Marker related to acute kidney injury related to sepsis

Abstract

The invention discloses a marker related to acute kidney injury related to sepsis. According to the application, the content of Xanthosine in healthy patients, sepsis-related acute kidney injury patients and sepsis-non-acute kidney injury patients is found to have significant difference for the first time, verification of different samples is carried out, and two data sets have relatively high diagnosis efficiency; the discovery of the application provides a new thought for early diagnosis and effective intervention of patients with sepsis-related acute kidney injury, and has a wide application prospect.

Description

Technical Field

[0001] This invention belongs to the field of biomedicine, specifically relating to biomarkers for sepsis-related acute kidney injury. Background Technology

[0002] Sepsis is currently a common disease and a significant global public health problem, causing 5.3 million deaths annually, with an overall mortality rate of approximately 30%, and even higher mortality rates in intensive care units. Sepsis-associated acute kidney injury (SA-AKI) is a common complication in critically ill patients, often associated with high morbidity and mortality, with its severity directly proportional to the risk of death.

[0003] Therefore, early diagnosis of SA-AKI can provide clinicians with practical guidance for clinical decision-making, and is crucial for supporting treatment and limiting the further development of the disease. Summary of the Invention

[0004] To overcome the shortcomings of the prior art, the present invention provides biomarkers related to sepsis-associated acute kidney injury.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: The first aspect of the present invention provides the use of a reagent for detecting Xanthosine levels in a sample in the preparation of products for differentiating sepsis from sepsis-associated acute kidney injury and for diagnosing sepsis-associated acute kidney injury.

[0006] Furthermore, the samples include blood and urine.

[0007] Furthermore, the reagents include those for detecting the concentration or content of Xanthosine in a sample by targeted or non-targeted nuclear magnetic resonance, chromatography, spectroscopy, mass spectrometry, chemical analysis, or combinations thereof.

[0008] Furthermore, when the level of Xanthosine in the subjects increased significantly, the subjects had sepsis-related acute kidney injury or were at risk of sepsis-related acute kidney injury.

[0009] A second aspect of the present invention provides a product for distinguishing between sepsis and sepsis-associated acute kidney injury and for diagnosing sepsis-associated acute kidney injury, the product comprising a reagent for detecting Xanthosine levels in a sample.

[0010] Furthermore, the product includes a reagent kit, a chip, or a test strip.

[0011] Furthermore, the kit also includes one or more of the following: reagents for processing samples, standards, buffers, and instructions.

[0012] A third aspect of the invention provides the application of Xanthosine in constructing computational models for distinguishing between sepsis and sepsis-associated acute kidney injury, and for diagnosing sepsis-associated acute kidney injury.

[0013] A fourth aspect of the invention provides the use of Xanthosine as a target in screening candidate drugs for the treatment of sepsis-related acute kidney injury.

[0014] Furthermore, a method for screening candidate drugs for treating sepsis-related acute kidney injury includes: treating a culture system containing Xanthosine with a substance to be screened; and detecting the level or content of Xanthosine in the system; wherein, when the substance to be screened reduces the level or content of Xanthosine, the substance to be screened is a candidate drug for treating sepsis-related acute kidney injury.

[0015] A fifth aspect of the present invention provides a system for distinguishing between sepsis and sepsis-associated acute kidney injury, and for diagnosing sepsis-associated acute kidney injury, the system comprising: Data acquisition unit: Acquire Xanthosine level data in the sample; Data classification unit: Comparing Xanthosine level data with reference values; Output unit: Outputs and stores analysis results, indicating whether the subject has sepsis-related acute kidney injury or is at risk of developing sepsis-related acute kidney injury.

[0016] Furthermore, when the Xanthosine level is higher than the reference value, the result indicates that the subject has sepsis-related acute kidney injury or is at risk of developing sepsis-related acute kidney injury.

