Predicting Renal Replacement Therapy Requirement In Sepsis-Associated Acute Kidney Injury Using Furosemide Stress Testing and Urinary Biomarkers

Summary

This article describes a combined functional and urinary biomarker-based approach to predict renal replacement therapy requirements in patients with sepsis-associated acute kidney injury.

Abstract

This study aimed to investigate the predictive value of a model combining the furosemide stress test (FST) with urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP-7) for predicting renal replacement therapy (RRT) initiation within 7 days in patients with sepsis-associated acute kidney injury (SA-AKI). A total of 63 patients with SA-AKI admitted to the intensive care units (ICU) of Zhongwei People’s Hospital and the Affiliated Hospital of Ningxia Medical University between January 2025 and November 2025 were enrolled in this study. According to whether RRT was initiated within 7 days, patients were divided into an RRT group (n = 20) and a non-RRT group (n = 43). Clinical characteristics, laboratory parameters, and urinary biomarkers were collected. Urinary TIMP-2 and IGFBP-7 levels were measured using enzyme-linked immunosorbent assay, and the predictive performance of FST combined with urinary [TIMP-2] * [IGFBP-7] was evaluated using multivariate logistic regression and receiver operating characteristic (ROC) curve analysis. The results showed that 20 patients (31.7%) required RRT during follow-up, while 43 patients (68.3%) did not. Compared with the non-RRT group, patients in the RRT group exhibited more severe renal dysfunction and higher incidence of adverse kidney events. ROC analysis demonstrated that the area under the curve (AUC) for FST, baseline TIMP-2*IGFBP-7, TIMP-2*IGFBP-7 measured 2 h after FST, and the combined model were 0.878, 0.820, 0.845, and 0.966, respectively. Multivariate logistic regression further confirmed that the combined FST and urinary TIMP-2*IGFBP-7 indicator was an independent predictor of RRT requirement. These findings suggest that the combined FST and urinary TIMP-2*IGFBP-7 model may be useful for early risk stratification of SA-AKI patients at high risk of requiring RRT.

Introduction

Sepsis is a critical clinical syndrome commonly encountered in the intensive care unit (ICU), characterized by high morbidity and mortality. The systemic inflammatory response triggered by sepsis can lead to multiple organ dysfunction, among which sepsis-associated acute kidney injury (SA-AKI) is one of the most common and severe complications^1,2,3. Previous studies have reported that approximately 40%–50% of patients with sepsis develop SA-AKI, which is associated with significantly increased mortality^4,5,....

Protocol

Patient enrollment and ethical approval
This study was designed as a prospective two-center cohort study. The study population consisted of patients with sepsis-associated acute kidney injury (SA-AKI) who were admitted to the intensive care units (ICU) of Zhongwei People’s Hospital and the General Hospital of Ningxia Medical University between January 2025 and November 2025. The study protocol was approved by the Ethics Committees of the General Hospital of Ningxia Medical University (Approval No. KYLL-2025-1232) and Zhongwei People’s Hospital, Ningxia, China (Approval No. NXZWSRMYYLL-202445). All procedures were conducted in accorda....

Results

Patient enrollment and baseline characteristics
A total of 100 patients were initially screened in this study. After excluding 30 patients without sepsis, 5 patients with missing data, and 2 patients who withdrew from the study, a total of 63 patients with confirmed sepsis-associated acute kidney injury (SA-AKI) were finally included in the analysis. Among them, 42 were male, and 21 were female, with a mean age of 67.25 ± 14.5 years. Based on whether renal replacement therapy (RRT) was initiated with.......

Discussion

Sepsis-associated acute kidney injury (SA-AKI) is a common and severe complication in patients admitted to the intensive care unit (ICU). Its pathophysiological mechanisms are complex and involve multiple processes, including inflammatory responses, microcirculatory dysfunction, and oxidative stress¹⁸. Timely and appropriate initiation of renal replacement therapy (continuous renal replacement therapy, CRRT) is critical for improving the prognosis of patients with SA-AKI. However, the optimal timi.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Automated Biochemical Analyzer	Mindray Bio-Medical Electronics Co., Ltd., Shenzhen, China	BS-800
Biosafety Cabinet	Airtech (Suzhou) Co., Ltd., Suzhou, China	BSC-1300IIA2
Blood Gas Analyzer	Edan Instruments, Inc., Shenzhen, China	i15
Centrifuge (Low-speed refrigerated centrifuge)	Xiangyi Centrifuge Instrument Co., Ltd., Changsha, China	H1850
ELISA Kit for IGFBP-7	Elabscience Biotechnology Co., Ltd., Wuhan, China	E-EL-H5567
ELISA Kit for TIMP-2	Elabscience Biotechnology Co., Ltd., Wuhan, China	E-EL-H0003
ELISA Microplate Reader	Rayto Life and Analytical Sciences Co., Ltd., Shenzhen, China	RT-6100
ELISA Plate Washer	Rayto Life and Analytical Sciences Co., Ltd., Shenzhen, China	RT-2600C
Furosemide	Not specified in submission files	Not specified in submission files	Administered intravenously at 1.0–1.5 mg/kg for FST
Infusion Pump	Mindray Bio-Medical Electronics Co., Ltd., Shenzhen, China	BeneFusion SP5
Micropipette	Dragon Laboratory Instruments Co., Ltd., Shanghai, China	TopPette
Microplate (96-well ELISA plate)	Elabscience Biotechnology Co., Ltd., Wuhan, China	E-EL-Plate96
Multiparameter Patient Monitor	Mindray Bio-Medical Electronics Co., Ltd., Shenzhen, China	BeneVision N12
Pipette Tips (200 μL)	Dragon Laboratory Instruments Co., Ltd., Shanghai, China	T-200
R software	Not specified in submission files	Not specified in submission files	Used for statistical analyses
Refrigerated Storage (4 °C Medical Refrigerator)	Haier Biomedical Co., Ltd., Qingdao, China	HYC-290
Sterile Sample Tubes	Kangjian Medical Supplies Co., Ltd., Jiangsu, China	KJ-ST02
Ultra-Low Temperature Freezer (-80 °C)	Haier Biomedical Co., Ltd., Qingdao, China	DW-86L388
Urine Collection Tubes	Kangjian Medical Supplies Co., Ltd., Jiangsu, China	KJ-UT01