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Kidney Week

Abstract: PO0211

suPAR Determines Outcomes in Septic AKI

Session Information

  • AKI Mechanisms - 2
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Nusshag, Christian, Rush University Medical Center, Chicago, United States
  • Wei, David Changli, Rush University Medical Center, Chicago, Illinois, United States
  • Szudarek, Roman, Heidelberg University Hospital, Heidelberg, Germany
  • Kälble, Florian, Heidelberg University Hospital, Heidelberg, Germany
  • Speer, Claudius, Heidelberg University Hospital, Heidelberg, Germany
  • Uhle, Florian, Heidelberg University Hospital, Heidelberg, Germany
  • Eugen-Olsen, Jesper, Copenhagen university hospital Hvidovr, Hvidovre, Denmark
  • Krarup, Thomas, ViroGates A/S, Birkerod, Hovedstaden, Denmark
  • Weigand, Markus A., Heidelberg University Hospital, Heidelberg, Germany
  • Zeier, Martin G., Heidelberg University Hospital, Heidelberg, Germany
  • Morath, Christian, Heidelberg University Hospital, Heidelberg, Germany
  • Brenner, Thorsten, University Hospital Essen, Essen, Germany
  • Reiser, Jochen, Rush University Medical Center, Chicago, Illinois, United States
Background

Sepsis is the main contributor to the development of acute kidney injury (AKI) in critically ill patients. Plasma soluble urokinase plasminogen activator receptor (suPAR) is a criculating risk factor for AKI and a prognostic marker for the need of renal replacement therapy (RRT). We analyzed the pathophysiological role and kinetic properties of suPAR in septic AKI in critically ill patients and in a murine model of septic AKI.

Methods

200 critically ill patients were enrolled prospectively after meeting Sepsis-3 criteria. Serum suPAR levels were measured at 0, 12, 24, 48, 72, 96, 120 and 168-hour after enrollment and the need for RRT within 7 days was assessed as the primary outcome measure. Polybacterial sepsis was induced by cecal slurry injection in three mouse strains, respectively wild type (WT, N=9), uPAR-knockout (KO, N=13), and suPAR transgenic overexpression (OE, N=11).

Results

No or mild AKI occurred in 62 patients (31.0%), moderate or severe AKI without the need for RRT in 102 patients (51.0%), criteria for RRT were met in 36 patients (18.0%) and 7 patients (3.5%) died within the 7-day period. Compared to all other maximum AKI stages and AKI disease courses within 7 days, patients requiring RRT showed significantly higher suPAR levels at all time-points. Patients with suPAR levels ≥ 12.7 ng/mL (highest quartile) had an adjusted odds ratio of 5.22 (95% confidence interval [CI], 2.16-12.65) for the need for RRT; and 4.44 (95% CI, 1.98-9.97) for RRT or death within 7 days compared to patients with levels < 12.7 ng/mL. Compared to KO mice, WT and OE mice showed a significantly greater impairment of renal function and structure 24 hours after induction of sepsis. Kaplan-Meier analysis revealed a survival benefit of KO mice over OE mice within 24h (84.6% vs. 45.5%, p=0.041).

Conclusion

SuPAR distinguishes between divergent AKI stages/courses and the need for RRT at any time within 7 days after sepsis diagnosis. Our experimental data suggest that suPAR is a pathophysiological driver of septic AKI and may serve as a target for future interventional strategies.