表观遗传修饰在急性肾损伤向慢性肾脏病转变中的作用

急性肾损伤(acute kidney injury,AKI)后即使肾功能完全恢复也可能会发展为慢性肾脏病(chronic kidney disease,CKD),但AKI向CKD转变的机制尚不清楚。作为基因表达的重要调控者,表观遗传修饰可能在AKI向CKD转变中发挥重要作用。表观遗传变化由缺氧诱导,进而促进炎性因子相关基因的表达和胶原蛋白分泌。本文就表观遗传修饰在AKI转化为CKD中的作用、表观遗传学标志物在诊断AKI慢性转归中的价值,以及靶向干预表观遗传在防治AKI向CKD转变中的潜在作用进行综述。     

心脏术后急性肾损伤的研究进展

急性肾损伤(acute kidney injury,AKI)是心脏术后常见的严重并发症,AKI不仅明显增加住院费用及住院时间,而且增加手术死亡率。心脏术后AKI是多因素相互作用的结果,除了术前肾功能不全、糖尿病等危险因素以外,最近研究发现,围手术期输血、术后血管紧张素转化酶抑制剂/血管紧张素受体抑制剂(ACEI/ARB)等药物的应用也是心脏术后AKI的危险因素。AKI风险评估模型的建立与应用、一些新的生物学标志物的发现可以为临床医师早期预测、诊断和治疗AKI提供重要的客观数据。该文就心脏术后AKI的定义、相关危险因素和生物标志物的研究现状作一简介。     

别嘌醇与慢性肾脏病的研究进展

<正>高尿酸血症(hyperuricemia,HUA)是慢性肾脏病(chronic kidney diseases,CKD)患者发生心血管事件、死亡的预测因素。别嘌醇(allopurinol)作为经典的抑制尿酸生成的药物,它除了降低尿酸可能还通过降低晚期糖基化终末产物(AGEs)的水平,阻止血管紧张素II的作用,可能具有延缓CKD的进展,减少CKD患者并发心血管事件的作用。     

巨噬细胞极化参与急性肾损伤-慢性肾脏病转化的研究进展

<正>流行病学和病因学研究均显示急性肾损伤(acute kidney injury,AKI)和慢性肾脏病(chronic kidney disease,CKD)相互之间的紧密联系。慢性肾脏病是发生AKI的危险因素,而AKI后进展为慢性肾脏病的风险上升[1]。AKI转化慢性肾脏病的机制在近10年来得到了科研人员的重视和研究。主流观点认为不断进展的肾脏纤维化(fibrosis)是AKI进展至CKD的主要病理特点[2]。导致纤维化的原因在于AKI后的修复不良(maladaptive repair)。过去已有研究人员从肾小管缺氧[3],纤维母细胞增生[2],巨噬细胞等炎症细胞的调控[4~6],去分化的肾小     

重视“微观辨证”在慢性肾脏病治疗中的作用

慢性肾脏病（Chronic kidney disease,CKD）是缓慢进行性发展的临床病证,由于不良预后和近年来不断增高的发病率日益受到关注。现代医学以血管紧张素转换酶抑制剂（ACEI）、血管紧张素受体阻断剂（ARB）为代表延缓肾衰竭进展的治疗措施虽取得了一定的疗效,但仍不能完全满足临床的需要。     

甲基巴多索隆治疗2型糖尿病和慢性肾脏病4期

<正>2型糖尿病是发达和发展中国家进展性慢性肾脏病(chronic kidney disease,CKD)的最重要原因。为了延缓疾病进展,采用过各种治疗方法,包括限制饮食蛋白、控制血糖、控制高血压等,也已经取得了一些疗效不一的结果。虽然肾素-血管紧张素-醛固酮系统(renin-angiotensin-aldosterone system,RAAS)抑制剂可延缓糖尿病肾病的进展,但风险也很高。过去10年中新型药物在后期临床试验中均未被证明有效。氧化应激和抗氧化能力受损,能够促进CKD进展。在动物CKD中,氧化应激和     

本刊可直接使用缩写的一些常用词汇(一)

<正>本刊对以下一些大家都比较熟悉的常用词汇将直接用缩写,即第一次出现时,可以不标注中文。1.ACEI:angiotensin converting enzyme inhibitors,血管紧张素转换酶抑制剂2.AIDS:acquired immunodeficiency syndrome,艾滋病3.AKI:acute kidney injury,急性肾损伤4.ARB:angiotensin receptor blockers,血管紧张素受体阻断剂5.ARF:acute renal failure,急性肾衰竭     

