Urinary Actin, as a Potential Marker of Sepsis-related Acute Kidney Injury

Urinary Actin, as a Potential Marker of Sepsis-related Acute Kidney Injury: a Pilot Study

In our study, 17 septic, 43 sepsis-related acute kidney injury and 24 control patients were enrolled. Blood and urine samples were collected at the intensive care unit from acutely diagnosed septic and sepsis-related acute kidney injury 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. Not more than one sample (venous blood, midstream spot urine) was collected from control patients. Serum and urinary actin levels were determined by quantitative Western blot. Urinary actin concentrations were expressed as µg/L, while serum actin levels were expressed as mg/L. Data were compared with laboratory and clinical parameters. Patients were categorized by the Sepsis-3 definitions and 30-day mortality data were investigated.

Study Overview

• Status: Completed
• Conditions: Sepsis; Acute Kidney Injury Due to Sepsis
• Intervention / Treatment: Other: Sepsis therapy; Other: Sepsis-related acute kidney injury therapy

Detailed Description

Actin is a globular protein present in every cell with a 42 kilodalton molecular mass. It plays an important role in muscle contraction while being an essential component of the cytoskeleton as well. Several proteins (e.g. gelsolin, Gc-globulin) bind actin in the circulation during the physiological cell turnover, thus making its urinary appearance unlikely. However, recent studies indicate that actin could be detected in the urine of kidney-transplant patients with acute kidney injury. Therefore, the main focus of our research was the detection and measurement of actin in the blood and urine in patients with sepsis or sepsis-related acute kidney injury, as the early recognition of kidney injury - especially in sepsis - is essential in the aspect of therapy and survival.

• Study Type: Observational
• Enrollment (Actual): 84

Contacts and Locations

Study Locations

• Hungary
  • Baranya
    • Pécs, Baranya, Hungary, 7624
      • Department of Anesthesiology and Intensive Therapy, Medical School, University of Pécs

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Diagnosed septic or sepsis-related acute kidney injury patients

Description

Inclusion Criteria:

• Sepsis
• Sepsis-related acute kidney injury

Exclusion Criteria:

• malignancies needing palliative care
• end-stage renal disease
• kidney transplantation
• under 18 years of age
• unobtainable consent

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Sepsis; Patients receive sepsis therapy.	Other: Sepsis therapy; Patients receiving sepsis therapy followed the international guidelines of the 2016 Surviving Sepsis Campaign regarding fluid resuscitation, feeding, vasopressor, respiratory, anticoagulation and hydrocortisone therapy, along with ulcer prophylaxis and sedation. Blood and urine samples were collected at the intensive care unit from this patient group at three time points (T1-3): T1: within 24 hours after admission; T2: second day morning; T3: third day morning of follow-up. 24 patients were documented without sepsis and acute kidney injury as a control group.
Sepsis-related acute kidney injury; Patients receive sepsis and sepsis-related acute kidney injury therapy.	Other: Sepsis-related acute kidney injury therapy; Patient management of sepsis and sepsis-related acute kidney injury followed the international guidelines of the 2016 Surviving Sepsis Campaign regarding fluid resuscitation, feeding, vasopressor, respiratory, anticoagulation and hydrocortisone therapy, along with ulcer prophylaxis, sedation and renal replacement therapy (if needed). In this patient group, blood and urine sampling was performed at three time points (T1-3): T1: within 24 hours after admission; T2: second day morning; T3: third day morning of follow-up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary actin concentrations	Urine samples were centrifuged (10 min, 1500 g) and supernatants were treated with electrophoresis sample buffer then heated at 100 °C for 5 minutes. Urinary actin was determined by quantitative Western blot. Native and denatured sample aliquots were stored at -70 °C until analysis.	3 days
Serum actin concentrations	Clotted blood samples were centrifuged (10 min, 1500 g) and supernatants were treated with electrophoresis sample buffer then heated at 100 °C for 5 minutes. Serum actin was determined by quantitative Western blot. Native and denatured sample aliquots were stored at -70 °C until analysis.	3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
U-actin/u-creatinine concentrations	U-actin values were determined by quantitative Western blot, while U-creatinine concentrations were measured using automated routine laboratory procedures, therefore U-actin/u-creatinine ratios could be calculated.	5 days

Collaborators and Investigators

• Sponsor: University of Pecs
• Investigators: Principal Investigator: Beáta Bugyi, MD, PhD, Department of Biophysics, Medical School, University of Pécs; Principal Investigator: Andrea Ludány, MD, PhD, Department of Laboratory Medicine, Medical School, University of Pécs; Principal Investigator: Bálint Nagy, MD, PhD, Department of Anesthesiology and Intensive Therapy, Medical School, University of Pécs; Study Director: Diána Mühl, MD, PhD, Department of Anesthesiology and Intensive Therapy, Medical School, University of Pécs

Publications and helpful links

General Publications

• Ragan D, Kustan P, Horvath-Szalai Z, Szirmay B, Bugyi B, Ludany A, Miseta A, Nagy B, Muhl D. Urinary actin, as a potential marker of sepsis-related acute kidney injury: A pilot study. PLoS One. 2021 Jul 26;16(7):e0255266. doi: 10.1371/journal.pone.0255266. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2016
• Primary Completion (ACTUAL): December 31, 2019
• Study Completion (ACTUAL): December 31, 2019

Study Registration Dates

• First Submitted: July 8, 2021
• First Submitted That Met QC Criteria: July 8, 2021
• First Posted (ACTUAL): July 20, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 9, 2021
• Last Update Submitted That Met QC Criteria: August 1, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Acute Kidney Injury; Sepsis-3; Urinary actin; Western blot
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Kidney Diseases; Urologic Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Renal Insufficiency; Sepsis; Toxemia; Wounds and Injuries; Acute Kidney Injury
• Other Study ID Numbers: no. 4327.316-2900/KK15/2011; KA-2018-17 (OTHER_GRANT: Medical School, University of Pécs)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No