MULTIMODAL APPROACH IN THE DIAGNOSIS OF SEPTIC AKI (SEPTIC AKI)

A MULTIMODAL APPROACH TO PREDICTING SEPSIS-RELATED ACUTE RENAL INJURY: A PROSPECTIVE COHORT STUDY

In recent studies, it has been reported that the renal resistance index is effective in detecting sepsis-related acute renal failure (SA-AKI) in the early period. Similarly, urinary biomarkers [TIMP-2]*[IGFBP-7], released in response to tubular epithelial cell stress, have been reported to indicate the presence of acute renal injury (AKI) early on, before functional loss occurs (increased creatinine). This observational study aims to evaluate the renal resistance index and urinary biomarker variation in patients diagnosed with sepsis and to investigate their usefulness in the early detection of renal dysfunction that may develop after sepsis.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis; Critical Illness; Acute Kidney Injury; Renal Resistive Index
• Intervention / Treatment: Diagnostic test: Renal Resistive Index (RRI) Doppler Ultrasound; Diagnostic test: Urinary TIMP-2 and IGFBP-7 biomarkers

Detailed Description

Purpose and Rationale:

Sepsis is a life-threatening condition caused by a dysregulated host response to infection and remains a major cause of morbidity and mortality in intensive care units. Acute kidney injury (AKI) is one of the most frequent complications of sepsis and is associated with prolonged ICU and hospital stay, increased healthcare costs, and higher mortality. Early detection of renal dysfunction in septic patients is therefore crucial to improve clinical outcomes.

The diagnosis of AKI in clinical practice is mainly based on changes in serum creatinine and urine output according to KDIGO (Kidney Disease: Improving Global Outcomes) criteria. However, serum creatinine reflects functional loss of the kidney and may increase only after significant renal injury has already occurred, which may delay the diagnosis of AKI.

Recently, several physiological and biochemical markers have been investigated for earlier detection of AKI. The renal resistive index (RRI), obtained by Doppler ultrasonography of intrarenal arteries, reflects renal vascular resistance and changes in renal hemodynamics. Previous studies suggest that RRI may increase before conventional markers of kidney injury become abnormal and may help identify patients at risk of AKI during the early phase of critical illness.

In addition, urinary biomarkers reflecting tubular cellular stress have been proposed as early indicators of kidney injury. Tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) are released by renal tubular epithelial cells during cellular stress and cell cycle arrest. The combined urinary biomarker product [TIMP-2]•[IGFBP-7] has been shown to identify patients at risk for AKI before increases in serum creatinine occur.

This observational study aims to evaluate changes in renal resistive index and urinary biomarkers ([TIMP-2]*[IGFBP-7]) in patients with sepsis and to investigate their potential role in the early detection of sepsis-associated acute kidney injury.

Design:

Prospective, single-center, observational cohort study with consecutive patient enrollment over an estimated period of approximately 12-month period (or until the target sample size is reached) following ethics committee approval and study registration. Anticipated sample: 120-130 (It has been increased to prevent potential data loss.)

Participants - Eligibility:

Inclusion: Patients receiving treatment in intensive care, ≥18 years of age, diagnosed with sepsis, able to undergo RRI, and who have obtained informed consent from their legally authorized representative (or the patient).

Exclusion: End-stage renal disease (chronic RRT or eGFR <15 ml/min/1.73 m²), kidney transplant, renal artery stenosis, technical/anatomical contraindications to RRI, poor echogenicity (for RRI imaging), pregnancy.

Procedures and Timing:

Renal resistance index (RRI) will be measured by Doppler ultrasonography immediately after sepsis diagnosis (T0, baseline, first measurement), 24 hours later (T24, second measurement), and 48 hours later (T48, third measurement). RRI measurements will be taken from the interlobar arteries of both kidneys, and at least three RRI Doppler waveforms will be recorded for each kidney.

Urinary biomarker levels of [TIMP-2]•[IGFBP-7] will be measured immediately after the diagnosis of sepsis (T0) and at 24 hours after sepsis diagnosis (T24).

Renal function tests and electrolyte levels will be recorded at the time of admission to the intensive care unit (T0), and 24 hours (T24), 48 hours (T48), and 72 hours (T72) after sepsis diagnosis (every 24 hours for 72 hours).

Outcomes:

Primary: Whether sepsis-related acute renal failure (SA-AKI) develops in patients diagnosed with sepsis, and the effect of RRI and urinary [TIMP-2]•[IGFBP-7] biomarkers in predicting the development of SA-AKI.

Secondary: need for RRT up to 1 week after sepsis diagnosis, SA-AKI onset timing, ICU length of stay, and hospital length of stay.

Analysis:

Descriptives and appropriate group comparisons (AKI+ vs AKI-).

