Cathelicidin protects mice from Rhabdomyolysis-induced Acute Kidney Injury

Background: Cathelicidins are ancient and well-conserved antimicrobial peptides (AMPs) with intriguing immunomodulatory properties in both infectious and non-infectious inflammatory diseases. In addition to direct antimicrobial activity, cathelicidins also participate in several signaling pathways inducing both pro-inflammatory and anti-inflammatory effects. Acute kidney injury (AKI) is common in critically ill patients and is associated with high mortality and morbidity. Rhabdomyolysis is a major trigger of AKI.Objectives: Here, we investigated the role of cathelicidins in non-infectious Acute kidney Injury (AKI).Method: Using an experimental model of rhabdomyolysis, we induced AKI in wild-type and cathelicidin-related AMP knockout (CRAMP^-/-) mice. Results: We previously demonstrated that CRAMP^-/- mice, as opposed wild-type mice, are protected from AKI during sepsis induced by cecal ligation and puncture. Conversely, in the current study, we show that CRAMP^-/- mice are more susceptible to the rhabdomyolysis model of AKI. A more in-depth investigation of wild-type and CRAMP^-/- mice revealed important differences in the levels of several inflammatory mediators.Conclusion: Cathelicidins can induce a varied and even opposing repertoire of immune-inflammatory responses depending on the subjacent disease and the cellular context.     

急性肾损伤早期诊断标志物的研究进展

急性肾损伤是由各种原因引起的短时间内肾功能急剧下降而出现的临床综合征,其概念是由急性肾衰发展而来。由于传统的AKI诊断标准缺乏特异性以及敏感性,因此,近年来许多新型AKI早期标志物引起研究者的重视。文章就几种新型标志物的生物学功能、研究现状及前景进行综述。     

Acute kidney injury and rhabdomyolysis due to multiple wasp stings

In most patients, wasp stings cause local reactions and rarely anaphylaxis. Acute kidney injury and rhabdomyolysis are unusual complications of wasp stings. We report a case of acute kidney injury and rhabdomyolysis secondary to multiple wasp stings. A 55-year-old farmer developed multi organ dysfunction with acute kidney injury and rhabdomyolysis 3 days after he had sustained multiple wasp stings. The etiology of acute kidney injury is probably both rhabdomyolysis and acute tubular necrosis. He improved completely after hemodialysis and intensive care.     

Hepatocyte Necroptosis Induced by Ischemic Acute Kidney Injury in Rats

Abstract

While ischemic acute kidney injury (IAKI) is known often to cause hepatic injury, little is known about necroptosis involved in the hepatic injury. The purposes of this study were to identify necroptosis involvement and observe morphological changes of hepatocytes in hepatic injury induced by IAKI in rats. Based on successfully established IAKI rat models, enzyme-linked immunosorbent assay illustrated a significant higher level of tumor necrosis factor a in serums of IAKI animals. Tumor necrosis factor receptor a (TNFRa) and receptor interacting protein kinase 3 (RIPk3) showed significant higher expressions in immunoblot analyses and positive hepatocytes of RIPk3 immunohistochemical staining were also evident in livers of IAKI rats. In addition, light microscopy revealed necrotic lesions that contain hepatocytes ongoing necroptosis besides necrotic cells in IAKI livers. Electron microscopy revealed at least three types of necrotic hepatocytes, they were edema necrosis, vacuolization necrosis, and necroptosis. Hepatocytes undergoing necroptosis had both necrosis and apoptosis morphological characteristics, they were necrosis cytoplasm and apoptosis-like nucleus. Among cellular organelles of hepatocyte with necrosis, membranous structures, such as cell membrane, endoplasmic reticular system, and mitochondria were more vulnerable to the stress of IAKI and deformed nucleuses varied in shape and lytic or pyknotic chromatin appearances were noted under insults of IAKI. In conclusion, hepatocyte undergoing necroptosis, RIPk3-mediated necroptosis partly contributes to hepatic necrosis induced by IAKI. Both membranous structures and nucleuses of hepatocyte were vulnerable to ischemic acute kidney injury.     

