Endothelial glycocalyx participates in the maintenance of vascular integrity, and its perturbations cause capillary leakage, loss of vascular responsiveness, and enhanced adhesion of leukocytes and platelets. We hypothesized that marked shedding of the glycocalyx core protein, syndecan-1, occurs in end-stage liver disease (ESLD) and that it increases during orthotopic liver transplantation (OLT). We further evaluated the effects of general anesthesia on glycocalyx shedding and its association with acute kidney injury (AKI) after OLT. Thirty consecutive liver transplant recipients were enrolled in this prospective study. Ten healthy volunteers served as a control. Acute kidney injury was defined by Acute Kidney Injury Network criteria. Plasma syndecan-1 was significantly higher in ESLD patients than in healthy volunteers (74.3 ± 59.9 vs 10.7 ± 9.4 ng/mL), and it further increased significantly after reperfusion (74.3 ± 59.9 vs 312.6 ± 114.8 ng/mL). The type of general anesthesia had no significant effect on syndecan-1. Syndecan-1 was significantly higher during the entire study in patients with posttransplant AKI stage 2 or 3 compared to patients with AKI stage 0 or 1. The area under the curve of the receiver operating characteristics curve of syndecane-1 to predict AKI stage 2 or 3 within 48 hours after reperfusion was 0.76 (95% confidence interval, 0.57-0.89, P = 0.005). Patients with ESLD suffer from glycocalyx alterations, and ischemia-reperfusion injury during OLT further exacerbates its damage. Despite a higher incidence of AKI in patients with elevated syndecan-1, it is not helpful to predict de novo AKI. Volatile anesthetics did not attenuate glycocalyx shedding in human OLT.

Objective: Regional citrate anticoagulation has emerged as a promising method in critically ill patients at high risk of bleeding. However, in patients with liver failure, citrate accumulation may lead to acid-base and electrolyte imbalances, notably of calcium. The aim of this study was to evaluate the feasibility and safety of regional citrate anticoagulation during liver support using a molecular adsorbent recirculating system as well as its effects on electrolyte and acid-base balance in patients with liver failure. Design: Prospective observational study. Setting: University hospital. Patients: Twenty critically ill patients supported by molecular adsorbent recirculating system resulting from liver failure between January 2007 and May 2009. Measurements and Main Results: The median duration of molecular adsorbent recirculating system treatment was 20 hrs (interquartile range, 18−22 hrs). Two of 77 molecular adsorbent recirculating system treatments (2%) were prematurely discontinued as a result of filter clotting and bleeding, respectively. The median citrate infusion rate, necessary to maintain the postfilter ionized calcium between 0.2 and 0.4 mmol/L, was 3.1 mmol/L (interquartile range, 2.3–4 mmol/L) blood flow. The median calcium chloride substitution rate was 0.9 mmol/L (0.3–1.7 mmol/L) dialysate. Total serum calcium remained stable during molecular adsorbent recirculating system treatments. There was a statistically significant increase of the ratio of total calcium to systemic ionized calcium (2.04 ± 0.32 mmol/L to 2.17 ± 0.35; p = .01), which reflected citrate accumulation resulting from liver failure. Under close monitoring, no clinically relevant electrolytes or acid-base disorders were observed. Conclusions: Our results suggest that regional citrate anticoagulation is a safe and feasible method to maintain adequate circuit lifespan without increasing the risk of hemorrhagic complications while maintaining a normal acid-base as well as electrolyte balance in patients with liver failure supported by molecular adsorbent recirculating system.