巢式病例对照研究非心血管手术后急性肾损伤危险因素

目的 探索非心血管手术术后发生急性肾损伤(acute kidney injury,AKI)的发病率,采用巢式病例对照研究进行危险因素分析预测. 方法 回顾性分析2012年1月～2014年10月19 132例非心血管手术病例资料,依据全球改善肾脏病预后组织(kidney disease improving global outcomes,KDIGO)指南,以血肌酐的改变为标准进行术后AKI诊断.术后血肌酐值较术前升高达到AKI诊断标准的病例28例(病例组),采用巢式病例对照研究方法,按1∶6匹配同期同类未发生AKI的手术病例168例作为对照组,探讨年龄、性别、BMI、高血压、糖尿病、术前使用血管紧张素转化酶抑制剂(angiotension converting enzyme inhibitors,ACEI)/血管紧张素Ⅱ受体拮抗剂(angiotensin receptor blockers,ARB)类药物、低蛋白血症、术中低血压等因素对术后AKI的影响. 结果 19 132例非心血管手术患者中,28例(0.146％)发生了术后AKI.发生AKI的28例病例手术类型分别为:14例(50％)消化道手术,6例(22％)腹腔脏器手术,2例(7％)妇产科手术,2例(7％)泌尿外科手术,2例(7％)骨科手术,2例(7％)其他.所有AKI病例中急诊手术达15例.单因素分析提示高血压,低蛋白血症,术前应用ACEI或ARB类药物、术中低血压、输血、急诊手术可能与术后AKI有关(P＜0.05).多因素Logistic回归分析显示术中低血压,术前应用ACEI或ARB类药物,低蛋白血症,急诊手术为术后发生AKI的危险因素. 结论 AKI在非心血管手术的发病率并不罕见.发生AKI的手术种类多为干扰到全身血流动力学、对内环境影响较大的手术.术中低血压、术前应用ACEI或ARB类药物、低蛋白血症、急诊手术可作为非心血管手术术后发生AKI的预警因素.     

本刊可直接使用缩写的一些常用词汇(一)

<正>本刊对以下一些大家都比较熟悉的常用词汇将直接用缩写,即第一次出现时,可以不标注中文。1.ACEI:angiotensin converting enzyme inhibitors,血管紧张素转换酶抑制剂2.AIDS:acquired immunodeficiency syndrome,艾滋病3.AKI:acute kidney injury,急性肾损伤4.ARB:angiotensin receptor blockers,血管紧张素受体阻断剂5.ARF:acute renal failure,急性肾衰竭     

胰十二指肠切除术后急性肾损伤的危险因素分析

目的探讨开腹胰十二指肠切除术后急性肾损伤(acute kidney injury, AKI)的危险因素。方法回顾性分析2011年11月—2018年4月行开腹胰十二指肠切除术患者389例,男219例,女170例,年龄25～79岁,ASAⅠ—Ⅳ级。收集相关围术期资料,统计术后AKI、性别、BMI、合并梗阻性黄疸、服用血管紧张素转换酶抑制剂(ACEI)或血管紧张素Ⅱ受体阻滞剂(ARB)类降压药和术后Hb等情况。采用多因素Logistic回归分析术后AKI的独立危险因素。结果术后AKI有46例(11.8%)。多因素Logistic回归分析显示,男性(OR=2.33,95%CI 1.13～4.82,P=0.023)、BMI≥24 kg/m~2(OR=2.39,95%CI 1.23～4.65,P=0.010)、合并梗阻性黄疸(OR=3.29,95%CI 1.70～6.37,P0.001)、服用ACEI或ARB(OR=3.93,95%CI 1.08～14.38,P=0.038)和术后Hb中重度下降(OR=3.81,95%CI 1.13～12.89,P=0.031)是开腹胰十二指肠切除术后AKI的独立危险因素。结论男性、BMI≥24 kg/m~2、合并梗阻性黄疸、服用ACEI或ARB、术后Hb中重度下降是开腹胰十二指肠切除术后AKI的独立危险因素。     

Characteristics and risk factors of acute kidney injury progressed to chronic kidney disease: a prospective,observational cohort study

