A pulmonary source of infection in patients with sepsis-associated acute kidney injury leads to a worse outcome and poor recovery of kidney function

BACKGROUND:Hospital mortality rates are higher among patients with sepsis-associated acute kidney injury(SA-AKI)than among patients with sepsis.However,the pathogenesis underlying SA-AKI remains unclear.We hypothesized that the source of infection affects development of SA-AKI.We aim to explore the relationship between the anatomical source of infection and outcome in patients with SA-AKI.METHODS:Between January 2013 and January 2018,113 patients with SA-AKI admitted to our Emergency Center were identifi ed and divided into two groups:those with pulmonary infections and those with other sources of infection.For each patient,we collected data from admission until either discharge or death.We also recorded the clinical outcome after 90 days for the discharged patients.RESULTS:The most common source of infection was the lung(52/113 cases,46%),followed by gastrointestinal(GI)(25/113 cases,22.1%)and urinary(22/113,19.5%)sources.Our analysis showed that patients with SA-AKI had a significantly worse outcome(30/52 cases,P<0.001)and poorer kidney recovery(P=0.015)with pulmonary sources of infection than those infected by another source.Data also showed that patients not infected by a pulmonary source more likely experienced shock(28/61 cases,P=0.037).CONCLUSION:This study demonstrated that the source of infection infl uenced the outcome of SA-AKI patients in an independent manner.Lung injury may influence renal function in an asyet undetermined manner as the recovery of kidney function was poorer in SA-AKI patients with a pulmonary source of infection.

Eff ects of continuous renal replacement therapy on infl ammation-related anemia, iron metabolism and prognosis in sepsis patients with acute kidney injury

BACKGROUND:This study aims to evaluate the eff ect of continuous renal replacement therapy(CRRT)on inflammation-related anemia,iron metabolism,and the prognosis in sepsis patients with acute kidney injury(AKI).METHODS:Sepsis patients with AKI were prospectively enrolled and randomized into the CRRT and control groups.The clinical and laboratory data on days 1,3 and 7 after intensive care unit(ICU)admission were collected.The serum interleukin(IL)-6,hepcidin,erythropoietin,ferritin,and soluble transferrin receptor(sTfR)were determined by enzyme-linked immunosorbent assay.The Sequential Organ Failure Assessment(SOFA)score and 28-day mortality were recorded.Data were analyzed using Pearson’s Chi-square test or Fisher’s exact test(categorical variables),and Mann-Whitney U-test or t-test(continuous variables).RESULTS:The hemoglobin and serum erythropoietin levels did not signifi cantly diff er between the CRRT and control groups though gradually decreased within the first week of ICU admission.On days 3 and 7,the serum IL-6,hepcidin,ferritin,and red blood cell distribution width significantly decreased in the CRRT group compared to the control group(all P<0.05).On day 7,the serum iron was significantly elevated in the CRRT group compared to the control group(P<0.05).However,the serum sTfR did not signifi cantly diff er between the groups over time.In addition,the SOFA scores were signifi cantly lower in the CRRT group compared to the control group on day 7.The 28-day mortality did not signifi cantly diff er between the control and CRRT groups(38.0%vs.28.2%,P=0.332).CONCLUSION:CRRT might have beneficial effects on the improvement in inflammationrelated iron metabolism and disease severity during the fi rst week of ICU admission but not anemia and 28-day mortality in sepsis patients with AKI.

Effect of continuous low effective dialysis combined with hemoperfusion on inflammatory stress, hemodynamic parameters and renal function in septic patients with severe acute kidney injury

Objective:To investigate the effects of sustained low-efficiency dialysis (SLED) combined with hemoperfusion (HP) on inflammatory stress, hemodynamic parameters and renal function in septic patients with severe acute kidney injury.Methods: A total of 82 cases of sepsis with severe acute renal injury were divided into control group (n=41) and observation group (n=41) according to the random data table method. Two groups of patients were given conventional support treatment, on this basis, the control group was treated with Continuous renal replacement therapy (CRRT), and the observation group was treated with SLED plus HP. The levels of inflammatory factors, hemorheological parameters and renal function indexes of the two groups were compared before and after treatment.Results: There was no significant difference in the levels of CRP, WBC, PCT, MAP, OI, BUN and Scr between the control group and the observation group before the treatment. Compared with the level before treatment, the levels of CRP, WBC, PCT, BUN and Scr in the two groups were significantly decreased after treatment, while the levels of MAP and OI were significantly increased. Compared with the level of the control group after treatment, the levels of CRP, WBC, PCT, BUN and Scr in the observation group were significantly lower than those in the control group, the levels of MAP and OI were significantly increased, the difference was statistically significant.Conclusion:SLED combined with HP regimen in treatment of sepsis combined with severe acute kidney injury can effectively inhibit the release of inflammatory factors, improve hemodynamics and renal function, and has an important clinical value.