Primary model: Logistic regression → AKI (yes/no) ~ RRI_T0 (continuous and prespecified ≥0.70 threshold) + [TIMP-2]·[IGFBP-7] + covariates (age, eGFR, SOFA, vasopressors, nephrotoxins/contrast, fluid balance).

Safety and Privacy:

Ultrasound and urine sampling are not risky; the study does not direct clinical treatment.

• Study Type: Observational
• Enrollment (Estimated): 130

Contacts and Locations

• Study Contact: Name: Eda Macit Aydın, M.D., M.D.; Phone Number: +90 312 797 00 00; Email: edamct@hotmail.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Consecutive adults admitted with sepsis to the intensive care units of Etlik Şehir Hastanesi, Ankara, Türkiye. Participants will be enrolled from a single tertiary center serving a broad urban referral population. Recruitment occurs during routine ICU care, with bedside Doppler ultrasound and urine sampling scheduled per protocol; no investigator-assigned treatments are given.

Description

Inclusion Criteria:

• Adults ≥18 years
• Diagnosis of sepsis (per Sepsis-3 clinical criteria)
• RRI measurement feasible at bedside
• Informed consent from participant or legally authorized representative

Exclusion Criteria:

• End-stage kidney disease (chronic dialysis) or baseline eGFR <15mL/min/1.73 m²
• Kidney transplant recipient
• Anatomic/technical barrier precluding reliable renal Doppler (RRI) assessment
• Pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Sepsis ICU Cohort; Adult patients (≥ 18 years of age) who are admitted to the intensive care unit with sepsis or who are diagnosed with sepsis during their admission and for whom bedside renal Doppler ultrasonography is feasible will be included in the study. Participants' Renal Resistive Index (RRI) measurements will be evaluated immediately after sepsis diagnosis (T0), at 24 hours (T24), and at 48 hours (T48). Urinary [TIMP-2]*[IGFBP-7] measurements will be taken immediately after sepsis diagnosis (T0) and at 24 hours (T24). Clinical and laboratory data of the patients included in the study will be recorded for up to 72 hours after sepsis diagnosis. No treatment will be administered to the patients by the researchers; all medical care will be provided according to standard practice.

Diagnostic test: Renal Resistive Index (RRI) Doppler Ultrasound; Doppler ultrasonography will measure RRI immediately after sepsis diagnosis (T0), at 24 hours (T24), and at 48 hours (T48).; Diagnostic test: Urinary TIMP-2 and IGFBP-7 biomarkers; Urine samples for [TIMP-2]*[IGFBP-7] biomarker measurement will be collected immediately after sepsis diagnosis (T0) and 24 hours later (T24).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal resistance index (RRI)	Measurement of renal resistance index by Doppler ultrasonography immediately after sepsis diagnosis	Immediately after sepsis diagnosis (T0, baseline, first measurement)
Renal resistance index (RRI)	Measurement of renal resistance index by Doppler ultrasonography after sepsis diagnosis	24 hours after sepsis diagnosis (T24, second measurement)
Renal resistance index (RRI)	Measurement of renal resistance index by Doppler ultrasonography after sepsis diagnosis	48 hours after sepsis diagnosis (T48, third measurement)
Urine [TIMP-2]•[IGFBP-7] biomarker	Measurement of [TIMP-2]•[IGFBP-7] in urine immediately after diagnosis of sepsis	Immediately after diagnosis of sepsis (T0)
Urine [TIMP-2]•[IGFBP-7] biomarker	Measurement of [TIMP-2]•[IGFBP-7] in urine after sepsis diagnosis	24 hours after diagnosis of sepsis (T24)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to onset of sepsis-associated acute kidney injury (SA-AKI)	Time from sepsis diagnosis to the development of SA-AKI.	Up to 1 week after sepsis diagnosis
Need for Renal Replacement Therapy (RRT) After Sepsis Diagnosis	Need for renal replacement therapy modality (continuous or intermittent) in patients diagnosed with sepsis during the follow-up period.	Up to 1 week after sepsis diagnosis
Length of ICU stay	Duration of stay in the intensive care unit recorded in days from ICU admission to ICU discharge.	through study completion, an average of 1 year
Length of hospital stay	Total duration of hospitalization recorded in days from hospital admission to hospital discharge.	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Ankara Etlik City Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 30, 2026
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): January 30, 2027

Study Registration Dates

• First Submitted: February 7, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Sepsis; Intensive Care Units; Renal Resistive Index (RRI); Cell Cycle Arrest Biomarkers; Sepsis-Associated AKI
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Critical Illness; Acute Kidney Injury; Sepsis; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Imaging; Ultrasonography; Ultrasonography, Doppler
• Other Study ID Numbers: AEŞH-BADEK1-2026-025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be publicly shared due to patient privacy considerations and institutional ethics committee regulations. De-identified data may be available from the corresponding investigator upon reasonable request and with approval from the ethics committee.

Drug and device information, study documents

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