Comparison of Outcomes of Mild and Severe Community- and Hospital-Acquired Acute Kidney Injury

PurposeAcute kidney injury (AKI) has shown an increasingly common occurrence among hospitalized patients worldwide. We determined the incidence and compared the short- and long-term outcomes of all stages of community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI), and identified predictors for such outcomes.Materials and MethodsThis observational, single-center, retrospective study identified patients admitted between January 2013 and December 2013 who developed CA-AKI or HA-AKI. Short- and long-term patient and renal outcomes were analyzed.ResultsAKI incidence was 14.3% (1882, CA-AKI 4.8% and HA-AKI 9.5%). The highest 30-day and 1-year mortality were recorded in the CA-AKI group. Thirty-day mortality rate was 11.4% in CA-AKI group and 5.7% in HA-AKI group (p<0.001). One-year mortality rates were 20.1% and 13.3%, respectively (p<0.001). More CA-AKI patients developed kidney failure with replacement therapy within 1 year (27, 4.3% vs. 18, 1.4% respectively, p<0.001).ConclusionIn conclusion, patients with CA-AKI had worse short- and long-term outcomes compared to HA-AKI patients. AKI severity and discharge serum creatinine were significant independent predictors of 30-day and 1-year mortality.     

Acute Kidney Injury in the Intensive Care Unit: The Most Reliable Way to Predict the Future is to Create It

How to cite this article: Tripathy S. Acute Kidney Injury in the Intensive Care Unit: The Most Reliable Way to Predict the Future is to Create It. Indian J Crit Care Med 2021;25(7):747–749.     

A Review of Oxidative Stress in Acute Kidney Injury: Protective Role of Medicinal Plants-Derived Antioxidants

Acute kidney injury (AKI) is the common clinical syndrome which is associated with increased morbidity and mortality. The severity extends from less to more advanced spectrums which link to biological, physical and chemical agents. Oxidative stress (OS)-related AKI has demonstrated the increasing of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and the decreasing of endogenous antioxidants. Medicinal plants-derived antioxidants can be ameliorated oxidative stress-related AKI through reduction of lipid peroxidation (LPO) and enhancement of activities and levels of endogenous antioxidants. Therefore, medicinal plants are good sources of exogenous antioxidants which might be considered the important remedies to ameliorate pathological alterations in oxidative stress-related AKI.     

CRRT在脓毒血症急性肾损伤患者救治中的临床研究

目的 集中探讨采用针对脓毒血症急性肾损伤(AKI)患者采用连续性肾脏代替治疗(continunous renal replacement therapy,CRRT)进行救治过程中的临床研究.方法 选取脓毒血症急性肾损伤患者200例,随机分为采用CRRT治疗的观察组和采用常规药物治疗的对照组,对采用不同方法进行治疗的两组患者救治过程中的临床指标变化进行对比分析.结果 在为期30天的临床疗效的比较中,观察组较对照组在生存率和死亡率的比较中,均具有明显生存优势,差异较大,具有统计学意义(P＜0.05).对照组在AKI分期的比较中,针对NⅠ、NⅡ,存活患者较死亡患者差异不大,不具有统计学意义(P＞0.05);在NⅢ的比较中,存活患者明显低于死亡患者,具有明显的统计学意义(P＜0.01);而观察组患者在AKI分期的比较中,在N1和NⅢ的比较中,存活患者较死亡患者差异较大,具有明显的统计学意义(P＜0.01);在合并症的发病率中的比较中,两组患者中存活患者的发病率明显低于死亡患者,差异较大,具有明显的统计学意义(P＜0.01);观察组患者中,存活患者较死亡患者在慢性阻塞性肺炎治疗的时间间隔的比较中差异不大,不具有统计学意义(P＞0.05);但是存活患者在从入ICU到入行CRRT的时间间隔明显短于死亡患者,差异较大,具有明显的统计学意义(P＜0.01).结论 CRRT在对于脓毒血症急性肾损伤患者治疗的过程中可有效的清除炎症因子,从发病机制上降低疾病的死亡率,维持内环境的相对稳定性,尽早使用CRRT治疗可有效地提高患者的30天存活率.     

血管紧张素Ⅱ在过度训练致大鼠急性肾损伤中的作用

目的:研究过度训练大鼠血浆和肾组织血管紧张素Ⅱ(AngⅡ)的变化及其意义。方法:健康雄性Wistar大鼠30只,随机分为对照组(n=6)和体力衰竭(力竭)组(n=24);建立大鼠游泳至力竭模型;于力竭即刻、力竭后6h、12h和24h,分别检测各组大鼠血清肌酐(Cr)、尿素(Ur)、磷酸肌酸激酶(CK)及尿γ-谷氨酰胺转肽酶(γ-GT)水平;观察肾组织结构变化和肾组织细胞凋亡;测定血浆和肾组织AngⅡ含量。结果:力竭即刻血清Ur、Cr、CK即明显升高,6h达高峰(P<0.05),24h恢复到对照水平;力竭后6h尿γ-GT明显升高,力竭后12h和24h升高更为明显(P<0.05);力竭即刻至力竭后24h大鼠肾组织结构变化轻微,但肾组织凋亡细胞明显增加(P<0.05);力竭即刻,血浆AngⅡ明显增高(P<0.01),力竭后6h～24h则逐渐降低,24h降低至对照组水平;力竭即刻至24h,肾组织AngⅡ进行性增高(P<0.01);肾组织AngII浓度与肾组织细胞调亡率呈明显正相关(r=0.76,P<0.01)。结论:过度训练大鼠血浆AngII浓度的变化主要参与力竭后早期肾损伤的发生,而肾组织中AngⅡ的增加可能通过组织细胞凋亡在力竭后延迟性肾损伤中发挥重要作用。     