Timing of Continuous Renal Replacement Therapy Initiation in Sepsis-Associated Acute Kidney Injury: A Comprehensive Review and Future Directions

This review examines the application of continuous renal replacement therapy(CRRT)in patients with sepsis-associated acute kidney injury(S-AKI),with a particular focus on the timing of CRRT initiation.This review addresses the controversy surrounding initiation timing and proposes future research directions.Through a systematic review of recent literature on CRRT for S-AKI,working principles,therapeutic mechanisms,initiation timing of CRRT,and related meta-analyses were summarized.Current studies indicate that the optimal timing for CRRT initiation in S-AKI patients remains inconclusive,with ongoing debate regarding whether early initiation significantly improves patient survival and renal function.This lack of consensus reflects the heterogeneity of the S-AKI patient population and the limitations of existing research methodologies.Future studies should focus on advancing the application of precision medicine in S-AKI and developing individualized treatment strategies by integrating multidimensional information to optimize CRRT utilization and improve patient outcomes.

Efficacy of Ulinastatin Combined with Continuous Renal Replacement Therapy in the Treatment of Sepsis Acute Kidney Injury and Its Effects on Systemic Inflammation, Immune Function and miRAN Expression

Objective: To research the effectiveness of ulinastatin in combination with continuous renal replacement therapy in treating sepsis acute kidney injury and its effect on systemic inflammation, immune function and miRAN expression. Methods: The 84 patients who were diagnosed with sepsis complicated by acute kidney injury in our hospital between May 2020 and June 2022 were chosen and randomly assigned to the study group (n = 42) and the control group (n = 42). Ulinastatin in combination with continuous renal replacement therapy was administered to the study group, whereas the control group was administered with continuous renal replacement therapy alone. Both groups’ clinical effects were observed. The levels of blood urea nitrogen (BUN), serum creatinine (SCr), tumor necrosis factor-α (TNF-α), high sensitivity Creactive protein (hs-CRP), vascular cell adhesion molecule-1 (VCAM-1), IgG, IgA, IgM, expression levels of miR-233 and miR-10a were compared among both the groups, pre-, and post-treatment. Results: The study group’s overall effectiveness rate was higher that is 95.24%, in comparison to the control group’s 78.57%, and this difference was statistically significant (P α, hs-CRP, VCAM-1, and miR-233 and miR-10a expression levels in both the study and control groups were decreased, however, the study group had reduced levels in comparison to the control group, with statistically significant differences (P P Conclusion: Ulinastatin in combination with continuous renal replacement therapy for treating sepsis acute kidney injury exhibits a positive effect and can significantly improve the systemic inflammation and immune function in patients.

Changing picture of renal cortical necrosis in acute kidney injury in developing country

Renal cortical necrosis(RCN) is characterized by patchy or diffuse ischemic destruction of all the elements of renal cortex resulting from significantly diminished renal arterial perfusion due to vascular spasm and microvascular injury. In addition, direct endothelial injury particularly in setting of sepsis, eclampsia, haemolytic uremic syndrome(HUS) and snake bite may lead to endovascular thrombosis with subsequent renal ischemia. Progression to end stage renal disease is a rule in diffuse cortical necrosis. It is a rare cause of acute kidney injury(AKI) in developed countries with frequency of 1.9%-2% of all patients with AKI. In contrast, RCN incidence is higher in developing countries ranging between 6%-7% of all causes of AKI. Obstetric complications(septic abortion, puerperal sepsis, abruptio placentae, postpartum haemorrhage and eclampsia) are the main(60%-70%) causes of RCN in developing countries. The remaining 30%-40% cases of RCN are caused by non-obstetrical causes, mostly due to sepsis and HUS. The incidence of RCN ranges from 10% to 30% of all cases of obstetric AKI compared with only 5% in non-gravid patients. In the developed countries, RCN accounts for 2% of all cases of AKI in adults and more than 20% of AKI during the third trimester of pregnancy. The reported incidence of RCN in obstetrical AKI varies between 18%-42.8% in different Indian studies. However, the overall incidence of RCN in pregnancy related AKI has decreased from 20%-30% to 5% in the past two decades in India. Currently RCN accounts for 3% of all causes of AKI. The incidence of RCN in obstetrical AKI was 1.44% in our recent study. HUS is most common cause of RCN in non-obstetrical group, while puerperal sepsis is leading cause of RCN in obstetric group. Because of the catastrophic sequelae of RCN, its prevention and aggressive management should always be important for the better renal outcome and prognosis of the patients.

Early initiation renal replacement therapy for fluid management to reduce central venous pressure is more conducive to renal function recovery in patients with acute kidney injury

