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

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.