[0017] Advantages and beneficial effects of the present invention: This application is the first to discover significant differences in the levels of Xanthosine among healthy patients, patients with sepsis-related acute kidney injury, and patients with non-acute sepsis-related kidney injury. The findings were validated on different samples, and both datasets demonstrated high diagnostic efficacy. This discovery provides a new approach for the early diagnosis and effective intervention of patients with sepsis-related acute kidney injury and has broad application prospects. Attached Figure Description

[0018] Figure 1 This is a graph showing the Xanthosine content in the training set; Figure 2 This is the ROC curve of Xanthosine in the training set plasma; Figure 3 This is a PRC plot of Xanthosine in the training set plasma; Figure 4This is a correlation analysis diagram verifying the detection of Xanthosine using liquid chromatography-tandem mass spectrometry and quantitative methods; Figure 5 This is a graph validating the detection of Xanthosine content using liquid chromatography-tandem mass spectrometry. Figure 6 This is a graph showing the Xanthosine content detected by the validation set quantitative method; Figure 7 This is to verify the plasma Xanthosine ROC curve obtained by liquid chromatography-tandem mass spectrometry. Figure 8 This is to verify the plasma Xanthosine PRC chromatogram obtained by liquid chromatography-tandem mass spectrometry. Figure 9 This is the validation set quantitative plasma Xanthosine ROC curve; Figure 10 This is a validation set quantitative plasma Xanthosine PRC plot. Detailed Implementation

[0019] The following provides definitions for some of the terms used in this specification. Unless otherwise stated, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0020] This invention provides the application of a reagent for detecting Xanthosine levels in a sample in the preparation of products that differentiate between sepsis and sepsis-associated acute kidney injury and for the diagnosis of sepsis-associated acute kidney injury.

[0021] In some embodiments, the sample is a biological sample. Biologically derived samples (i.e., biological samples) typically contain a variety of metabolites. Preferred experimental samples in this application are derived from bodily fluids, preferably from blood, plasma, serum, feces, lymph, sweat, saliva, tears, semen, vaginal fluid, urine, or cerebrospinal fluid, or from samples of cells, tissues, or organs obtained, for example, through vivisection. Techniques for obtaining these different types of biological samples are well known in the art. For example, blood samples are obtained through blood collection, urine samples through urine collection, and fecal samples through fecal collection.

[0022] In some embodiments, the level (or content) of the metabolite Xanthosine may be one or more of the following: the absolute or relative amount or concentration of the metabolite; the presence or absence of the metabolite; the range of the amount or concentration of the metabolite; the minimum and / or maximum amount or concentration of the metabolite; the average amount or concentration of the metabolite; and / or the median amount or concentration of the metabolite.

[0023] In a preferred embodiment, the sample is selected from blood or urine.

[0024] The reagents also include reagents for detecting the concentration or content of the metabolites in a sample by targeted or non-targeted nuclear magnetic resonance, chromatography, spectroscopy, mass spectrometry, chemical analysis, or combinations thereof.

[0025] In some embodiments, the chromatographic method includes gas chromatography, liquid chromatography, high-performance liquid chromatography, and ultra-high-performance liquid chromatography.

[0026] In some embodiments, the spectroscopic method includes ultraviolet-visible spectroscopy, infrared spectroscopy, near-infrared spectroscopy, and nuclear magnetic resonance spectroscopy.

[0027] In some embodiments, the mass spectrometry methods include, for example, tandem mass spectrometry, matrix-assisted laser desorption / ionization (MALDI) time-of-flight (TOF) mass spectrometry, MALDI-TOF-TOF mass spectrometry, MALDI quadrupole-time-of-flight (Q-TOF) mass spectrometry, electro-jet ionization (ESI) TOF mass spectrometry, ESI-Q-TOF, ESI-TOF-TOF, ESI-ion trap mass spectrometry, ESI triple quadrupole mass spectrometry, ESI Fourier transform mass spectrometry (FTMS), MALDI-FTMS, MALDI-ion trap-TOF, and ESI-ion trap-TOF. At its most basic level, mass spectrometry involves ionizing molecules and subsequently measuring the mass of the resulting ions. Because molecules ionize in a known manner, the molecular weight of the molecule can be precisely determined from the mass of the ions. Chromatography-mass spectrometry, also known as liquid chromatography-mass spectrometry, combines the physical separation capabilities of liquid chromatography (LC) or high-performance liquid chromatography (HPLC) with the mass spectrometry (MS) capabilities. HPLC offers advantages over LC, including shorter analysis times and better resolution for analytes. This, in turn, increases the selectivity, precision, and accuracy of MS.

[0028] When the level of Xanthosine in a subject increases significantly, the subject is at risk of sepsis-associated acute kidney injury or sepsis-associated acute kidney injury.

