Renin Levels as Prognostic Indicators of Septic Shock Severity and Outcome

Renin Levels as Prognostic Indicators of Septic Shock Severity and Outcome: Prospective Cohort Study (SOS Trial)

The Surviving Sepsis Campaign (SSC) of 2021 characterizes sepsis as a life-threatening organ dysfunction caused by a dysregulated host response to infection, with a mortality rate of over 30%, which increases to 40% or more in the case of septic shock. Although concept of sepsis has improved, significant gaps remain in assessing its clinical severity and predicting patient outcomes.

Recognized markers of the severity of septic shock are procalcitonin (PCT), presepsin, and, to a certain extent, lactate. Elevated lactate levels result from a shift to anaerobic glycolysis and indicate inadequate oxygen delivery to tissues. Despite the importance of procalcitonin in the course of sepsis, it has proven to be a suboptimal diagnostic biomarker for the development of sepsis, with sensitivity and specificity below 80%. As a result, the use of procalcitonin in addition to clinical assessment to determine the indications for initiating antibiotic therapy is not recommended. Meanwhile, presepsin, although a potential biomarker for the early diagnosis of sepsis, also has only moderate accuracy according to current data and cannot be used as the only test for the diagnosis of sepsis.

Renin is a crucial enzyme in the renin-angiotensin-aldosterone system (RAAS), which plays an important role in the regulation of blood pressure, tissue perfusion, and the balance of water and electrolytes. Thus, renin may be the sensitive biomarker with good prognostic qualities in the context of sepsis and septic shock. Preliminary studies have indicated that elevated renin levels may act as an indicator of patient severity, and could also be used as a marker for the development of septic shock and mortality prognosis.

This study aims to address these gaps by investigating the role of renin as a biomarker for the severity of sepsis and septic shock, focusing on its potential for more accurate prediction of clinical outcomes.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Septic Shock
• Intervention / Treatment: Other: Analysis of plasma renin concentration

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Valery Likhvantsev, PhD; Phone Number: +79036235982; Email: lik0704@gmail.com
• Study Contact Backup: Name: Levan Berikashvili, PhD; Phone Number: +79263308968; Email: levan.berikashvili@mail.ru

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Recruiting
    • Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology
    • Contact: Valery Likhvantsev, PhD; Phone Number: +79036235982; Email: lik0704@gmail.com
    • Contact: Levan Berikashvili, MD; Phone Number: +79263308968; Email: levan.berikashvili@mail.ru
    • Principal Investigator: Valery Likhvantsev, PhD
    • Sub-Investigator: Levan Berikashvili, MD
    • Sub-Investigator: Ivan Kuznetsov, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with sepsis or septic shock

Description

Inclusion Criteria:

• Age ≥ 18 years
• Hospitalization in the intensive care unit
• Confirmed diagnosis of Sepsis within 24 hours
• Signed informed consent or a decision by the medical council to include the patient in the study

Exclusion Criteria:

• Any surgical intervention on the kidneys and/or adrenal glands performed within 28 days prior to the patient's inclusion in the study
• Patients previously included in this study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Septic group; Patients with sepsis or septic shock	Other: Analysis of plasma renin concentration; The concentration of plasma renin in patients will be assessed using the immunochemiluminescent method

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between blood renin concentration and norepinephrine dosage	A correlation analysis with the calculation of the correlation strength. The degree of correlation ranges from 0 to 1. The closer the correlation coefficient is to one, the stronger the correlation.	Through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between blood renin concentration and blood procalcitonin concentration	A correlation analysis with the calculation of the correlation strength. The degree of correlation ranges from 0 to 1. The closer the correlation coefficient is to one, the stronger the correlation.	Through study completion, an average of 2 years
Correlation between blood renin concentration and peripheral blood flow	A correlation analysis with the calculation of the correlation strength. The degree of correlation ranges from 0 to 1. The closer the correlation coefficient is to one, the stronger the correlation.	Through study completion, an average of 2 years
Correlation between blood renin concentration and SOFA score	A correlation analysis with the calculation of the correlation strength. The degree of correlation ranges from 0 to 1. The closer the correlation coefficient is to one, the stronger the correlation.	Through study completion, an average of 2 years
Correlation between blood renin concentration and renal replacement therapy free days	A correlation analysis with the calculation of the correlation strength. The degree of correlation ranges from 0 to 1. The closer the correlation coefficient is to one, the stronger the correlation.	Through study completion, an average of 2 years
28-days mortality	Number of deaths in period of 28 days after enrollment	28 days
Frequency of Major Adverse Kidney Events (MAKE)	Count of individuals who experience any of the following: all-cause mortality, renal replacement therapy, and acute kidney injury	28 days
Correlation between blood renin concentration and blood lactate concentration	A correlation analysis with the calculation of the correlation strength. The degree of correlation ranges from 0 to 1. The closer the correlation coefficient is to one, the stronger the correlation.	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Federal Research and Clinical Centre of Intensive Care Medicine and Rehabilitology
• Collaborators: Università Vita-Salute San Raffaele
• Investigators: Principal Investigator: Valery Likhvantsev, PhD, Federal Research and Clinical Centre of Intensive Care Medicine and Rehabilitology

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2025
• Primary Completion (Estimated): August 20, 2026
• Study Completion (Estimated): July 20, 2027

Study Registration Dates

• First Submitted: August 6, 2024
• First Submitted That Met QC Criteria: August 6, 2024
• First Posted (Actual): August 9, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Septic shock; Procalcitonin; Sepsis; Lactate; Renin
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Shock, Septic
• Other Study ID Numbers: SOS

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