 0.95, respectively. Furthermore, the conditioned medium of LPS + hrLBP pre-treated Caco-2 cells induced apoptosis, necrosis, and zonulin release in HK-2 cells, demonstrating the communication between them. This study found that zonulin, LPS, and LBP are potential practical markers for predicting AKI and HRS-AKI in cirrhotic patients, which may serve as potential targets for renal outcomes in cirrhotic patients.