[0029] In some implementations, when reference results are obtained from subjects or populations known not to have sepsis-related acute kidney injury, the disease or susceptibility can be diagnosed based on the difference between the test results obtained from the sample and the aforementioned reference results, i.e., based on a qualitative or quantitative difference in Xanthosine. The difference can be an increase in the absolute or relative amount of Xanthosine (also known as Xanthosine upregulation) or a decrease in the amount of Xanthosine or an undetectable amount (also known as Xanthosine downregulation). Preferably, the difference in relative or absolute amount is significant, i.e., outside the reference ranges of the 45th to 55th percentile, 40th to 60th percentile, 30th to 70th percentile, 20th to 80th percentile, 10th to 90th percentile, and 5th to 95th percentile.

[0030] The products include reagent kits, chips, or test strips.

[0031] In some embodiments, in addition to metabolite standards, the kit preferably further includes preservatives or buffers for storage. Furthermore, the kit may include instructions for use.

[0032] In some embodiments, the components of the kit may be packaged in an aqueous medium or in a lyophilized form. Suitable containers in the kit typically include at least one vial, test tube, long-necked flask, syringe, or other container in which one component can be placed, and preferably, the component can be suitably aliquoted. When more than one component is present in the kit, the kit will also typically include a second, third, or other additional container in which the additional components are placed separately. However, different combinations of components may be contained in a single vial. The kit of the present invention will also typically include a container for containing the reactants, sealed for commercial sale. Such a container may include injection-molded or blow-molded plastic containers in which the desired vials can be held.

[0033] This invention provides a system for differentiating sepsis from sepsis-associated acute kidney injury and for diagnosing sepsis-associated acute kidney injury, the system comprising: Data acquisition unit: Acquire Xanthosine level data in the sample; Data classification unit: Comparing Xanthosine level data with reference values; Output unit: Outputs and stores analysis results, indicating whether the subject has sepsis-related acute kidney injury or is at risk of developing sepsis-related acute kidney injury.

[0034] In some embodiments, the system involves different tools that are effectively connected to each other. These tools may be implemented in a single device or may be physically separate devices that are effectively connected to each other. The tool for comparing the characteristic values ​​of metabolites (xanthosine) preferably operates based on an algorithm used for comparison. The data storage medium preferably contains the aforementioned dataset or database, wherein each set of stored data indicates sepsis-associated acute kidney injury or its susceptibility. Therefore, the system of this application allows for the identification of whether a dataset stored in the data storage medium contains a set of experimental data. As a result, the system of this application can be used as a diagnostic tool for diagnosing sepsis-associated acute kidney injury or its susceptibility. In a preferred embodiment of the system, a tool for measuring the characteristic values ​​of sample metabolites is included.

[0035] In some embodiments, the tool used to determine the characteristic values ​​of metabolites preferably involves a mass spectrometry device, an NMR device, or a device for determining metabolites chemically or biologically.

[0036] The invention is further illustrated below with reference to specific embodiments. It should be understood that the specific embodiments described herein are by way of example and are not intended to limit the invention. The main features of the invention can be used in various embodiments without departing from the scope of the invention.

[0037] Example 1. Experimental Materials and Results Training set: A retrospective clinical study was conducted in the Department of Critical Care Medicine, Second Affiliated Hospital of Harbin Medical University, from August 2022 to March 2023, involving 98 patients (34 SA-AKI patients vs. 64 non-SA-AKI sepsis patients). Inclusion criteria included: (1) age 18–65 years; (2) sepsis patients meeting the Sepsis-3 criteria; and (3) SA-AKI patients meeting the KDIGO diagnostic criteria, i.e., an increase in serum creatinine ≥0.3 mg / dL (>26.5 μmol / L) or more than 1.5 times the baseline value within 48 hours. Exclusion criteria included: (1) discharge or death within 24 hours of ICU admission; (2) coexisting malignancy; (3) presence of immunodeficiency or autoimmune disease; and (4) incomplete clinical data. All relevant clinical data were collected according to standardized protocols.

[0038] Peripheral venous blood and urine samples were collected from patients on the first day of diagnosis. After centrifugation at 3000 rpm for 15 minutes, 100 µl of the supernatant was immediately flash-frozen in liquid nitrogen and then stored at -80°C. This study was approved by the Ethics Committee of the Second Affiliated Hospital of Harbin Medical University (Approval No.: KY2021-188) and strictly followed the ethical guidelines of the Declaration of Helsinki.

[0039] Results: The training set included 98 samples, of which 64 were non-SA-AKI and 34 were SA-AKI. Analysis revealed that plasma xanthosine levels were significantly higher in the SA-AKI group than in the non-SA-AKI group. Figure 1 The diagnostic analysis of plasma xanthosine for SA-AKI showed an ROC of 0.779 (0.678-0.880). Figure 2 ), PRC is 0.657 (0.470-0.812) ( Figure 3 ).