Objective To prospectively investigate the characteristics of acute kidney injury (AKI) that progressed to chronic kidney disease (CKD) (AKI to CKD) in patients hospitalized for AKI, determine the risk factors of AKI to CKD, and preliminarily evaluate the performance of clinical risk factor model for predicting AKI to CKD. Methods This was a prospective, observational cohort study. Patients hospitalized for AKI and without a prior CKD [estimated glomerular filtration rate (eGFR)＜60 ml?min-1?(1.73 m2)-1] were enrolled in Nanfang Hospital of Southern Medical University from April 2015 to December 2019. Survived patients were followed 90 days after AKI and the renal function 90 days post AKI was determined. The primary endpoint was AKI to CKD, defined as new-onset CKD [eGFR＜60 ml?min-1?(1.73 m2)-1 90 days post AKI]. According to AKI progressed to CKD or not, AKI patients were divided into two groups (with or without AKI to CKD). The baseline clinical data of demographics, comorbidities, baseline renal function, AKI severity, receiving hemodialysis or not, and other lab parameters were compared between two groups. The logistic regression model was used to analyze the risk factors of AKI to CKD. Finally, receiver operator characteristic (ROC) curve was drawn to evaluate the performance of clinical risk factor model for predicting AKI to CKD. Results A total of 168 patients with AKI was enrolled in this study[male, n=91; female, n=77; age (44.0±18.4) years], in which 64 patients (38.1%) developed new-onset CKD 90 days post AKI and 104 patients (61.9%) did not. Compared to those without AKI to CKD, patients with AKI to CKD were older, and had a higher proportion of hypertension, lower levels of eGFR and hemoglobin, higher proportion of receiving hemodialysis, and higher level of discharged serum creatinine (all P＜0.05). There was no significant difference in the proportion of diabetes and use of RAS inhibitors, urine protein level, and other lab parameters between two groups. Multivariate logistic regression analysis shows that receiving hemodialysis (OR=2.516, 95%CI 1.251-5.060, P=0.010), hypertension (OR=2.446, 95%CI 1.124-5.324, P=0.024), and lower baseline eGFR (OR=0.975, 95%CI 0.950-0.999, P=0.043) were the independent risk factors for AKI to CKD. The clinical risk factor model including age, receiving hemodialysis, hypertension, and baseline eGFR produced moderate performance for predicting AKI to CKD, with the area under ROC curve of 0.712, 95%CI 0.634-0.790. Conclusions AKI survivors are at high risk for developing CKD. Receiving hemodialysis, hypertension, and lower baseline eGFR are independent risk factors for predicting AKI to CKD. More studies are needed to improve the performance of clinical risk factor model for early detecting high risk patients who will develop AKI to CKD.     

Potential Therapeutic Targets for Cisplatin-Induced Kidney Injury: Lessons from Other Models of AKI and Fibrosis

The effectiveness of cisplatin, a mainstay in the treatment of many solid organ cancers, is hindered by dose-limiting nephrotoxicity. Cisplatin causes AKI in 30% of patients. Patients who do not develop AKI by clinical standards during treatment are still at risk for long-term decline in kidney function and the development of CKD. The connection between AKI and CKD has become increasingly studied, with renal fibrosis a hallmark of CKD development. To prevent both the short- and long-term effects of cisplatin, researchers must use models that reflect both types of pathology. Although a lot is known about cisplatin-induced AKI, very little is known about the mechanisms by which repeated low levels of cisplatin lead to fibrosis development. In this review, strategies used in various rodent models to prevent kidney injury, its progression to fibrosis, or both, are examined to gain mechanistic insights and identify potential therapeutic targets for cisplatin-induced kidney pathologies. Reviewing the results from these models highlights the diverse and highly complex role of cell death, cell senescence, endoplasmic reticulum stress, autophagy, and immune cell activation in acute and chronic kidney injuries. The use of several models of kidney injury is needed for development of agents that will prevent all aspects of cisplatin-induced kidney injury.     