Background:Acute kidney injury (AKI) is a serious complication in critically ill patients with septic shock treated in the intensive care unit. Renal replacement therapy (RRT) is a treatment for severe AKI;however, the time of initiation of RRT and factors that affect the recovery of kidney function remains unclear. This study was to explore whether early initiation of RRT treatment for fluid management to reduce central venous pressure (CVP) can help to improve patients5 kidney function recovery. Methods: A retrospective analysis of septic patients who had received RRT treatment was conducted. Patients received RRT either within 12 h after they met the diagnostic criteria of renal failure (early initiation) or after a delay of 48 h if renal recovery had not occurred (delayed initiation). Parameters such as patients5 renal function recovery at discharge, fluid balance, and levels of CVP were assessed. Results: A total of 141 patients were eligible for enrolment: 40.4% of the patients were in the early initiation group (57 of 141 patients), and 59.6% were in the delayed initiation group (84 of 141 patients). There were no significant differences in the characteristics at baseline between the two groups, and there were no differences in 28-day mortality between the two groups (χ^2 = 2.142, P = 0.143);however, there was a significant difference in the recovery rate of renal function between the two groups at discharge (χ^2 = 4.730, P < 0.001). More importantly, early initiation of RRT treatment and dehydration to reduce CVP are more conducive to the recovery of renal function in patients with AKI. Conclusion: Compared with those who received delayed initiation RRT, patients who received early-initiation RRT for dehydration to reduce CVP have enhanced kidney function recovery.

Risk factors of acute renal injury in patients with acute left heart failure

Objective To investigate the risk factors of acute renal injury(acute kidney injury)in patients with acute left heart failure.Methods Clinical data of 188 patients with acute left heart failure who were admitted to our hospital were retrospectively analyzed.Logistic regression analysis was used to assess the risk factors for AKI.

丹红注射液联合肝素治疗脓毒症并发急性肾损伤的效果

目的探讨丹红注射液联合肝素治疗脓毒症并发急性肾损伤的临床疗效及对血清高迁移率族蛋白B1(high mobility group box 1,HMGB1)和可溶性髓样细胞触发受体-1(soluble triggering receptor expressed on myeloid cells-1,sTREM-1)水平的影响。方法选取收治的80例脓毒症并发急性肾损伤患者作为研究对象,用随机数字表法分为2组,每组40例,2组均予以常规治疗,对照组加用低分子肝素,观察组加用低分子肝素和丹红注射液。对比2组的治疗效果,记录2组治疗前后的血清HMGB1、sTREM-1、肾功能指标及凝血功能指标等的变化。结果与治疗前比较,2组治疗后的各项生命指标、炎症指标、凝血功能指标、肾功能指标、HMGB1及sTREM-1水平均得到明显改善(P<0.05)。与对照组比较,观察组治疗后的体温、心率及急性生理学及慢性健康状况评分系统Ⅱ(acute physiology and chronic health evaluationⅡ,APACHEⅡ)评分均明显更低,血清白细胞介素-6(interleutin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、C反应蛋白(C-reactive protein,CRP)、降钙素原(procall⁃citonin,PCT)、血肌酐(screatinine,Scr)、胱抑素C(cystatin C,CysC)、尿素氮(blood urea nitrogen,BUN)、纤维蛋白原(fibrinogen,FIB)及D-二聚体(D-dimer,D-D)的水平均更低,机械通气时间及ICU住院时间明显更短,凝血酶原时间(prothrombin time,PT)明显更长(P<0.05)。2组治疗后的存活率比较差异无统计学意义(P>0.05)。结论丹红注射液联合肝素治疗能够通过抑制sTREM-1、HMGB1的表达,减轻炎症反应,改善凝血功能,增大肾灌注,减轻肾组织损伤,从而治疗脓毒症并发急性肾损伤。

不同中心静脉压水平在脓毒症相关性急性肾损伤中的作用

目的探讨中心静脉压(central venous pressure,CVP)水平在脓毒症相关性急性肾损伤(sepsis-associated acute kidney injury,SA-AKI)发生和发展过程中的作用。方法应用盲肠结扎穿孔(cecal ligation and puncture,CLP)法诱导雄性SD大鼠脓毒症模型24h,以假手术组作为对照,给予两组大鼠静脉注射乳酸钠林格注射液诱导CVP升高至10、15和20mmHg,动态监测大鼠平均动脉压(mean arterial pressure,MAP)、心率(heart rate,HR)和动脉血乳酸(lactate,Lac),应用测流暗场成像(side stream darkfield imaging,SDF)技术检测大鼠肾脏皮质微循环灌注血管密度(perfused small vessel density,PVD)和微血管流动指数(microvascular flow index,MFI),并检测血肌酐(creatinine,CRE)、尿中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase associated lipocalin,NGAL)和肾组织白细胞介素6(interleukin-6,IL-6)水平和肾脏病理变化。结果与假手术组比较,CLP大鼠的MAP显著下降、HR和Lac显著升高(P<0.05);肾脏PVD和MFI显著下降(P<0.05),血CRE、尿NGAL和肾脏IL-6显著升高(P<0.05)。与CVP 10mmHg比较,CLP大鼠在CVP 20mmHg时的PVD和MFI显著降低(P<0.05);假手术组大鼠在CVP 15mmHg和20mmHg时的PVD和MFI显著低于CVP 10mmHg(P<0.05)。CLP大鼠在CVP 15mmHg时的IL-6显著高于CVP 10mmHg(P<0.05),CVP 20mmHg时的IL-6显著高于CVP 15mmHg(P<0.05)。CLP大鼠随CVP逐渐升高而表现为皮质和髓质水肿,肾小管上皮细胞空泡变性、刷状缘脱落、肾小管阻塞、Bowman囊间隙消失,且髓质水肿较皮质明显。假手术组大鼠在CVP达20mmHg时,肾小球、肾小管肿胀,Bowman囊间隙变窄。结论过高的CVP水平可以降低CLP大鼠肾脏皮质微循环灌注、促进局部炎性细胞因子活化和肾组织水肿,在SA-AKI过程中发挥损伤作用。