[0040] Validation set: A clinical cohort including sepsis patients and healthy volunteers was recruited at the First Affiliated Hospital of Harbin Medical University from June 2023 to December 2024. Inclusion criteria included: (1) age 18–65 years; (2) sepsis patients meeting the Sepsis-3 criteria; (3) SA-AKI patients meeting the KDIGO diagnostic criteria, i.e., an increase in serum creatinine ≥0.3 mg / dL (>26.5 μmol / L) or more than 1.5 times the baseline value within 48 hours. Exclusion criteria included: (1) discharge or death within 24 hours of ICU admission; (2) coexisting malignancy; (3) presence of immunodeficiency or autoimmune disease; (4) incomplete clinical data. All relevant clinical data were collected according to standardized protocols. This study was approved by the Ethics Committee of the First Affiliated Hospital of Harbin Medical University (Approval No.: 2023125) and strictly followed the ethical principles of the Declaration of Helsinki.

[0041] Results: The validation set included 145 plasma samples, comprising 20 healthy volunteers, 35 non-SA-AKI cases, and 90 SA-AKI cases. Analysis revealed a high correlation between xanthine nucleotide content obtained from liquid chromatography-tandem mass spectrometry (LC-MS / MS) and quantitative methods within the same sample (R = 0.76, p < 0.05, Spearman). Figure 4 In both detection methods, the plasma xanthine nucleoside content gradually increased from the HC group to the Non-SA-AKI group and then to the SA-AKI group. The content in the SA-AKI group was much higher than that in the HC group and the Non-SA-AKI group. Figure 5 , Figure 6 Plasma Xanthosine diagnostic analysis for SA-AKI showed an AUC of 0.757 (0.656-0.857) obtained by LC-MS. Figure 7 The PRC is 0.876 (0.794-0.934). Figure 8The AUC obtained by the Quantitative method is 0.852 (0.774-0.929). Figure 9 The PRC is 0.933 (0.880-0.969). Figure 10 The diagnostic value analysis data are shown in Table 1.

[0042] Table 1. Diagnostic value analysis of Xanthosine

[0043] 2. Experimental Methods Detection methods: Quantitative methods were used for detection in the training and validation sets, and liquid chromatography-tandem mass spectrometry (LC-MS / MS) was used for detection in the validation set. LC-MS / MS is a semi-quantitative method. Xanthine nucleosides are hydrophilic compounds.

[0044] Liquid chromatography-tandem mass spectrometry (LC-MS / MS): Extraction method for hydrophilic compounds: Thaw the sample stored at -80 °C on ice and vortex for 10 seconds. Add 50 μL of sample and 300 μL of extraction solution containing internal standard (acetonitrile:methanol = 1:4, v / v) to a 2 mL microcentrifuge tube. Vortex for 3 minutes, then centrifuge at 4 °C and 12,000 rpm for 10 minutes. Freeze 200 μL of the supernatant at -20 °C for 30 minutes, then centrifuge again at 4 °C and 12,000 rpm for 3 minutes. Transfer 180 μL of the supernatant for LC-MS analysis.

[0045] UPLC conditions for hydrophilic compounds (UPLC: Ultra Performance Liquid Chromatography): Sample extracts were analyzed using an LC-ESI-MS / MS system (UPLC model: ExionLC AD, https: / / sciex.com.cn / ; mass spectrometer model: QTRAP® system, https: / / sciex.com / ). The analytical conditions were as follows: one aliquot of the sample was analyzed in positive ion mode using a T3 column (Waters ACQUITY UPLC HSS T3 C18, 1.8 µm, 2.1 mm × 100 mm). Mobile phase A consisted of an aqueous solution containing 0.1% formic acid, and mobile phase B consisted of an acetonitrile solution containing 0.1% formic acid. The gradient elution program was as follows: phase B increased from 5% to 20% within 2 minutes, then increased to 60% within 3 minutes, increased to 99% within 1 minute and held for 1.5 minutes, then recovered to 5% phase B within 0.1 minutes and equilibrated for 2.4 minutes. The analytical parameters were as follows: column temperature 40 °C; flow rate 0.4 mL / min; injection volume 2 μL. The data acquisition instrument system mainly included ultra-high performance liquid chromatography (UPLC) (ExionLC AD, https: / / sciex.com.cn / ) and tandem mass spectrometry (MS / MS) (QTRAP®, https: / / sciex.com / ).

