P0565EVALUATION OF THE WNT SIGNALING PATHWAY AS A PROGNOSTIC MARKER IN PATIENTS WITH UROSEPSIS
Authors: Oh Dong-Jin , Shin Jungho 
Published: June 2020

Background and Aims

Sepsis is a serious condition characterized by a dysregulated inflammatory response to infection, leading to life threatening organ dysfunction. Acute kidney injury (AKI) is one of sepsis-induced organ dysfunction and results in extremely high morbidity and mortality. Emerging evidence demonstrated the relationship between the Wnt signaling pathway and inflammation. In vitro and in vivo studies reported that inhibition of canonical Wnt/β-catenin signaling attenuates the sepsis-induced organ injury and systemic inflammation. On the other hand, Wnt5a, a typical glycoprotein of the non-canonical pathway, may have proinflammatory functions. Studies showed that Wnt5a levels are elevated in patients with sepsis. Despite potentials, there is a paucity of studies evaluating these pathways and correlating it with clinical data, particularly in patients with sepsis. Therefore, this prospective observational study investigated the association between the Wnt pathway and clinical outcomes in patients with urosepsis.

Method

Adult patients (&gt;18 years of age) with urinary tract infection admitted to the intensive care unit of the Myongji Hospital were screened for sepsis according to the 2012 Surviving Sepsis Campaign Guidelines. Thereafter, 38 subjects who were diagnosed with urosepsis were included in the study. Twenty healthy volunteers (10 males and 10 females, aged 55–64 years) were recruited into the control group. In patient serum creatinine levels at day 0, day 5, and at discharge day were obtained for accessing renal recovery. Wnt3a and Wnt5a levels were measured at admission. Levels of Wnt3a and Wnt5a proteins were evaluated using the enzyme-linked immunosorbent assay (ABclonal Biotechnology, Woburn, MA, USA). The primary composite outcome was the incidence of Major Adverse Kidney Events (MAKE), which was defined as new renal replacement therapy, stage 3 AKI by the guideline of the Kidney Disease Improving Global Outcomes, or death. Thereafter, the levels of Wnt3a and Wnt5a were evaluated to predict the primary composite outcome.

Results

1) Both Wnt3a and Wnt5a levels were significantly increased in the urosepsis group (P = 0.001 and P &lt; 0.001 respectively) compared to normal individuals. 2) Out of 38 included patients with urosepsis, MAKE occurred in 13 (34.2%) subjects. The patients were divided into two groups, with MAKE (13 patients, 34.2%) and without MAKE (25 patients, 65.8%). No significant difference in the levels of Wnt3a was observed between the two groups (P = 0.927); however, the levels of Wnt5a were higher in the patients with MAKE than in those without MAKE (P = 0.015). 3) Results showed that Wnt5a levels could be a predictor for the occurrence of MAKE, while Wnt3a levels are not (P = 0.927). The area under the curve of Wnt5a was 0.74 (95% confidence interval 0.57– 0.92; P = 0.016). 4) The levels of serum creatinine at discharge were higher in the Wnt5a high group than in the Wnt5a low group (P = 0.030) although the levels on day 0 and day 5 were similar (P = 0.201 and 0.233 respectively).

Conclusion

This study confirmed the elevated levels of Wnt3a and Wnt5a in patients with urosepsis. It furthermore identified that the elevated levels of Wnt5a could predict a higher incidence of MAKE and non recovery of renal function in the patients; however, Wnt3a levels are not associated with MAKE and renal recovery. Accordingly, we suggest that Wnt5a levels can be used as a prognostic marker in patients with sepsis. Further studies with a larger number of subjects are required to confirm the utility of Wnt5a as a biomarker in various diseases including sepsis. This study also suggests the potentials of the Wnt signaling pathway as novel therapeutic targets in sepsis.