冠状动脉旁路移植术后急性肾损伤的危险因素分析

目的 对比冠状动脉旁路移植术(coronary artery bypass grafting,CABG)后急性肾损伤(acute kidney injury,AKI)诊断标志物的表达水平,分析CABG后AKI的危险因素.方法 选取73例CABG患者作为研究对象,以CABG是否发生AKI分组为AKI组与对照组;对比两组患者术后24h血清肌酐(serum creatinine,Scr)、血清尿素氮(serum urea nitrogen,BUN)、尿液胱抑素C(urine cystatin C,Cys C)及肾损伤分子-1(kidney injury molecule-1,KIM-1)的表达水平;以AKI为作因变量,而患者的临床资料作为自变量,分析CABG后AKI的危险因素,并进行多因素及单因素Logistic回归分析,为CABG后AKI的预防策略提供依据.结果 AKI组与对照组术前Scr、BUN、Cys C及KIM-1的表达水平对比,差异均无统计学意义(P ＞0.05);AKI组术后Scr、BUN、Cys C及KIM-1的表达水平均显著高于对照组,两组数据差异具有统计学意义(t分别为3.586、3.728、4.325、3.089,P均小于0.05);单因素Logistic回归分析显示,年龄、高血压、移植血管桥数量、机械通气时间及术后低心排作为CABG后AKI的危险因素;多因素Logistic回归分析显示,年龄、移植血管桥数量及术后低心排作为CABG后AKI的独立危险因素,具有统计学意义(P＜0.05).结论 CABG后应密切监测患者的Scr、BUN、Cys C及KIM-1的表达水平,作为AKI的诊断标志物;年龄、移植血管桥数量及术后低心排作为CABG后AKI的独立危险因素,应严格进行术前评估、降低手术风险、围术期保护及改善肾功能,降低CABG后AKI发生的风险.     

伴急性肾功能衰竭横纹肌溶解综合征临床分析

目的探讨横纹肌溶解综合征伴急性肾功能衰竭（ARF）的临床特点、治疗及预后。方法对20例横纹肌溶解综合征伴ARF患者进行回顾性分析。结果20例伴ARF的横纹肌溶解综合征患者中，14例无尿。4例少尿；20例尿蛋白、隐血均阳性；血肌红蛋白（2961．2±285.3）mg／L，血肌酐（823．7±184．1）μmol／L，谷草转氨酶（712．3±82．6）U／L、谷丙转氨酶（978．4±71．9）IU／L、肌酸磷酸激酶（12753．5±18．2）U／L、CPK—MB（138．4±25．8）U／L；15例（75％）为高钾血症。给予补充液体、血液透析滤过等治疗后，18例（90％）存活，2例（10．0％）死于多器官功能障碍综合征；存活者出院时均脱离透析，14例血肌酐恢复正常，血清酶均恢复正常。结论横纹肌溶解综合征伴ARF时常表现为少尿型，高钾血症常见，血清酶学和血肌红蛋白明显升高有助于诊断，血液透析滤过治疗效果良好，存活者肾功能多可恢复。     

Acute Kidney Injury in Patients with Sepsis and Septic Shock: Risk Factors and Clinical Outcomes

Purpose

The aim of this study was to investigate clinical characteristics and risk factors of acute kidney injury (AKI) in patients with sepsis and septic shock. Additionally, we explored whether the severity of AKI affects on the clinical outcomes.

Materials and Methods

Data were collected retrospectively in a single center. Among 5680 patients who visited emergency department from January to December 2010, 992 patients with sepsis and septic shock were enrolled. Patients were divided into two groups, patients who developed AKI or not, to compare the baseline characteristics, and laboratory and physiologic data. Patients with AKI were subdivided according to its stages for survival analysis.

Results

AKI was developed in 57.7% of patients. Multivariable logistic regression analysis revealed that development of septic AKI was associated with older age, pre-existing chronic kidney disease, use of angiotensin converting enzyme inhibitor or angiotensin receptor blocker, presence of shock, positive blood culture results, and low white blood cell and platelet counts. Hospital mortality was higher in AKI group. Crude Kaplan-Meier survival curves demonstrated reduced 30-day survival rate was significantly associated with the severity of acute kidney injury.