[0046] QTOF-MS / MS Analysis: Information-dependent acquisition mode was used, and data was acquired through Analyst TF 1.7.1 software. Ion source parameters were set as follows: Ion source gas 1 pressure 50 psi; Ion source gas 2 pressure 50 psi; curtain gas pressure 25 psi; temperature 550 °C; declustering voltage positive / negative modes 60 V / -60 V; ion spray voltage positive / negative modes 5000 V / -4000 V. TOF MS full scan parameters: mass range 50–1000 Da; accumulation time 200 ms; dynamic background subtraction enabled. Femtoion scan parameters: mass range 25–1000 Da; accumulation time 40 ms; collision energy positive / negative modes 30 V / -30 V; collision energy spread 15; resolution mode UNIT; charge state setting 1 to 1; intensity threshold 100 cps; exclusion of isotope peaks within 4 Da; mass tolerance 50 ppm; maximum candidate ion monitoring per cycle 18.

[0047] ESI-Q TRAP-MS / MS of hydrophilic compounds: A triple quadrupole-linear ion trap mass spectrometry system equipped with an ESI Turbo Ion-Spray interface was used for positive and negative ion mode scanning under the control of Analyst 1.6.3 software. ESI source parameters: ion source temperature 500 °C; spray voltage 5500 V / -4500 V for positive and negative modes, respectively; ion source gas I, gas II, and curtain gas pressures set to 55 psi, 60 psi, and 25.0 psi, respectively; collision gas in high flow rate mode. The instrument was calibrated for QQQ and LIT modes using 10 μmol / L and 100 μmol / L polypropylene glycol solutions, respectively. Specific MRM ion pairs were monitored based on the metabolites eluted at each time point.

[0048] Xanthine nucleoside qualitative analysis: Equal volumes of all sample extracts were mixed to form QC samples, and non-targeted detection was performed on the LC-QTOF-MS / MS platform. Accurate qualitative analysis was performed based on the self-built standard database MWDB (including secondary spectra and retention time RT), the Maiwei integrated DB-all public database (including databases such as Metlin, HMDB, and KEGG), the AI ​​prediction library, and MetDNA. Information such as multiple ion pairs and retention time RT of the identified metabolites were also extracted.

[0049] Quantitative methods for detecting xanthine nucleosides Metabolite extraction: After thawing the sample on ice, vortex for 10 seconds to mix. Accurately pipette 50 μL of sample (remaining sample should be immediately returned to -80℃ for storage) into a corresponding numbered 1.5 mL centrifuge tube, and add 250 μL of pre-chilled 20% acetonitrile-methanol extraction buffer. Vortex for 3 minutes to mix thoroughly, then centrifuge at 4℃ and 12000 r / min for 10 minutes. After centrifugation, transfer 250 μL of the supernatant to another pre-numbered 1.5 mL centrifuge tube and incubate at -20℃ for 30 minutes. After incubation, centrifuge again at 4℃ and 12000 r / min for 10 minutes. Finally, collect 180 μL of the supernatant, filter it through a protein precipitation plate, transfer it to the sample vial for analysis, and store at -20℃ until analysis.

[0050] Chromatographic and mass spectrometric acquisition conditions (T3 method HPLC conditions): Data acquisition was performed using an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS / MS) system, consisting of an ExionLC™ AD UHPLC system and a QTRAP® 6500+ tandem mass spectrometer (SCIEX). Chromatographic separation was performed using a Waters ACQUITY UPLC HSS T3 C18 column (1.8 µm, 100 mm × 2.1 mm). The mobile phase consisted of an aqueous solution containing 0.05% formic acid (phase A) and an acetonitrile solution containing 0.05% formic acid (phase B). The flow rate was 0.35 mL / min, the column temperature was 40°C, and the injection volume was 2 µL. The gradient elution program was set as follows: at 0 min, the A / B ratio was 95:5 (V / V); at 8 min, it was adjusted to 5:95; at 12.5 min, it remained at 5:95; at 12.6 min, it returned to 95:5 and continued until 15 min.

[0051] Qualitative and quantitative analysis of xanthine nucleosides: The MWDB (Metware Database) was constructed based on standards to perform qualitative analysis on the mass spectrometry data.

