Relationship between serum lncRNA CRNDE and SIRT1 mRNA levels and stage of acute kidney injury and prognosis within 28 days in patients with sepsis acute kidney injury

Ma Li; Wang Chengli; Li Gang; He Mingsen

doi:10.3969/j.issn.1671-6450.2025.07.005

Abstract：Objective To investigate the relationship between serum long non coding RNA colorectal neoplasia dif-ferentially expressed gene(lncRNA CRNDE)and silencing information regulator 1(SIRT1)levels and the stage of AKI and prognosis within 28 days in patients with sepsis acute kidney injury(AKI).Methods From February 2021 to July 2024,102 patients with sepsis AKI admitted to the Department of Critical Care Medicine,3201 Hospital Affiliated to Xi'an Jiaotong University School of Medicine were selected as the sepsis AKI group,93 patients with simple sepsis as the sepsis group,an-other 102 patients who underwent health checkups in hospitals during the same period were selected as the healthy control group.According to the AKI staging criteria,the patients with sepsis AKI group were divided into:23 cases AKI stage Ⅰ,43 cases AKI stage Ⅱ and 36 cases AKI stage Ⅲ.According to the 28-day survival of patients with sepsis AKI,they were divid-ed into survival subgroup 81 cases(survived within 28 days)and death subgroup 21 cases(died within 28 days).The clinical data of the subjects at admission were collected and the serum kidney injury indicators[cystatin C(Cys-C),creatinine(SCr),blood urea nitrogen(BUN),neutrophil-gelatinase-associated lipid carrier protein(NGAL),kidney injury molecule-1(KIM-1)]were detected.Acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score and sequential organ failure assessment(SOFA)score at admission were performed in sepsis AKI group and sepsis group.Serum lncRNA CRNDE and SIRT1 levels were detected by fluorescence quantitative PCR and enzyme-linked immunosorbent assay,respectively.The correlation of ser-um lncRNA CRNDE and SIRT1 levels with APACHE Ⅱ score,SOFA score and kidney injury indicators in patients with sep-sis AKI was analyzed by Pearson method.Cox regression analysis was performed to analyze the influencing factors of death within 28 days in patients with sepsis AKI.Receiver operating characteristic(ROC)curve was used to evaluate the value of serum lncRNA CRNDE and SIRT1 levels in predicting death within 28 days in patients with sepsis AKI.Results Compared with healthy control group,heart rate and Cys-C in sepsis group were significantly increased(t/P=15.929/＜0.001,9.070/＜0.001),and heart rate,Cys-C,SCr,BUN,NGAL and KIM-1 in sepsis AKI group were significantly increased(t/P=16.577/＜0.001,58.367/＜0.001,74.060/＜0.001,31.215/＜0.001,37.756/＜0.001,30.060/＜0.001);compared with sepsis group,APACHE Ⅱ score,SOFA score,Cys-C,SCr,BUN,NGAL and KIM-1 in sepsis AKI group were significantly increased(t/P=14.009/＜0.001,14.997/＜0.001,54.223/＜0.001,68.920/＜0.001,29.031/＜0.001,34.946/＜0.001,28.389/＜0.001).Serum ln-cRNA CRNDE levels in healthy control group,sepsis group and sepsis AKI group were increased successively,and serum SIRT1 levels were decreased successively(F/P=2 222.437/＜0.001,257.866/＜0.001).Serum lncRNA CRNDE levels in patients with AKI stage Ⅰ,AKI stage Ⅱ and AKI stage Ⅲ were increased successively,while SIRT1 levels were decreased successively(F/P=126.602/＜0.001,117.367/＜0.001).Serum lncRNA CRNDE levels in patients with sepsis AKI was negatively correlated with SIRT1(r/P=-0.605/＜0.001),and positively correlated with APACHE Ⅱ score,SOFA score,Cys-C,SCr,BUN,NGAL and KIM-1(r/P=0.542/＜0.001,0.503/＜0.001,0.489/＜0.001,0.471/＜0.001,0.425/＜0.001,0.413/＜0.001,0.538/＜0.001);serum SIRT1 levels was negatively correlated with APACHE Ⅱ score,SOFA score,Cys-C,SCr,BUN,NGAL and KIM-1(r/P=-0.526/＜0.001,-0.514/＜0.001,-0.505/＜0.001,-0.493/＜0.001,-0.481/＜0.001,-0.429/＜0.001,-0.519/＜0.001).Compared with survival subgroup,APACHE Ⅱ score,SOFA score,Cys-C,SCr,BUN,NGAL,KIM-1 and lncRNA CRNDE in death subgroup were significantly increased,while SIRT1 was significantly decreased(t/P=7.356/＜0.001,12.000/＜0.001,33.798/＜0.001,7.028/＜0.001,8.183/＜0.001,5.065/＜0.001,8.820/＜0.001,19.668/＜0.001,10.988/＜0.001).High APACHE Ⅱscore,high SOFA score,high Cys-C,high SCr,high BUN,high NGAL,high KIM-1 and high lncRNA CRNDE were all inde-pendent risk factors for death within 28 days in patients with sepsis AKI,and high SIRT1 was independent protective factor[OR(95％CI)=1.998(1.147-3.479),1.868(1.142-3.056),2.016(1.115-3.643),1.685(1.143-2.485),1.960(1.208-3.181),2.237(1.176-4.254),2.113(1.209-3.694),2.601(1.336-5.065),0.442(0.279-0.700)].The area under curve(AUC)of serum lncRNA CRNDE,SIRT1 and their combination in predicting death within 28 days in patients with sepsis AKI were 0.787,0.816 and 0.905,respectively,the AUC predicted by the combination of the two was significantly higher than that predicted by lncRNA CRNDE and SIRT1 alone(Z=1.758,1.431,all P＜0.001).Conclusion Serum lncRNA CRNDE expression was high and SIRT1 expression was low in patients with sepsis AKI,both of which were correlated with the stage of AKI,kidney injury indicators and prognosis within 28 days,and could help predict death within 28 days.