床旁超声造影定量评价脓毒症早期急性肾损伤的肾脏微循环灌注

目的:探讨床旁超声造影技术(CEUS)对脓毒症早期急性肾损伤(AKI)患者肾脏微血管灌注变化的动态评价和临床应用价值。方法:纳入本院重症监护室收治的脓毒症患者45例,依据诊断标准分为早期AKI组(S-EAKI组,n=25)和无AKI组(S-NAKI组,n=20)。记录患者基本临床资料和生化指标检查结果,于入院当日(第0天)和第3天行床旁肾脏CEUS检查,测量肾脏大小、实质厚度、肾段动脉阻力指数(RI)、肾皮质及髓质的CEUS定量参数:达峰时间(TTP)、峰值强度(PI)及曲线下面积(AUC)。以同期在院行CEUS的无泌尿系统疾病患者为对照组(n=20),对比观察上述指标的差异。结果:肾脏常规超声结果显示,与对照组相比,脓毒症患者肾脏大小、实质厚度及RI无统计学差异;但CEUS显示S-EAKI组及S-NAKI组皮质PI、AUC与髓质AUC均显著降低(P<0.01)、皮髓质TTP显著延长(P<0.01),且S-EAKI组较S-NAKI组变化明显(P<0.01)。受试者工作特征(ROC)曲线分析皮质TTP、PI、AUC及髓质TTP预测脓毒症早期AKI的曲线下面积分别为0.71、0.78、0.75、0.74(P<0.01)。随病程时间变化,与第0天比较,S-EAKI组在第3天时皮髓质AUC降低(P<0.05),S-NAKI组造影参数显示灌注改善(P<0.05)。结论:床旁CEUS能在重症监护室有效评估脓毒症早期AKI的肾脏微循环灌注状况。

脓毒症合并急性肾损伤患者行持续性肾脏替代治疗时机的探讨

目的探讨脓毒症合并急性肾损伤(AKI)患者行持续性肾脏替代治疗(CRRT)的最佳治疗时机。方法我院收治的86例脓毒症合并AKI患者,其中44例行早期CRRT治疗(早期组),42例行标准CRRT治疗(标准组),记录两组预后转归情况及入院时、入院24、48及72 h肾损伤标志物[肾损伤分子-1(KIM-1)、中性粒细胞明胶酶脂质运载蛋白(NGAL)、肝型脂肪酸结合蛋白(L-FABP)]变化情况;根据标准组入院28 d生存情况分为生存组及死亡组,比较两组CRRT治疗时机、入院24 h肾损伤标志物差异,分析入院24 h肾损伤标志物对标准CRRT治疗预后死亡的预测价值。结果早期组与标准组入院28 d死亡率比较,差异无统计学意义(P>0.05);早期组入院至行CRRT时间、CRRT持续时间、ICU住院时间及依赖透析率均低于标准组,脱离透析率高于标准组(P<0.05)。从入院时至入院72 h,早期组血清KIM-1、NGAL、L-FABP水平先升高后下降,标准组则升高后稳定(P<0.05);入院48、72 h时早期组血清KIM-1、NGAL、L-FABP水平均低于标准组(P<0.05)。行标准CRRT治疗患者中,死亡组入院至行CRRT时间及入院24 h血清KIM-1、NGAL、L-FABP水平均显著高于生存组(P<0.05);经ROC曲线分析发现入院24 h血清KIM-1、NGAL、L-FABP水平均对标准CRRT治疗预后死亡有较高预测价值(P<0.05),其截断值分别为2.98 ng/L、23.53 ng/L、20.02μg/ml,且3项联合预测价值最高。结论早期CRRT治疗能使脓毒症合并AKI患者尽早脱离透析,入院24 h血清KIM-1、NGAL、L-FABP水平对预测标准CRRT治疗预后不良有利,有望成为指导CRRT治疗的新指标。