Urinary angiotensinogen,related factors and clinical implications in normotensive autosomal dominant polycystic kidney disease patients

Background: Although several lines of evidence suggest that renin angiotensin system (RAS) proteins are synthesized by cyst epithelium and dilated tubules, role of intrarenal RAS in the progression of otozomal dominant polycystic kidney disease (ADPKD) is not well known. We aimed to study the levels and clinical correlations of urinary angiotensinogen (UAGT) in normotensive ADPKD patients compared with age- and sex-matched healthy subjects. Methods: The study included 20 normotensive ADPKD patients (F/M: 11/9) and 20 age and sex matched healthy controls (F/M: 9/11). Diagnosis of ADPKD was made based on Ravine criteria. Twenty-four hours ambulatory blood pressure monitoring (ABPM) was performed. Serum concentrations of creatinine, Na, K, uric acid, and urinary concentrations of Na, K, uric acid, creatinine, protein and albumin were measured. UAGT were measured via commercially available ELISA kit. Results: ADPKD patients had higher urinary albumin:creatinine ratio (UAIb/UCrea) than healthy controls (p?r?=?0.785, p?=?0.01), and UAIb/UCrea (r?=?0.681, p?=?0.01) in normotensive ADPKD patients. Conclusion: This pilot study demonstrates that UAGT levels tend to be elevated and are correlated with proteinuria and albuminuria in normotensive ADPKD patients during relatively early stages of the disease.     

Acute kidney injury in idiopathic nephrotic syndrome of childhood is a major risk factor for the development of chronic kidney disease

Background: Acute kidney injury (AKI) is an important complication of idiopathic nephrotic syndrome (INS) and is associated with adverse outcomes, especially the development of chronic kidney disease (CKD). We aimed to determine the clinical profile of children with INS who developed AKI and its short-term outcome.

Material and methods: This prospective study was conducted from March 2014 to October 2015. A total of 119 children of INS (age: 2–18 years) fulfilling the pediatric RIFLE criteria for the diagnosis of AKI were enrolled and followed up for 3 months to determine the outcome. Factors predisposing to CKD were studied.

Results: The mean age at presentation was 8.8?±?3.59 years and males were 74 (62.2%). At presentation, 61 (51.3%) children were in Risk category, 43 (36.1%) in Injury category, and 15 (12.6%) in Failure category. Most of them (41.2%) had steroid-resistant nephrotic syndrome (SRNS) and focal segmental glomerulosclerosis (FSGS) on histopathology (33.6%).

Infections were the major predisposing factor for AKI in 67 (56.3%) cases. Drug toxicity was the next common, found in 52 (43.7%) children. A total of 65 (54.6%) children recovered from AKI, while 54 (45.4%) did not. CKD developed in 49 (41.2%) non-recovered cases and 5 (4.2%) children succumbed to acute illness. SRNS, cyclosporine use, FSGS on histology, and drug toxicity were significant factors associated with the development of CKD.

Conclusion: AKI associated with INS is a reversible condition in most cases but it can progress to CKD, especially among those who have SRNS, FSGS, and drug toxicity.     

Donation after cardiac death liver transplant recipients have an increased frequency of acute kidney injury

Donation after cardiac death (DCD) liver transplantation is associated with an increased frequency of hepato-biliary complications. The implications for renal function have not been explored previously. The aims of this single-center study of 88 consecutive DCD liver transplant recipients were (1) to compare renal outcomes with propensity-risk-matched donation after brain death (DBD) patients and (2) in the DCD patients specifically to examine the risk factors for acute kidney injury (AKI; peak creatinine ≥2 times baseline) and chronic kidney disease (CKD; eGFR <60 mL/min/1.73 m(2) ). During the immediate postoperative period DCD liver transplantation was associated with an increased incidence of AKI (DCD, 53.4%; DBD 31.8%, p = 0.004). In DCD patients AKI was a risk factor for CKD (p = 0.035) and mortality (p = 0.017). The cumulative incidence of CKD by 3 years post-transplant was 53.7% and 42.1% for DCD and DBD patients, respectively (p = 0.774). Importantly, increasing peak perioperative aspartate aminotransferase, a surrogate marker of hepatic ischemia reperfusion injury, was the only consistent predictor of renal dysfunction after DCD transplantation (AKI, p < 0.001; CKD, p = 0.032). In conclusion, DCD liver transplantation is associated with an increased frequency of AKI. The findings suggest that hepatic ischemia reperfusion injury may play a critical role in the pathogenesis of post-transplant renal dysfunction.     

