危重症患者脓毒症急性肾损伤后的早期恢复模式与预后

Early recovery status and outcomes after sepsis-associated acute kidney injury in critically ill patients

目的:急性肾损伤(acute kidney injury,AKI)是脓毒症的危重症患者常见的并发症之一,可增加患者死亡、心血管事件和慢性肾功能不全的发生风险。AKI持续时间和AKI后肾功能恢复状况可影响患者的预后,但是脓毒症AKI后患者的早期恢复情况是否与预后密切相关,目前仍存在争议。早期预测AKI后肾功能恢复状态有利于制订个体化的治疗策略和预防严重并发症的发生,然而如何在临床上早期识别脓毒症AKI患者中肾功能未恢复的高危患者尚不清楚。本研究旨在探讨危重症患者脓毒症AKI后早期恢复状态与预后的关系,并早期识别肾功能未恢复的危险因素,以提高患者的生存质量。方法:回顾性分析2015年1月至2017年3月在中南大学湘雅二医院和湘雅三医院重症监护室(intensive care unit,ICU)住院且在进入ICU后48 h内发生AKI的脓毒症患者的临床资料。脓毒症的诊断根据第3版脓毒症与感染性休克定义国际共识(the Third International Consensus Definitions for Sepsis and Septic Shock,Sepsis-3),AKI的诊断和分期根据2012年改善全球肾脏病预后组织(Kidney Disease:Improving Global Outcomes,KDIGO)指南。根据诊断AKI后第7天的恢复状态,将脓毒症AKI患者分为完全恢复、部分恢复和未恢复3组。收集患者的基线特征,包括人口学特征、合并症、进入ICU时的临床和实验室检查资料以及进入ICU后24 h内的干预情况。研究的主要结局为90 d时死亡和慢性透析的复合结局,次要结局包括ICU停留天数、住院天数和持续性肾功能不全。使用多因素回归分析评估AKI后早期恢复状态对90 d预后的预测价值,并确定AKI后肾功能未恢复的危险因素。此外,我们进一步分别对诊断AKI后第7天仍在院的患者、无慢性肾脏病病史的患者和AKI分期为2~3期的患者进行敏感性分析。结果:在553例脓毒症AKI患者中,完全恢复组为251例(45.4%),部分恢复组为73例(13.2%),未恢复组为229例(41.4%)。与完全恢复组或部分恢复组患者相比,未恢复组患者90 d死亡(未恢复组vs部分恢复组、完全恢复组:64.2%vs 26.0%、22.7%;P<0.001)和复合结局(未恢复组vs部分恢复组、完全恢复组:65.1%vs 27.4%、22.7%;P<0.001)的发生率更高。此外,未恢复组患者与其他两组患者相比,住院时间更短,进展为持续性肾功能不全的比例更高。在校正了混杂因素后,与完全恢复组患者相比,未恢复组患者90 d死亡(HR=3.50,95%CI:2.47~4.96,P<0.001)和复合结局(OR=5.55,95%CI:3.43~8.98,P<0.001)发生的风险明显增加,而部分恢复组患者与完全恢复组比较差异无统计学意义(P>0.05)。男性、充血性心力衰竭、肺炎、呼吸频率>20次/min、贫血、高胆红素血症、需要机械通气和AKI 3期是AKI后肾功能未恢复的独立危险因素。敏感性分析结果进一步支持在特定患者亚组中AKI后肾功能未恢复仍然是90 d死亡和复合结局的独立预测因素。结论:危重症患者脓毒症AKI后早期恢复状态与预后不良密切相关,诊断AKI后7 d内肾功能未恢复是90 d死亡和复合结局的独立预测因素。男性、充血性心力衰竭、肺炎、呼吸增快、贫血、高胆红素血症、呼吸衰竭和严重AKI是AKI后肾功能未恢复的危险因素。因此,对于脓毒症AKI患者,应在早期阶段实时评估肾功能恢复状态,AKI后肾功能未恢复的患者则需要在住院期间持续评估肾功能,出院后加强随访,预防远期不良事件的发生。