连续性肾脏替代新生儿脓毒血症相关性急性肾损伤的临床研究

目的探讨连续性肾脏替代治疗(CRRT)在新生儿脓毒血症相关性急性肾损伤(AKI)治疗中的应用价值。方法本研究回顾性分析2017年6月至2021年8月泉州市儿童医院新生儿科诊治的脓毒血症相关性AKI新生儿26例,均予以CRRT,观察CRRT治疗持续时间、住院时间,并发症、28 d存活率;治疗前、治疗12 h、24 h、48 h及治疗结束后平均动脉压(MAP)、pH值、氧合指数及乳酸、血肌酐、尿素氮、胱抑素C、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、Toll样受体4(TLR4)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL),采用单因素重复测量方差分析比较治疗后不同时间临床指标的变化。结果26例脓毒血症相关性AKI新生儿均顺利完成连续性肾脏替代,28 d存活率88.46%(23/26)。CRRT治疗持续时间为(73.52±12.65)h、住院时间(10.25±2.32)d。CRRT治疗12 h、24 h、48 h及治疗结束后的MAP、氧合指数、pH值高于治疗前,尿量多于治疗前,而乳酸、血肌酐、尿素氮、胱抑素C、TNF-α、IL-6、TLR4、NGAL均低于治疗前,差异具有统计学意义(P<0.05)。CRRT治疗期间出现低血压4例(15.38%)、低体温3例(11.54%)、导管堵塞3例(11.54%)。7例患儿的7 d新生儿神经行为测定(NBNA)评分<35分,2例出现Vojta异常姿势反射。结论CRRT治疗新生儿脓毒血症相关性AKI具有较为理想的效果,能有效降低炎性因子及纠正水电解质紊乱,避免肾脏进一步损伤,且安全性较好,但存在远期脑损伤风险,临床还需提高关注度。

通腑益气汤缓解脓毒症大鼠急性肾损伤实验研究

目的 观察通腑益气汤对脓毒症大鼠急性肾损伤的保护作用。方法 将40只SD大鼠随机分为假手术组(Sham)、模型组(Model)、通腑益气汤低剂量组(TF-L)、通腑益气汤高剂量组(TF-H),每组10只。Sham进行假手术造模,其余各组大鼠建立脓毒症盲肠结扎穿刺模型。TF-L、TF-H组大鼠术后分别以0.275 g/kg、1.1 g/kg剂量灌胃通腑益气汤,Sham、Model组大鼠灌胃等体积蒸馏水,每8 h给药1次,连续给药3 d。第3天检测各组大鼠尿白蛋白排泄率和肌酐清除率评价肾功能,使用运动功能状态量表(Murine Sepsis Score, MSS)评分从行为学评价病情严重程度。取材后ELISA法测定大鼠血清TNF-α、IL-1α、IL-6、sCD14浓度;HE、PAS和Masson染色观察肾脏组织形态;Western blot法检测肾氧化应激指标MDA、CAT和GSH。结果 (1)肾功能:Model组大鼠尿白蛋白排泄率较Sham组升高,肌酐清除率降低;TF-L、TF-H组大鼠尿白蛋白排泄率较Model组降低,TF-H组肌酐清除率升高,差异均有统计学意义(均P<0.05)。(2)血清炎症因子:Model组大鼠血清TNF-α、IL-1α、IL-6、sCD14水平较对照组均升高,TF-H组大鼠血清TNF-α、IL-1α、IL-6、sCD14水平较Model组均降低,TF-L组TNF-α、IL-1α、sCD14水平降低,差异均有统计学意义(均P<0.05)。(3)MSS评分:Model组大鼠各项评分较Sham组升高,TF-H组大鼠除睁眼反应外,其余各项评分均较Model组降低,TF-L组大鼠对刺激反应、呼吸频率2项评分降低,差异均有统计学意义(均P<0.05)。(4)肾组织形态:Model组大鼠肾小管管腔扩张,上皮细胞变性,间质存在明显的胶原纤维沉积,肾小球水肿,存在节段性肾小球硬化;而TF-L、TF-H组大鼠均有一定程度的改善。组织学评分、肾小球硬化指数、肾间质纤维化指数结果与之相符。(5)氧化应激:Model组大鼠肾组织MDA表达较Sham组升高,CAT、GSH表达降低;TF-H组大鼠肾组织MDA表达较Model组降低,CAT、GSH表达升高,TF-L组MDA表达降低,差异均有统计学意义(均P<0.05)。结论 腑益气汤可通过抗氧化应激作用改善脓毒症大鼠的急性肾损伤和整体状况,下调血清炎症因子的表达水平。