Patterns of kidney injury in pediatric nonkidney solid organ transplant recipients

The incidence of acute kidney injury (AKI) and its impact on chronic kidney disease (CKD) following pediatric nonkidney solid organ transplantation is unknown. We aimed to determine the incidence of AKI and CKD and examine their relationship among children who received a heart, lung, liver, or multiorgan transplant at the Hospital for Sick Children between 2002 and 2011. AKI was assessed in the first year posttransplant. Among 303 children, perioperative AKI (within the first week) occurred in 67% of children, and AKI after the first week occurred in 36%, with the highest incidence among lung and multiorgan recipients. Twenty‐three children (8%) developed CKD after a median follow‐up of 3.4 years. Less than 5 children developed end‐stage renal disease, all within 65 days posttransplant. Those with 1 AKI episode by 3 months posttransplant had significantly greater risk for developing CKD after adjusting for age, sex, and estimated glomerular filtration rate at transplant (hazard ratio: 2.77, 95% confidence interval, 1.13‐6.80, P trend = .008). AKI is common in the first year posttransplant and associated with significantly greater risk of developing CKD. Close monitoring for kidney disease may allow for earlier implementation of kidney‐sparing strategies to decrease risk for progression to CKD.     

Protecting the Kidney in Liver Transplant Candidates: Practice‐Based Recommendations From the American Society of Transplantation Liver and Intestine Community of Practice

Acute kidney injury (AKI) and chronic kidney disease (CKD) are common in patients awaiting liver transplantation, and both have a marked impact on the perioperative and long‐term morbidity and mortality of liver transplant recipients. Consequently, we reviewed the epidemiology of AKI and CKD in patients with end‐stage liver disease, highlighted strategies to prevent and manage AKI, evaluated the changing liver transplant waiting list's impact on kidney function, delineated important considerations in simultaneous liver–kidney transplant selection, and projected possible future transplant policy changes and outcomes. This review was assembled by experts in the field and endorsed by the American Society of Transplantation Liver and Intestinal Community of Practice and Board of Directors and provides practice‐based recommendations for preservation of kidney function in patients with end‐stage liver disease.     

Incidence and mortality of postoperative acute kidney injury in non-dialysis patients: comparison between the AKIN and KDIGO criteria

Objectives This retrospective study determines whether the kidney disease: improving global outcomes (KDIGO) criteria are superior to acute kidney injury network (AKIN) criteria in detecting non-dialysis AKI events and predicting mortality in chronic kidney disease (CKD) patients after surgery. Methods Surgical patients who were admitted to the intensive care unit were enrolled. Non-dialysis AKI cases were defined using either KDIGO or AKIN creatinine criteria and stratified by CKD stages. The adjusted hazard ratios (AHRs) for in-hospital mortality are compared to those without AKI. The cumulative survival curves and the predictability for mortality are accessed by Kaplan–Meier method and calculating the area under the curve (AUC) for the receiver operating characteristic (ROC) curve, respectively. Results From a total of 826 postoperative patients, the overall in-hospital mortality rate was 11.6% (96 cases) and that for AKI according to KDIGO and AKIN criteria was 30.0% (248 cases) and 31.0% (256 cases). The cumulative survival curve stratified by CKD and AKI stages were comparable between KDIGO and AKIN criteria. The discriminative power for mortality stratified by CKD stages for KDIGO and AKIN criteria are as followed: all subjects: 0.678 versus 0.670 (both ps?<0.001); non-CKD: 0.800 versus 0.809 (both ps?<0.001); early-stage CKD: 0.676 versus 0.676 (both ps?<0.001); late-stage CKD: 0.674 versus 0.660 (ps were?<0.001 and 0.003). Conclusion The KDIGO criteria are superior to AKIN criteria in predicting mortality after surgery, especially in those with advanced CKD.     

Chronic-on-acute kidney injury

Although older teaching suggested that patients who survived an episode of acute kidney injury (AKI) had a benign course, recent studies have demonstrated that AKI is strongly associated with increased risk for development of progressive chronic kidney disease (CKD) and longer-term mortality. Much as we understand that CKD predisposes to the development of AKI, we must recognize that the relationship is bidirectional and that our patients with AKI are at risk for chronic-on-acute kidney disease.     

Perioperative management of the patient with chronic kidney disease

The prevalence of chronic kidney disease (CKD) is increasing. Perioperative management of patients with CKD aims to control modifiable risk factors associated with acute kidney injury (AKI). AKI on the background of CKD may lead to dialysis dependency. CKD has widespread cardiovascular, endocrine, metabolic and haematological effects. Preoperative assessment and preparation require multidisciplinary input from the surgical, anaesthetic and nephrology teams. Perioperative care should ensure the correction of hypovolaemia, maintenance of renal blood flow and perfusion pressure, prevention of radiocontrast-induced nephrotoxicity, avoidance of nephrotoxic drugs and treatment of urinary tract obstruction.