Reducing incidence of postoperative acute kidney injury in trauma and orthopaedics patients: a quality improvement project.

BACKGROUND: Acute kidney injury (AKI) is a common postoperative complication which increases morbidity and mortality. This quality improvement project aimed to implement measures targeting known risk factors to decrease the incidence of postoperative AKI in trauma and orthopaedics (T&O) patients. METHODS: Data were collected across three six-month to 7-month cycles between 2017 and 2020, analysing all elective and emergency T&O operated patients within a single NHS Trust (n=714, 1008 and 928, respectively). Patients who developed a postoperative AKI were identified using biochemical criteria and data were collected on known AKI risk factors, including use of nephrotoxic medications, and patient outcomes. In the final cycle, the same variables were collected for patients without AKI. Between cycles, measures implemented included: preoperative and postoperative medication reconciliation aiming to stop nephrotoxic medications, orthogeriatrician review of high-risk patients and junior doctor teaching on fluid therapy. Statistical analysis was undertaken to determine the incidence of postoperative AKI across cycles, prevalence of risk factors and impact on length of hospital stay and postoperative mortality. RESULTS: There was a statistically significant decrease in postoperative AKI incidence from 4.27% (43 of 1008 patients) in cycle 2 to 2.05% (19 of 928) in cycle 3 (p=0.006), with a notable decrease in use of nephrotoxic medications. Significant predictors for the development of postoperative AKI included use of diuretics and receiving multiple nephrotoxic drug classes. Development of postoperative AKI significantly increased length of hospital stay by 7.11 days on average (95% CI: 4.84 to 9.38 days, p<0.001) and risk of 1-year postoperative mortality (OR 3.22, 95% CI: 1.03 to 10.55, p=0.046). CONCLUSION: This project demonstrates that a multifaceted approach targeting modifiable risk factors can reduce incidence of postoperative AKI in T&O patients, which may lead to reduced length of hospital stay and postoperative mortality.

Platelet adhesion to podoplanin under flow is mediated by the receptor CLEC-2 and stabilised by Src/Syk-dependent platelet signalling.

Platelet-specific deletion of CLEC-2, which signals through Src and Syk kinases, or global deletion of its ligand podoplanin results in blood-filled lymphatics during mouse development. Platelet-specific Syk deficiency phenocopies this defect, indicating that platelet activation is required for lymphatic development. In the present study, we investigated whether CLEC-2-podoplanin interactions could support platelet arrest from blood flow and whether platelet signalling is required for stable platelet adhesion to lymphatic endothelial cells (LECs) and recombinant podoplanin under flow. Perfusion of human or mouse blood over human LEC monolayers led to platelet adhesion and aggregation. Following αIIbß3 blockade, individual platelets still adhered. Platelet binding occurred at venous but not arterial shear rates. There was no adhesion using CLEC-2-deficient blood or to vascular endothelial cells (which lack podoplanin). Perfusion of human blood over human Fc-podoplanin (hFcPDPN) in the presence of monoclonal antibody IV.3 to block FcγRIIA receptors led to platelet arrest at similar shear rates to those used on LECs. Src and Syk inhibitors significantly reduced global adhesion of human or mouse platelets to LECs and hFcPDPN. A similar result was seen using Syk-deficient mouse platelets. Reduced platelet adhesion was due to a decrease in the stability of binding. In conclusion, our data reveal that CLEC-2 is an adhesive receptor that supports platelet arrest to podoplanin under venous shear. Src/Syk-dependent signalling stabilises platelet adhesion to podoplanin, providing a possible molecular mechanism contributing to the lymphatic defects of Syk-deficient mice.