Conclusion

The development of septic AKI was associated with poor clinical outcomes. Furthermore, the severity of AKI was associated with increased mortality.     

CRRT治疗应用于危重急性肾损伤对患者 肾功能及病死率的影响

目的 探讨连续性肾脏替代治疗（CRRT）应用于危重急性肾损伤对患者肾功能及病死率的影响。方法 回顾性分析2016年1月~2018年12月我院102例危重急性肾损伤患者的临床资料,根据患者所采取的治疗方式分成观察组60例和对照组42例。观察组采取原发病对症治疗及CRRT治疗,对照组接受原发病对症治疗。比较两组患者治疗1周后肾功能指标[血肌酐（Scr）、尿素氮（BUN）]变化及住院病死率。结果 治疗1周后,两组Scr、BUN水平均较治疗前降低,观察组Scr和BUN分别为（173.35±43.18）μmol/L和（13.12±4.06）mmol/L,低于对照组的（221.73±60.56）μmol/L和（16.71±4.17）mmol/L,差异具有统计学意义（P＜0.05）;观察组患者28 d住院病死率低于对照组（31.67% vs 57.14%）,差异具有统计学意义（P＜0.05）。结论 CRRT治疗可以更有效地改善急性肾损伤患者的肾功能,并显著降低患者住院病死率。     

脓毒症继发急性肾损伤过程中的凝血变化

目的 脓毒症继发急性损伤是脓毒症患者死亡的重要原因之一,凝血变化是急性肾损伤重要因素。本研究旨在筛选脓毒症过程中同急性肾损伤相关的凝血指标。方法 本研究收集外科、急诊及呼吸重症监护室的脓毒症患者,纳入132例脓毒症患者,其中合并急性肾损伤64例,非急性肾损伤68例。收集各组患者一般资料及入ICU第1个24h内各项实验室指标,利用Logistic回归分析及Cox回归分析进行统计学分析。结果 AKI组与非AKI组相比,抗凝血酶Ⅲ(P=0.007)显著降低,D-二聚体则显著升高(P=0.006)。二分类变量Logistic回归显示,D-二聚体与抗凝血酶Ⅲ为脓毒症继发AKI的危险因素,OR值分别为3.018(95%CI:1.127～8.083)和2.89(95%CI:1.181～7.070),P<0.05。利用Cox回归分析显示仅有D-二聚体同病死率相关,HR值1.347(95%CI:1.081～1.677),P=0.008。结论 D-二聚体和抗凝血酶Ⅲ是脓毒症继发AKI发生的独立危险因素。D-二聚体升高同脓毒症继发AKI的28d病死率高相关。     

Acute Kidney Injury in Pediatric Patients Receiving Allogeneic Hematopoietic Cell Transplantation: Incidence,Risk Factors,and Outcomes

Acute kidney injury (AKI) is a common adverse event after hematopoietic cell transplantation (HCT). AKI is associated with early death or chronic kidney disease among transplant survivors. However, large-scale pediatric studies based on standardized criteria are lacking. We performed a retrospective analysis of 1057 pediatric patients who received allogeneic HCT to evaluate the incidence and risk factors of AKI according to AKI Network criteria within the first 100 days of HCT. We also determined the effect of AKI on patient survival. The 100-day cumulative incidences of all stages of AKI, stage 3 AKI, and AKI requiring renal replacement therapy (RRT) were 68.2%?±?1.4%, 25.0%?±?1.3%, and 7.6%?±?.8%, respectively. Overall survival at 1 year was not different between patients without AKI and those with stage 1 or 2 AKI (66.1% versus 73.4% versus 63.9%, respectively) but was significantly different between patients without AKI and patients with stage 3 AKI with or without RRT requirement (66.1% versus 47.3% versus 7.5%, respectively; P?<?.001). Age, year of transplantation, donor type, sinusoidal obstruction syndrome (SOS), and acute graft-versus-host disease (GVHD) were independent risk factors for stages 1 through 3 AKI. Age, donor, conditioning regimen, number of HCTs, SOS, and acute GVHD were independent risk factors for AKI requiring RRT. Our study revealed that AKI was a prevalent adverse event, and severe stage 3 AKI, which was associated with reduced survival, was common after pediatric allogeneic HCT. All patients receiving allogeneic HCT, especially those with multiple risk factors, require careful renal monitoring according to standardized criteria to minimize nephrotoxic insults.