[0052] Quantitative analysis was performed using the multiple reaction monitoring (MRM) mode of triple quadrupole mass spectrometry (MMS, as shown in the figure below). In MRM mode, the quadrupole first screens for precursor ions (parent ions) of the target substance, excluding ions corresponding to other molecular weight substances to initially eliminate interference. After the precursor ions are induced to ionize in the collision chamber, they break into multiple fragment ions. These fragment ions are then filtered by the triple quadrupole to select the desired characteristic fragment ions, eliminating interference from non-target ions, making the quantification more accurate and reproducible. After obtaining mass spectrometry analysis data for different samples, the chromatographic peaks of all target substances are integrated, and quantitative analysis is performed using a standard curve.

[0053] Standard curve: Prepare standard solutions of different concentrations (0.01 ng / mL, 0.02 ng / mL, 0.05 ng / mL, 0.1 ng / mL, 0.2 ng / mL, 0.5 ng / mL, 1 ng / mL, 2 ng / mL, 5 ng / mL, 10 ng / mL, 20 ng / mL, 50 ng / mL, 100 ng / mL, 200 ng / mL, 500 ng / mL, 1000 ng / mL, 2000 ng / mL, 5000 ng / mL, 1000 ng / mL, 2000 ng / mL, 5000 ng / mL, 10000 ng / mL) and obtain the chromatographic peak intensity data of the corresponding quantitative signals for each concentration of standard. Plot the standard curve of xanthine nucleoside with the external standard to internal standard concentration ratio or external standard concentration as the x-axis and the external standard to internal standard peak area ratio or external standard peak area as the y-axis. Training set: y = 4183.57514 x - 6462.65354, R = 0.99653 (correlation coefficient of the standard curve) Validation set: y = 3.52929e4x - 13613.97845, R = 0.99985 (correlation coefficient of the standard curve) Content Calculation: The content (ng / mL) of each substance in the sample is calculated according to the following formula: Content = (c×V1) / (1000×V2). Where c is the concentration value (ng / mL) calculated from the sample integrated peak area using the standard curve, V1 is the total volume of the extract (μL), and V2 is the sample volume transferred (mL).

[0054] The above description of the embodiments is only for understanding the method and core ideas of the present invention. It should be noted that those skilled in the art can make various improvements and modifications to the present invention without departing from the principles of the invention, and these improvements and modifications will also fall within the protection scope of the claims of the present invention.

Claims

1. Application of reagents for detecting Xanthosine levels in samples in the preparation of products that differentiate between sepsis and sepsis-associated acute kidney injury and for the diagnosis of sepsis-associated acute kidney injury.

2. The application according to claim 1, characterized in that, The samples included blood and urine.

3. The application according to claim 1, characterized in that, The reagents include those for detecting the concentration or content of Xanthosine in a sample by targeted or non-targeted nuclear magnetic resonance, chromatography, spectroscopy, mass spectrometry, chemical analysis, or combinations thereof.

4. The application according to any one of claims 1-3, characterized in that, When the level of Xanthosine in a subject increases significantly, the subject is at risk of sepsis-associated acute kidney injury or sepsis-associated acute kidney injury.

5. A product for differentiating between sepsis and sepsis-related acute kidney injury, and for diagnosing sepsis-related acute kidney injury, characterized in that, The product includes reagents for detecting Xanthosine levels in samples.

6. The product according to claim 5, characterized in that, The products include reagent kits, chips, or test strips.

7. The product according to claim 6, characterized in that, The kit also includes one or more of the following: reagents for processing samples, standards, buffers, and instructions.

8. Application of Xanthosine in constructing computational models to distinguish between sepsis and sepsis-associated acute kidney injury and to diagnose sepsis-associated acute kidney injury.

9. Application of Xanthosine as a target in screening candidate drugs for the treatment of sepsis-related acute kidney injury; Preferably, the method for screening candidate drugs for treating sepsis-related acute kidney injury includes: The culture system containing Xanthosine is treated with a substance to be screened; and the level or content of Xanthosine in the system is detected; wherein, when the substance to be screened reduces the level or content of Xanthosine, the substance to be screened is a candidate drug for the treatment of sepsis-related acute kidney injury.

10. A system for distinguishing between sepsis and sepsis-related acute kidney injury, and for diagnosing sepsis-related acute kidney injury, characterized in that, The system includes: Data acquisition unit: Acquire Xanthosine level data in the sample; Data classification unit: Comparing Xanthosine level data with reference values; Output unit: Outputs and stores analysis results, indicating whether the subject has sepsis-related acute kidney injury or is at risk of developing sepsis-related acute kidney injury.

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