Background.: Destruction of the endothelial glycocalyx has been observed within lung and kidney grafts during ischemic organ preservation. We aimed to quantify glycocalyx damage within human liver grafts after organ preservation and correlate the results with graft injury and postoperative graft function in patients undergoing orthotopic liver transplantation (OLT). Methods.: Syndecan-1 (Sdc-1) was measured as indicator of glycocalyx degradation in effluents of 38 liver grafts and serum of patients undergoing OLT. Effluent Sdc-1 concentrations were correlated with hepatic injury markers from the effluent. Furthermore, we assessed the association of Sdc-1 with early allograft dysfunction (EAD), 1-year graft survival, and 1-year patient survival. Results.: Effluent Sdc-1 concentrations correlated with effluent concentrations of hepatocellular injury markers, including alkaline phosphatase (R = 0.543, P = 0.003), aspartate aminotransferase (R = 0.420, P = 0.029), and lactate (R = 0.574, P = 0.002). Sdc-1 effluent concentrations were greater in patients who developed EAD compared with those without EAD (4720 [4374–5133] vs 3838 [3202–4240] ng/mL, P = 0.015). Furthermore, receiver operating characteristics analyses revealed that effluent Sdc-1 concentrations (AUC = 0.82, P = 0.017) and serum Sdc-1 concentrations (AUC = 0.84, P = 0.006) were associated with the development of EAD. These results were confirmed by regression analyses. No association was found between Sdc-1 and 1-year graft survival or 1-year patient survival. Conclusions.: Our data suggest that the glycocalyx is damaged within human liver grafts during preservation and the extent of glycocalyx damage correlates with the severity of hepatocellular injury. Recipients of livers grafts with greater glycocalyx damage might be at higher risk for development of EAD after OLT.

Summary: Anaemia is common in patients with end‐stage liver disease. Pre‐operative anaemia is associated with greater mortality after major surgery. We analysed the association of pre‐operative anaemia (World Health Organization classification) with survival and complications after orthotopic liver transplantation using Cox and logistic regression models. We included patients undergoing their first orthotopic liver transplantation between 2004 and 2016. Out of 599 included patients, 455 (76%) were anaemic before transplantation. Pre‐operative anaemia was not associated with the survival of 485/599 (81%) patients to 1 year after liver transplantation, OR (95% CI ) 1.04 (0.64–1.68), p = 0.88. Pre‐operative anaemia was associated with higher rates of intra‐operative blood transfusions and acute postoperative kidney injury on multivariable analysis, OR (95% CI ) 1.70 (0.82–2.59) and 1.72 (1.11–2.67), respectively, p < 0.001 for both. Postoperative renal replacement therapy was associated with pre‐operative anaemia on univariate analysis, OR (95% CI ) 1.87 (1.11–3.15), p = 0.018.

Several biomarkers have been suggested as early predictors of acute kidney injury (AKI) after orthotopic liver transplantation (OLT). Neutrophil gelatinase-associated lipocalin-2 (NGAL) appears to be a promising predictor of AKI after OLT, but the clinical benefit remains to be proven. Recently, systemic macrophage migration inhibitory factor (MIF) has been proposed as early indicator for requirement of renal replacement therapy after OLT. The aim of this prospective, observational pilot study was to compare the predictive values of serum and urinary MIF for severe AKI after OLT to those of serum and urinary NGAL. Concentrations of MIF and NGAL were measured in serum and urine samples collected from patients undergoing OLT. Acute kidney injury was classified according to the KDIGO criteria, with stages 2 and 3 summarized as severe AKI. Areas under the receiver operating curves (AUC) were calculated to assess predictive values of MIF and NGAL for the development of severe AKI. Forty-five patients (mean age 55±8 years) were included. Nineteen patients (38%) developed severe AKI within 48 hours after reperfusion. At the end of OLT, serum MIF was predictive of severe AKI (AUC 0.73; 95% confidence intervals, CI 0.55–0.90; P = 0.03), whereas urinary MIF, serum NGAL, and urinary NGAL were not. On the first postoperative day, serum MIF (AUC 0.78; CI 0.62–0.93; P = 0.006), urinary MIF (AUC 0.71; CI 0.53–0.88; P = 0.03), and urinary NGAL (AUC 0.79; CI 0.64–0.93; P = 0.02) were predictive for severe AKI, while serum NGAL was not. In the setting of OLT, MIF and NGAL had similar predictive values for the development of severe AKI.