血清miR-146a、Lp-PLA2与脓毒症急性肾损伤患者肾功能的相关性分析

目的探讨血清微小RNA-146a(miR-146a)、脂蛋白相关性磷脂酶A2(Lp-PLA2)与脓毒症急性肾损伤(AKI)患者肾功能的相关性。方法选取2020年2月—2022年2月本院感染性疾病科住院的88例脓毒症患者进行回顾性分析,根据入院24 h内是否发生AKI分组(包括入院时已发生AKI的患者),将40例发生AKI的患者设为观察组1,48例未发生AKI的患者设为观察组2,另选取同期本院体检中心的45例健康体检者设为对照组。检测、比较3组入院24 h内/体检时血清miR-146a、Lp-PLA2、肾功能[胱抑素C(Cys-C),血肌酐(Scr)]指标。根据脓毒症AKI疾病严重程度,将观察组1患者分为休克组(7例)、重度组(20例)、轻度组(13例),比较脓毒症AKI患者中不同疾病严重程度、不同AKI分期组血清miR-146a、Lp-PLA2、肾功能指标,Pearson分析miR-146a、Lp-PLA2与肾功能指标的相关性,绘制受试者工作曲线(ROC),计算曲线下面积(AUC),分析miR-146a、Lp-PLA2、肾功能对脓毒症发生AKI的预测效能。结果观察组1入院24 h内血清miR-146a、Lp-PLA2、Cys-C、Scr均高于观察组2及对照组(P<0.05)。脓毒症休克组血清miR-146a、Lp-PLA2、Cys-C、Scr均高于重度组及轻度组(P<0.05)。AKIⅢ期组血清miR-146a、Lp-PLA2、Cys-C、Scr均高于Ⅱ期组及Ⅰ期组(P<0.05)。入院24 h内血清miR-146a、Lp-PLA2与Cys-C、Scr均呈正相关性(P<0.05)(r=0.421、0.417、0.398、0.387)。血清miR-146a、Lp-PLA2、Cys-C、Scr联合检测预测脓毒症发生AKI的AUC为0.798,(95%CI:0.716~0.947),灵敏度是93.13%,特异度是91.84%,联合检测预测脓毒症发生AKI的灵敏度及特异度均高于单独检测(P<0.05)。结论脓毒症AKI患者血清miR-146a、Lp-PLA2呈高表达,与Cys-C、Scr呈相关性,血清miR-146a、Lp-PLA2联合Cys-C、Scr检测可提高对AKI的预测灵敏度及特异度,在脓毒症患者AKI诊断中具有一定的参考价值。

血清TXNIP、NRP1水平对脓毒症患者发生急性肾损伤的预测价值

目的:探讨硫氧还蛋白互作蛋白(TXNIP)、神经纤毛蛋白-1(NRP1)对脓毒症患者发生急性肾损伤(AKI)的预测价值。方法:选取2019年4月-2021年4月在本院住院的160例脓毒症患者为研究对象,以患者7 d内是否发生AKI将患者分为AKI组56例和非AKI组104例,再对AKI患者进行分组,分为AKIⅠ期、AKIⅡ期、AKIⅢ期。酶联免疫吸附法血清TXNIP、NRP1水平;多因素Logistic回归分析脓毒症患者发生AKI的可能影响因素;受试者工作特征(ROC)曲线评估血清TXNIP、NRP1水平检测对脓毒症患者发生AKI的预测价值。结果:AKI组SOFA评分、Scr水平、APACHEⅡ评分及PCT水平均显著高于非AKI组,eGFR水平显著低于非AKI组(P<0.05)。AKI组TXNIP水平显著高于非AKI组,且随AKI分期增加而显著增加(P<0.05);NRP1水平显著低于非AKI组,且随AKI分期增加而显著降低(P<0.05)。AKI患者血清TXNIP水平与SOFA评分、Scr、APACHEⅡ评分均呈正相关(r=0.342、0.361、0.335,P<0.05),与eGFR呈负相关(r=-0.495,P<0.05);血清NRP1水平与SOFA评分、Scr、APACHEⅡ评分均呈负相关(r=-0.310、-0.327、-0.306,P<0.05),与eGFR呈正相关(r=0.561,P<0.05)。Logistic回归分析显示,高水平TXNIP、Scr、SOFA评分是脓毒症患者并发AKI的危险因素(P<0.05),高水平NRP1是脓毒症患者并发AKI的保护因素(P<0.05)。ROC曲线显示,TXNIP、NRP1预测AKI的AUC为0.737、0.720,二者联合预测AKI的AUC为0.929,显著高于二者单独预测(Z_(联合VSTXNIP)=4.642、P=0.004;Z联合VS NRP1=4.929、P=0.025),其敏感度、特异度分别为90.79%、85.29%。结论:脓毒症并发AKI患者血清中TXNIP高表达,NRP1低表达,与AKI严重程度有关,且二者联合对脓毒症并发AKI具有一定的预测价值。

新型抗凝剂甲磺酸萘莫司他在急诊连续性肾脏替代治疗中的临床应用研究

目的研究新型抗凝剂甲磺酸萘莫司他在急诊连续性肾脏替代治疗(CRRT)中的应用价值。方法采用回顾性分析,选取2021年6月至2023年1月入攀钢集团总医院的72例脓毒症伴发AKI患者为研究对象。所有患者均行连续性肾脏替代治疗(CRRT),参考是否接受甲磺酸萘莫司他体外抗凝分为研究组(n=36)与对照组(n=36)。研究组接受甲磺酸萘莫司他体外抗凝,对照组未接受甲磺酸萘莫司他体外抗凝。比较两组患者治疗前、治疗72 h后的实验室指标[国际标准化比值(INR)、活化部分凝血活酶时间(APTT)、血清钠、血清钙、血清钾、尿酸、半胱氨酸蛋白酶抑制剂C(CysC)、尿素氮、血清肌酐、血小板计数、血红蛋白]水平与治疗后滤器使用量、不良反应(过敏反应、高血钾、消化道症状、血小板下降、出血)发生率。结果治疗72 h后,两组患者尿酸、CysC、尿素氮、血清肌酐、血小板计数、血红蛋白水平均明显低于治疗前,研究组患者治疗72 h后尿酸、CysC、尿素氮、血清肌酐水平分别为(86.41±15.24)μmol/L、(0.98±0.19)mg/L、(4.43±2.01)mmol/L、(99.32±15.61)μmol/L,均明显低于对照组[(105.29±20.43)μmol/L、(1.19±0.23)mg/L、(6.92±2.23)mmol/L、(127.54±20.47)μmol/L],差异均有统计学意义(P<0.05)。研究组患者治疗72 h后滤器使用量为(1.29±0.47)个,明显少于对照组[(2.07±0.56)个],差异有统计学意义(P<0.05)。两组患者总不良反应发生率比较,差异无统计学意义(P>0.05)。结论新型抗凝剂甲磺酸萘莫司他在急诊连续性肾脏替代治疗中的效果显著,可有效降低脓毒症伴发AKI患者的滤器更换频率,还可进一步改善其尿酸、CysC、尿素氮、血清肌酐水平,且未增大不良反应发生风险,安全性高。

