Urinary actin, as a potential marker of sepsis-related acute kidney injury: A pilot study

Dániel Ragán, Péter Kustán, Zoltán Horváth-Szalai, Balázs Szirmay, Beáta Bugyi, Andrea Ludány, Attila Miseta, Bálint Nagy, Diána Mühl, Dániel Ragán, Péter Kustán, Zoltán Horváth-Szalai, Balázs Szirmay, Beáta Bugyi, Andrea Ludány, Attila Miseta, Bálint Nagy, Diána Mühl

Abstract

Introduction: A major complication of sepsis is the development of acute kidney injury (AKI). Recently, it was shown that intracellular actin released from damaged tissues appears in the urine of patients with multiple organ dysfunction syndrome. Our aims were to measure urinary actin (u-actin) concentrations of septic and control patients and to test if u-actin levels could predict AKI and mortality.

Methods: Blood and urine samples were collected from septic and sepsis-related AKI patients at three time points (T1-3): T1: within 24 hours after admission; T2: second day morning; T3: third day morning of follow-up. Patients with malignancies needing palliative care, end-stage renal disease or kidney transplantation were excluded. Serum and u-actin levels were determined by quantitative Western blot. Patients were categorized by the Sepsis-3 and KDIGO AKI classifications.

Results: In our study, 17 septic, 43 sepsis-induced AKI and 24 control patients were enrolled. U-actin levels were higher in septic patients compared with controls during follow-up (p<0.001). At T1, the septic and sepsis-related AKI groups also showed differences (p<0.001), yet this increase was not statistically significant at T2 and T3. We also detected significantly elevated u-actin concentrations in AKI-2 and AKI-3 septic patients compared with AKI-1 septic patients (p<0.05) at T1 and T3, along with a significant increase in AKI-2 septic patients compared with AKI-1 septic patients at T2 (p<0.01). This tendency remained the same when referring u-actin to urine creatinine. Parameters of first-day septic patient samples could discriminate AKI from non-AKI state (AUC ROC, p<0.001): u-actin: 0.876; se-creatinine: 0.875. Derived cut-off value for u-actin was 2.63 μg/L (sensitivity: 86.0%, specificity: 82.4%).

Conclusion: U-actin may be a complementary diagnostic biomarker to se-creatinine in sepsis-related AKI while higher u-actin levels also seem to reflect the severity of AKI. Further investigations may elucidate the importance of u-actin release in sepsis-related AKI.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Urinary actin in sepsis.
Fig 1. Urinary actin in sepsis.
U-actin levels of control and septic patients (A) along with sepsis and sepsis-related AKI patients (B) during follow-up. n: sample count. **p

Fig 2. Urinary actin in sepsis-related AKI.

Fig 2. Urinary actin in sepsis-related AKI.

U-actin (A) and u-actin/u-creatinine (B) levels of the…

Fig 2. Urinary actin in sepsis-related AKI.
U-actin (A) and u-actin/u-creatinine (B) levels of the individual sepsis-related AKI stages during follow-up. n: sample count. *p

Fig 3. Survival and predictive power of…

Fig 3. Survival and predictive power of urinary actin.

U-actin levels in survivor and non-survivor…

Fig 3. Survival and predictive power of urinary actin.
U-actin levels in survivor and non-survivor septic patients based on 30-day mortality during follow-up (A). Receiver operating characteristic (ROC) curves of admission laboratory parameters for distinguishing sepsis from sepsis-related AKI (B). n: sample count. n.s.: non-significant.
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The work was financially supported by the University of Pécs, Medical School, Hungary grant (KA-2018-17) and was also supported by the EFOP 3.6.1-16-2016-00004 project (Comprehensive Development for Implementing Smart Specialization Strategies) of the University of Pécs. Bálint Nagy was supported by the Thematic Excellence Program 2020—National Excellence Subprogram; Biomedical Engineering Project (“2020-4.1.1-TKP2020”) of the University of Pécs. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Fig 2. Urinary actin in sepsis-related AKI.
Fig 2. Urinary actin in sepsis-related AKI.
U-actin (A) and u-actin/u-creatinine (B) levels of the individual sepsis-related AKI stages during follow-up. n: sample count. *p

Fig 3. Survival and predictive power of…

Fig 3. Survival and predictive power of urinary actin.

U-actin levels in survivor and non-survivor…

Fig 3. Survival and predictive power of urinary actin.
U-actin levels in survivor and non-survivor septic patients based on 30-day mortality during follow-up (A). Receiver operating characteristic (ROC) curves of admission laboratory parameters for distinguishing sepsis from sepsis-related AKI (B). n: sample count. n.s.: non-significant.
Fig 3. Survival and predictive power of…
Fig 3. Survival and predictive power of urinary actin.
U-actin levels in survivor and non-survivor septic patients based on 30-day mortality during follow-up (A). Receiver operating characteristic (ROC) curves of admission laboratory parameters for distinguishing sepsis from sepsis-related AKI (B). n: sample count. n.s.: non-significant.

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