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Background: Sepsis is a complex, life-threatening clinical syndrome that can cause other related diseases, such as acute kidney injury (AKI). Circular RNA (circRNA) is a type of non-coding RNA with a diverse range of functions, and it plays essential roles in miRNA sponge. CircRNA plays a huge part in the development of various diseases. CircRNA and the competing endogenous RNA (ceRNA) regulatory network are unknown factors in the onset and progression of septic AKI (SAKI). This study aimed to clarify the complex circRNA-associated regulatory mechanism of circRNAs in SAKI. Methods: We collected 40 samples of whole blood of adults, including 20 cases of SAKI and 20 cases of healthy controls. Moreover, five cases were each analyzed by RNA sequencing, and we identified differentially expressed circRNA, miRNA, and mRNA (DEcircRNAs, DEmiRNAs, and DEmRNAs, respectively). All samples were from SAKI patients with intraperitoneal infection. Results: As a result, we screened out 236 DEcircRNAs, 105 DEmiRNAs, and 4065 DEmRNAs. Then, we constructed two co-expression networks based on RNA-RNA interaction, including circRNA-miRNA and miRNA-mRNA co-expression networks. We finally created a circRNA-miRNA-mRNA regulation network by combining the two co-expression networks. Functional and pathway analyses indicated that DEmRNAs in ceRNA were mostly concentrated in T cell activation, neutrophils and their responses, and cytokines. The protein-protein interaction network was established to screen out the key genes participating in the regulatory network of SAKI. The hub genes identified as the top 10 nodes included the following: ZNF727, MDFIC, IFITM2, FOXD4L6, CIITA, KCNE1B, BAGE2, PPIAL4A, USP17L7, and PRSS2. Conclusion: To our knowledge, this research is the first study to describe changes in the expression profiles of circRNAs, miRNAs, and mRNAs in patients with SAKI. These findings provide a new treatment target for SAKI treatment and novel ideas for its pathogenesis.
RESUMO
OBJECTIVE: To investigate the value of renal artery resistance index (RRI) and urinary angiotensinogen (UAGT) in the early diagnosis of acute kidney injury (AKI) in patients with sepsis. METHODS: A prospective study was conducted. Seventy-eight patients with sepsis admitted to the department of critical care medicine of General Hospital of Ningxia Medical University from January to September 2021 were enrolled. Patients were observed for the development of AKI within 1 week. General data [gender, age, body mass index (BMI), major infection sites and critical illness related scores], laboratory indicators [mean arterial pressure (MAP), central venous pressure (CVP), procalcitonin (PCT), arterial blood lactic acid (Lac), etc.], duration of mechanical ventilation and length of intensive care unit (ICU) stay were recorded. After hemodynamic stabilization of the patients, renal ultrasound was performed to measure the RRI within 24 hours after ICU admission. Urine samples were taken immediately after diagnosis, and the level of UAGT was detected by enzyme-linked immunosorbent assay (ELISA). The above parameters were compared between the two groups. Multivariate Logistic regression was used to analyze the risk factors of AKI in patients with sepsis. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of related indicators for AKI in sepsis. RESULTS: A total of 78 patients were finally enrolled, of which 45 developed AKI and 33 did not. Compared with the non-AKI group, the rates of vasoactive drugs use, 28-day mortality, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE II) score, PCT, Lac, RRI and UAGT were significantly higher in the AKI group [rates of vasoactive drugs use: 68.9% vs. 39.4%, 28-day mortality: 48.9% vs. 24.2%, SOFA score: 12.0 (10.5, 14.0) vs. 8.0 (7.0, 10.0), APACHE II score: 22.0 (18.0, 27.5) vs. 16.0 (15.0, 18.5), PCT (µg/L): 12.5±2.6 vs. 10.9±2.8, Lac (mmol/L): 2.6 (1.9, 3.4) vs. 1.9 (1.3, 2.6), RRI: 0.74±0.03 vs. 0.72±0.02, UAGT (µg/L): 75.16±19.99 vs. 46.28±20.75, all P < 0.05], the duration of mechanical ventilation and the length of ICU stay were significantly prolonged [duration of mechanical ventilation (days): 8.0 (7.0, 12.0) vs. 5.0 (4.0, 6.0), length of ICU stay (days): 14.0 (10.0, 16.0) vs. 9.0 (8.0, 11.5), both P < 0.01], and MAP was significantly lowered [mmHg (1 mmHg ≈ 0.133 kPa): 68.5±11.2 vs. 74.2±12.8, P < 0.05]. There was no significant difference in other parameters between the two groups. Multivariate Logistic regression analysis showed that SOFA score [odds ratio (OR) = 2.088, 95% confidence interval (95%CI) was 1.322-3.299], APACHE II score (OR = 1.447, 95%CI was 1.134-1.845), RRI (OR = 1.432, 95%CI was 1.103-1.859), and UAGT (OR = 1.077, 95%CI was 1.035-1.121) were independent risk factors for sepsis complicated with AKI (all P < 0.01). ROC curve analysis showed that SOFA score, APACHE II score, RRI and UAGT had certain predictive value for AKI in septic patients, the area under the ROC curve (AUC) were 0.814 (95%CI was 0.716-0.912), 0.804 (95%CI was 0.708-0.901), 0.789 (95%CI was 0.690-0.888), and 0.840 (95%CI was 0.747-0.934), respectively, and the AUC of RRI combined with UAGT was 0.912 (95%CI was 0.849-0.974), which was better than the above single index (all P < 0.05). CONCLUSIONS: RRI combined with UAGT has a high early predictive value for septic AKI.
