■脓毒症患者的预后预测具有挑战性,目前依赖于许多参数的连续测量。标准诊断工具,如血清肌酐(SCr),对急性肾损伤(AKI)缺乏敏感性和特异性。循环无细胞DNA(cfDNA),可以从液体活检中获得,可能有助于量化组织损伤和预测脓毒症死亡率和脓毒症相关AKI(SA-AKI)。
■我们研究了cfDNA水平作为28天死亡率预测指标的临床意义,脓毒症患者SA-AKI的发生和肾脏替代治疗(RRT)的开始。此外,我们调查了脓毒症幸存者在脓毒症发病后6个月和12个月时cfDNA水平的长期过程.具体来说,我们测量了线粒体DNA(线粒体编码的NADH-泛醌氧化还原酶链1,mt-ND1和线粒体编码的细胞色素C氧化酶亚基III,mt-CO3)和核DNA(核核糖体蛋白S18,n-Rps18)在81个健康对照和在3±1天获得的150名重症监护病房败血症患者的所有可用样本中,7±1天,败血症发病后6±2个月和12±2个月。
■我们的分析表明,在第3天,脓毒症患者的cfDNA(mt-ND1和n-Rps18,均p<0.001)水平升高,在脓毒症急性期后降低.与28天幸存者(84%)相比,28天非败血症幸存者(16%)的cfDNA水平更高(所有p<0.05)。与没有AKI的患者相比,具有SA-AKI的患者具有更高水平的cfDNA(所有p<0.05)。在需要RRT的患者中,无细胞DNA也显著增加(所有p<0.05)。所有参数都提高了SCr预测RRT的AUC(AUC=0.88)以及APACHEII预测死亡率(AUC=0.86)。
■总之,cfDNA可能会改善死亡率的风险预测模型,脓毒症患者的SA-AKI和RRT。cfDNA的预测价值,即使在脓毒症发作时进行一次测量,与需要重复测量或基线值进行风险评估的常规诊断方法相比,可以提供显着的优势。考虑到我们的数据显示cfDNA水平在第一次侮辱后下降,未来的研究可以将cfDNA作为“无记忆”标记进行研究,从而为SA-AKI诊断的复杂领域带来进一步的创新.
UNASSIGNED: Outcome-prediction in patients with sepsis is challenging and currently relies on the serial measurement of many parameters. Standard diagnostic tools, such as serum creatinine (SCr), lack sensitivity and specificity for acute kidney injury (AKI). Circulating cell-free DNA (cfDNA), which can be obtained from liquid biopsies, can potentially contribute to the quantification of tissue damage and the prediction of sepsis mortality and sepsis-associated AKI (SA-AKI).
UNASSIGNED: We investigated the clinical significance of cfDNA levels as a predictor of 28-day mortality, the occurrence of SA-AKI and the initiation of renal replacement therapy (RRT) in patients with sepsis. Furthermore, we investigated the long-term course of cfDNA levels in sepsis survivors at 6 and 12 months after sepsis onset. Specifically, we measured mitochondrial DNA (mitochondrially encoded NADH-ubiquinone oxidoreductase chain 1, mt-ND1, and mitochondrially encoded cytochrome C oxidase subunit III, mt-CO3) and nuclear DNA (nuclear ribosomal protein S18, n-Rps18) in 81 healthy controls and all available samples of 150 intensive care unit patients with sepsis obtained at 3 ± 1 days, 7 ± 1 days, 6 ± 2 months and 12 ± 2 months after sepsis onset.
UNASSIGNED: Our analysis revealed that, at day 3, patients with sepsis had elevated levels of cfDNA (mt-ND1, and n-Rps18, all p<0.001) which decreased after the acute phase of sepsis. 28-day non-survivors of sepsis (16%) had higher levels of cfDNA (all p<0.05) compared with 28-day survivors (84%). Patients with SA-AKI had higher levels of cfDNA compared to patients without AKI (all p<0.05). Cell-free DNA was also significantly increased in patients requiring RRT (all p<0.05). All parameters improved the AUC for SCr in predicting RRT (AUC=0.88) as well as APACHE II in predicting mortality (AUC=0.86).
UNASSIGNED: In summary, cfDNA could potentially improve risk prediction models for mortality, SA-AKI and RRT in patients with sepsis. The predictive value of cfDNA, even with a single measurement at the onset of sepsis, could offer a significant advantage over conventional diagnostic methods that require repeated measurements or a baseline value for risk assessment. Considering that our data show that cfDNA levels decrease after the first insult, future studies could investigate cfDNA as a \"memoryless\" marker and thus bring further innovation to the complex field of SA-AKI diagnostics.