醒脑静注射液联合乌司他丁、连续性肾脏替代治疗对脓毒症合并急性肾损伤患者的疗效、免疫功能及血流动力学的影响

目的探究醒脑静注射液联合乌司他丁、连续性肾脏替代治疗对脓毒症合并急性肾损伤(acute kidney injury,AKI)患者的疗效、免疫功能及血流动力学的影响。方法选取2019年5月1日至2022年5月31日中国人民解放军联勤保障部队第九八七医院104例脓毒症合并AKI患者,将所有患者按随机数字表法分为观察组(n=52)、对照组(n=52)。对照组采用乌司他丁、连续性肾脏替代治疗,观察组在对照组的基础上联合醒脑静注射液进行治疗。采用急性生理与慢性健康(acute physiology and chronic health evaluation,APACHEⅡ)评分对生理状态进行评定;采用流式细胞仪检测患者治疗前后T淋巴细胞亚群(CD4^(+)、CD8^(+))的水平,并计算CD4^(+)/CD8^(+)的比值;采用单向免疫扩散法测定患者治疗前后的IgA、IgM和IgG水平;采用电子监护仪监测患者治疗前后中心静脉压(central venous pressure,CVP)、平均动脉压(mean arterial pressure,MAP)以及心率(heart rate,HR)。比较两组患者疗效、APACHEⅡ评分、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)、IgA、IgM、IgG、CVP、MAP及HR水平的变化。结果观察组患者疗效显著高于对照组(90.39%比73.08%,χ^(2)=5.216,P=0.022);观察组和对照组的APACHEⅡ评分[(20.57±3.72)分、(19.74±3.51)分比(9.67±2.24)分、(13.84±3.11)分]在治疗后显著降低(P<0.05),治疗后观察组的APACHEⅡ评分显著低于对照组(P<0.05);观察组和对照组的CD4^(+)水平[(30.73±6.54)%、(29.46±6.28)%比(35.82±6.59)%、(32.65±6.74)%]、CD4^(+)/CD8^(+)[(1.10±0.24)、(1.12±0.26)比(1.84±0.31)、(1.52±0.29)]在治疗后均显著增高,CD8^(+)水平[(27.94±5.75)%、(26.30±5.54)%比(19.48±4.21)%、(21.45±4.54)%]显著降低(P<0.05),治疗后观察组的CD4^(+)水平、CD4^(+)/CD8^(+)均显著高于对照组,CD8^(+)水平显著低于对照组(P<0.05);观察组和对照组IgA[(1.32±0.31)g/L、(1.28±0.29)g/L比(1.96±0.48)g/L、(1.63±0.42)g/L]、IgM[(0.95±0.31)g/L、(0.91±0.28)g/L比(1.96±0.51)g/L、(1.37±0.36)g/L]、IgG[(5.82±0.81)g/L、(5.77±0.76)g/L比(9.75±1.43)g/L、(7.32±1.24)g/L]水平在治疗后均显著增高(P<0.05),治疗后观察组IgA、IgM、IgG水平均显著高于对照组(P<0.05);观察组和对照组的CVP[(6.47±1.24)mm H_(2)O、(6.42±1.21)mmH_(2)O比(12.83±2.85)mmH_(2)O、(9.54±2.32)mmH_(2)O]、MAP[(56.53±5.34)mmHg、(55.87±5.21)mmHg比(87.27±6.83)mmHg、(71.92±6.42)mmHg,1 mmHg=0.133 kPa]水平在治疗后均显著增高,HR[(117.56±12.65)次/min、(115.73±12.57)次/min比(83.41±8.73)次/min、(98.65±10.51)次/min]水平显著降低(P<0.05),治疗后观察组的CVP、MAP水平均显著高于对照组,HR水平显著低于对照组(P<0.05)。2组患者尿素氮[(10.38±2.31)mmol/L、(10.42±2.34)mmol/L比(14.22±3.34)mmol/L、(19.14±5.27)mmol/L]、血肌酐[(125.87±26.57)μmol/L、(125.76±25.68)μmol/L比(183.55±36.81)μmol/L、(241.26±42.79)μmol/L]水平在治疗后均显著增高(P<0.05),治疗后观察组的尿素氮、血肌酐水平均显著低于对照组(P<0.05)。结论醒脑静注射液联合乌司他丁、连续性肾脏替代治疗脓毒症合并AKI患者的效果较好,可以有效改善患者的免疫功能和血流动力学,缓解患者病情。

