Kidney Week

Abstract: TH-PO101

Cell Cycle Biomarkers and Soluble Urokinase-Type Plasminogen Activator Receptor for the Prediction of Septic AKI Courses Requiring Renal Replacement Therapy: An Explorative Study

Session Information

• AKI: Biomarkers, Drugs, Onco-Nephrology
  November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• Nusshag, Christian, Heidelberg University Hospital, Heidelberg, Germany

Christian Nusshag,

• Rupp, Christoph, Heidelberg University Hospital, Heidelberg, Germany

Christoph Rupp,

• Speer, Claudius, Heidelberg University Hospital, Heidelberg, Germany

Claudius Speer,

• Kälble, Florian, Heidelberg University Hospital, Heidelberg, Germany

Florian Kälble,

• Krautkrämer, Ellen, Heidelberg University Hospital, Heidelberg, Germany

Ellen Krautkrämer,

• Zeier, Martin G., Heidelberg University Hospital, Heidelberg, Germany

Martin G. Zeier,

• Reiser, Jochen, Rush University Medical Center, Chicago, Illinois, United States

Jochen Reiser,

• Weigand, Markus A., Heidelberg University Hospital, Heidelberg, Germany

Markus A. Weigand,

• Uhle, Florian, Heidelberg University Hospital, Heidelberg, Germany

Florian Uhle,

• Merle, Uta, University Hospital Heidelberg, Heidelberg, BW, Germany

Uta Merle,

• Morath, Christian, University of Heidelberg, Heidelberg, Germany

Christian Morath,

• Brenner, Thorsten, Heidelberg University Hospital, Heidelberg, Germany

Thorsten Brenner,

Background

Sepsis-induced acute kidney injury (AKI) is the dominant AKI etiology in critically ill patients and is often associated with the need for renal replacement therapy (RRT). The timinig of RRT is an ongoing controversy. A major issue that persists is the early differentiation of patients with progressive AKI and need for RRT from those with autonomous renal recovery. We hypothesized, that the product of the two cell cycle arrest and tubular injury biomarkers tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2]*[IGFBP7]), and the soluble urokinase-type plasminogen activator receptor (suPAR) are of diagnostic value for the prediction of septic AKI courses requiring RRT.

Methods

100 critically ill patients were enrolled prospectively after the fulfillment of Sepsis-3 criteria. Urinary [TIMP-2]*[IGFBP7] levels over time and serum suPAR levels once at inclusion were measured. The primary clinical endpoint was the occurrence of need for RRT within 7 days. Area under the receiver-operating characteristic curves (AUC-ROC), deLong’s tests and logistic regression models were calculated.

Results

Nineteen patients developed need for RRT. Diagnostic performance of urinary [TIMP-2]*[IGFBP7] improved significantly over time with the highest AUC of 0.89 (95%CI 0.80-0.98) at 24h after study inclusion. SuPAR levels at inclusion showed an AUC of 0.83 (0.75-0.92). The best discrimination ability for the primary outcome measure was achieved for [TIMP-2]*[IGFBP7]24h by applying a cut-off value of ≥0.6 (ng/ml²)/1000 (sensitivity 90.9, specificity 67.1). SuPAR at inclusion performed best by using a cut-off value of ≥8.53 ng/mL (sensitivity 84.2, specificity 82.7). The combination of newly tested biomarkers with cystatin C (CysC) resulted in a significantly improved diagnostic accuracy. CysC in combination with [TIMP-2]*[IGFBP7]24h outperformed all present standard renal parameters (AUC 0.93 [0.86-1.00]).

Conclusion

[TIMP-2]*[IGFBP7] levels after the initiation of therapeutic measures and suPAR levels at baseline are promising biomarker candidates for the risk stratification of septic AKI patients with the need for RRT.