Objective:Acute kidney injury(AKI)is one of the common complications in critically ill septic patients,which is associated with increased risks of death,cardiovascular events,and chronic renal dysfunction.The duration of AKI and the renal function recovery status after AKI onset can affect the patient prognosis.Nevertheless,it remains controversial whether early recovery status after AKI is closely related to the prognosis in patients with sepsis associated AKI(SA-AKI).In addition,early prediction of renal function recovery after AKI is beneficial to individualized treatment decision-making and prevention of severe complications,thus improving the prognosis.At present,there is limited clinical information on how to identify SA-AKI patients at high risk of unrecovered renal function at an early stage.The study aims to investigate the association between early recovery status after SA-AKI,identify risk factors for unrecovered renal function,and to improve patients’quality of life.Methods:We retrospectively analyzed clinical data of septic patients who were admitted to the intensive care unit(ICU)and developed AKI within the first 48 hours after ICU admission in the Second Xiangya Hospital and the Third Xiangya Hospital of Central South University from January 2015 to March 2017.Sepsis was defined based on the Third International Consensus Definitions for Sepsis and Septic Shock(Sepsis-3).AKI was diagnosed and staged according to the 2012 Kidney Disease:Improving Global Outcomes(KDIGO)guideline.SA-AKI patients were assigned into 3 groups including a complete recovery group,a partial recovery group,and an unrecovered group based on recovery status at Day 7 after the diagnosis of AKI.Patients’baseline characteristics were collected,including demographics,comorbidities,clinical and laboratory examination information at ICU admission,and treatment within the first 24 hours.The primary outcome of the study was the composite of death and chronic dialysis at 90 days,and secondary outcomes included length of stay in the ICU,length of stay in the hospital,and persistent renal dysfunction.Multivariate regression analysis was performed to evaluate the prognostic value of early recovery status after AKI and to determine the risk factors for unrecovered renal function after AKI.Sensitivity analysis was conducted in patients who still stayed in hospital on Day 7 after AKI diagnosis,patients without premorbid chronic kidney disease,and patients with AKI Stage 2 to 3.Results:A total of 553 SA-AKI patients were enrolled,of whom 251(45.4%),73(13.2%),and 229(41.4%)were categorized as the complete recovery group,the partial recovery group,and the unrecovered group,respectively.Compared with the complete or partial recovery group,the unrecovered group had a higher incidence of 90-day mortality(unrecovered vs partial recovery or complete recovery:64.2%vs 26.0%or 22.7%;P<0.001)and 90-day composite outcome(unrecovered vs partial recovery or complete recovery:65.1%vs 27.4%or 22.7%;P<0.001).The unrecovered group also had a shorter length of stay in the hospital and a larger proportion of progression into persistent renal dysfunction than the other 2 groups.After adjustment for potential confounders,patients in the unrecovered group were at an increased risk of 90-day mortality(HR=3.50,95%CI 2.47 to 4.96,P<0.001)and 90-day composite outcome(OR=5.55,95%CI 3.43 to 8.98,P<0.001)when compared with patients in the complete recovery group,but patients in the partial recovery group had no significant difference(P>0.05).Male sex,congestive heart failure,pneumonia,respiratory rate>20 beats per minute,anemia,hyperbilirubinemia,need for mechanical ventilation,and AKI Stage 3 were identified as independent risk factors for unrecovered renal function after AKI.The sensitivity analysis further supported that unrecovered renal function after AKI remained an independent predictor for 90-day mortality and composite outcome in the subgroups.Conclusion:The early recovery status after AKI is closely associated with poor prognosis in critically ill patients with SA-AKI.Unrecovered renal function within the first 7 days after AKI diagnosis is an independent predictor for 90-day mortality and composite outcome.Male sex,congestive heart failure,pneumonia,tachypnea,anemia,hyperbilirubinemia,respiratory failure,and severe AKI are risk factors for unrecovered renal function after AKI.Therefore,timely assessment for the renal function in the early phase after AKI diagnosis is essential for SA-AKI patients.Furthermore,patients with unrecovered renal function after AKI need additional management in the hospital,including rigorous monitoring,avoidance of nephrotoxin,and continuous assessment for the renal function,and after discharge,including more frequent follow-up,regular outpatient consultation,and prevention of long-term adverse events.