血清FGF-2、FGF-23与脓毒症合并急性肾损伤CRRT治疗患者肾功能及预后的关系

目的 分析血清成纤维细胞生长因子(fibroblast growth factor,FGF)-2、FGF-23与接受连续性肾脏替代治疗(continuous renal replacement therapy,CRRT)的脓毒症合并急性肾损伤(acute kidney injury,AKI)患者肾功能和短期预后的关系。方法 选取157例接受CRRT治疗的脓毒症合并AKI患者,比较不同AKI分期患者血清FGF-2、FGF-23水平。根据28天预后情况将其分为生存组和死亡组,比较2组血清FGF-2、FGF-23及肾功能指标水平,并分析其相关性。分析血清FGF-2、FGF-23水平对短期预后的预测价值。结果 AKIⅢ期患者血清FGF-2水平低于AKIⅡ期,血清FGF-23水平高于AKIⅡ期(t=20.149、-8.060,均P<0.001)。死亡组血清FGF-23、肌酐(Scr)、胱抑素C(Cyc-C)水平高于生存组(t=-12.051、-17.462、-5.881,均P<0.001),血清FGF-2、估算肾小球滤过率(estimated glomerular filtration rate,eGFR)低于生存组(t=25.990、15.997,均P<0.001)。Pearson分析显示血清FGF-2与Scr、Cyc-C均呈负相关(r=-0.511、-0.449,P<0.001、0.002),与eGFR呈正相关(r=0.606,P<0.001)。血清FGF-23与Scr、Cyc-C均呈正相关,与eGFR呈负相关(r=0.610、0.522、-0.654,均P<0.001)。FGF-2、FGF-23联合应用的预测价值高于两指标单独应用(Z=2.120、2.034,P=0.034、0.042)。结论 脓毒症合并AKI患者的血清FGF-2水平明显降低、FGF-23水平明显升高,且与患者肾功能下降及短期预后不良有关,二者联合检测对预测脓毒症合并AKI短期预后的价值较高。

肾小管HIF-1α/miR-23a通路在脓毒血症急性肾损伤中的作用机制

目的探讨肾小管低氧诱导因子-1α(HIF-1α)/MicroRNA-23a(miR-23a)通路在脓毒血症急性肾损伤(SA-AKI)中的作用及相关作用机制。方法体外培养人近曲小管上皮细胞(HK-2细胞),采用脂多糖(LPS)处理HK-2细胞构建SA-AKI细胞模型。LPS处理的HK-2细胞分为LPS组、NC siRNA组、HIF-1αsiRNA组、anti-miR-NC组、anti-miR-23a组、HIF-1αsiRNA+miR-NC组、HIF-1αsiRNA+miR-23a组,以正常培养的HK-2细胞作为空白对照组(Control组)。采用qRT-PCR法检测细胞中HIF-1α、miR-23a基因表达;CCK-8法检测细胞活力;流式细胞术检测细胞凋亡;ELISA法检测细胞中炎性因子[白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子α(TNF-α)]水平;Western blot法检测细胞中HIF-1α蛋白、NF-κB通路蛋白表达。结果与Control组比较,LPS组HK-2细胞中HIF-1α蛋白和mRNA表达水平、miR-23a mRNA表达水平均升高,细胞活力降低,细胞凋亡率、细胞中IL-6、IL-1β和TNF-α水平均升高(P<0.05)。与LPS组比较,HIF-1αsiRNA组HK-2细胞中HIF-1α蛋白和mRNA表达水平、miR-23a mRNA表达水平均降低,细胞活力升高,细胞凋亡率、细胞中IL-6、IL-1β和TNF-α水平均降低(P<0.05)。与LPS组比较,anti-miR-23a组HK-2细胞中miR-23a mRNA表达水平降低,细胞活力升高,细胞凋亡率、细胞中IL-6、IL-1β和TNF-α水平均降低(P<0.05)。与HIF-1αsiRNA组比较,HIF-1αsiRNA+miR-23a组HK-2细胞中miR-23a mRNA表达水平升高,细胞活力降低,细胞凋亡率、细胞中IL-6、IL-1β和TNF-α水平均升高(P<0.05)。与Control组比较,LPS组HK-2细胞p-NF-κB-p65/NF-κB-p65、p-IκBα/IκBα比值均升高(P<0.05)。与LPS组比较,HIF-1αsiRNA组和anti-miR-23a组HK-2细胞p-NF-κB-p65/NF-κB-p65、p-IκBα/IκBα比值均降低(P<0.05)。与HIF-1αsiRNA组比较,HIF-1αsiRNA+miR-23a组HK-2细胞p-NF-κB-p65/NF-κB-p65、p-IκBα/IκBα比值均升高(P<0.05)。结论肾小管HIF-1α通过调控miR-23a表达调节NF-κB信号通路,从而参与LPS诱导的肾小管上皮细胞损伤。