Biomarkers for the diagnosis of sepsis-associated acute kidney injury: systematic review and meta-analysis

Background: With the development of new techniques, blood and other humoral biomarkers have become increasingly important in the diagnosis of sepsis-associated acute kidney injury (AKI). We aimed to review and summarize the biomarkers associated with the diagnosis of sepsis-associated AKI. Methods: We performed a systematic review in PubMed, Embase, Web of Science, Cochrane and CNKI literature databases. Chinese and English articles published before January 30, 2021. We extracted information on the sensitivity and specificity of biomarkers to diagnose sepsis-associated AKI, the sample size of individuals with sepsis-associated AKI, the demographic variables, the diagnostic criteria and the sample acquisition protocol. Revman 5.3 software was used to analyze data. The sources of heterogeneity of included studies main were different diagnostic criteria for sepsis and AKI, time of sample collection and Patients came from different departments. We defined the inclusion of related studies by using PICOs (Patient, Intervention, Comparison and Outcome) criteria, in particular the design of studies to be included. P: Patients of sepsis. I: Patients of sepsis-associated AKI. C: Patients without sepsis-associated AKI. O: Diagnosis of sepsis associated kidney injury. Results: A total of 1,227 articles, including 42 studies, were identified. Increases in urine and serum neutrophil gelatinase-related lipid carrier protein (NGAL), urinary interleukin-18, urinary Kim-1, urinary netrin-1, urinary sCD163, serum estradiol levels, and serum soluble thrombolytic regulatory protein were most strongly correlated with the diagnosis of sepsis-associated AKI. The SROC of urinary KIM-1 ranked first, followed by the other biomarkers: urinary KIM-1 > urinary NGAL > blood NGAL > urinary IL-18. According to the sample size, the SROC values of urinary NGAL, blood NGAL, urinary IL-18 and urinary KIM-1 were 0.907, 0.857, 0.861 and 0.931, respectively. The sequence was still urinary KIM-1 > urinary NGAL > blood NGAL > urinary IL-18. Conclusions: According to the SROC curve area, the diagnostic sequence of sepsis-associated AKI biomarkers was urinary Kim-1 > urinary NGAL > blood NGAL > urinary IL-18. This meta-analysis provided diagnostic features of blood and urine biomarkers based on their association with the diagnosis of sepsis-associated AKI.