血清CITED2、BMAL1、NSUN3水平与脓毒症并发急性肾损伤患者病情的相关性及对预后的影响OA

Objective To analyze the relationship between serum levels of CBP/p300 interacting transactivator 2(CITED2),brain and muscle Arnt-like 1(BMAL1),and NOP2/Sun RNA methyltransferase 3(NSUN3)and the condition of patients with sepsis complicated by acute kidney injury(AKI),and their impact on prognosis.Methods A total of 123 pa-tients with sepsis complicated by AKI admitted to the Department of Critical Care Medicine at Tangdu Hospital,Air Force Medical University,between February 2023 and March 2025 were selected as the sepsis-AKI group.According to AKI staging criteria,cases were classified into stage Ⅰ(45 cases),stage Ⅱ(40 cases),and stage Ⅲ(38 cases).Patients were divided into a survival subgroup(81 cases)and a mortality subgroup(42 cases)based on 28-day survival status.Additionally,115 patients with uncomplicated sepsis admitted during the same period were selected as the sepsis group,and 123 healthy volunteers con-stituted the healthy control group.ELISA was used to detect serum CITED2 levels.Quantitative real-time PCR(qRT-PCR)was used to detect the relative expression levels of serum BMAL1 mRNA and NSUN3 mRNA.Pearson correlation analysis was used to examine relationships between variables.Multivariate Cox proportional hazards analysis was performed to identify factors associated with poor prognosis.Receiver operating characteristic(ROC)curve analysis was used to evaluate the predic-tive value of these biomarkers for poor prognosis in patients with sepsis complicated by AKI.Results Serum CITED2 and NSUN3 mRNA levels progressively increased across the healthy control,sepsis,and sepsis-AKI groups,while serum BMAL1 mRNA levels progressively decreased(F=544.535,728.950,478.098;all P＜0.001).Serum CITED2 and NSUN3 mRNA levels progressively increased across stages Ⅰ,Ⅱ,and Ⅲ,while serum BMAL1 mRNA levels progressively decreased(F=33.532,22.012,72.544;all P＜0.001).The mortality subgroup exhibited significantly higher serum CITED2 and NSUN3 mRNA levels,higher APACHE Ⅱ scores,higher SOFA scores,and higher serum creatinine levels compared to the survival subgroup,while serum BMAL1 mRNA levels were significantly lower(t/x2=7.514,7.639,7.732,9.627,6.264,all P＜0.001).Serum CITED2 was positively correlated with APACHE Ⅱ and SOFA scores(r=0.512,0.508,both P＜0.001);serum NSUN3 mRNA was positively correlated with APACHE Ⅱ and SOFA scores(r=0.506,0.513,both P＜0.001);and serum BMAL1 mRNA was negatively correlated with APACHE Ⅱ and SOFA scores(r=-0.527,-0.519,both P＜0.001).Elevated CITED2,NSUN3 mRNA,APACHE Ⅱ score,and SOFA score were independent risk factors for poor prognosis[HR(95％CI)=2.078(1.353-3.192),2.343(1.458-3.765),2.436(1.763-3.366),2.651(1.777-3.954)],while elevated BMAL1 mRNA was an inde-pendent protective factor[HR(95％CI)=0.314(0.172-0.572)].The AUC values for predicting poor prognosis in sepsis-asso-ciated AKI patients using serum CITED2,BMAL1 mRNA,NSUN3 mRNA individually and in combination were 0.794,0.814,0.810,and 0.916,respectively.The combined assessment demonstrated superior predictive value compared to individual markers(Z=2.780,2.084,2.435;P=0.005,0.037,0.015).Conclusion Patients with sepsis-associated AKI exhibit elevated serum levels of CITED2 and NSUN3 alongside decreased BMAL1 levels.These three markers correlate with disease severity and poor prognosis,potentially serving as biomarkers for predicting 28-day mortality in patients with sepsis-associated AKI.