急性肾损伤的非肾脏替代治疗

急性肾损伤是由许多不同病因所致肾脏结构和功能改变的临床综合征.无论何种原因导致的急性肾损伤,防治原则包括改善循环、合理控制容量状态、避免使用肾毒性药物、营养支持等.     

脓毒症急性肾损伤发病机制的研究进展

脓毒症急性肾损伤是脓毒症多器官功能障碍的表现之一.当出现急性肾损伤时,往往提示病情危重.脓毒症急性肾损伤主要与肾脏血流动力学改变、缺血再灌注损伤、直接的炎症损伤、凝血和血管内皮细胞功能紊乱及细胞凋亡等有关.     

关注儿童用药后的肾损伤

药物性肾损伤是儿童急性肾损伤的主要原因之一。药物经由肾脏代谢排泄时导致肾小管上皮细胞损伤、肾脏免疫炎症,或导致肾内血流动力学改变,或形成结晶堵塞肾小管。临床主要表现为急性肾损伤、急性肾小管坏死、急慢性间质性肾炎、结晶性肾病、肾病综合征、肾小管功能障碍等。应用生物标志物可以早期监测药物性肾损伤。临床工作中应及时纠正药物性肾损伤的高危因素,及时停用相关药物和监测肾功能,力求早期诊断,早期干预,改善预后。     

急性肾损伤的诊断与治疗进展

急性肾损伤除继发于肾脏本身的疾病外,也可继发于多器官功能障碍综合征、新生儿呼吸窘迫综合征、脓毒症、胃肠道液体丢失、心脏外科手术及使用肾毒性的药物或食物等多种其他系统的疾病.近年来,国际上多个学科的专家,对急性肾损伤的定义、诊断分期、治疗和预后等统一认识,有了新的观点,发布了新的指南.另外,用于早期设别急性肾损伤的生物学标志有较多的报道,为了解急性肾损伤的诊疗现状,现通过改善全球肾脏病预后组织2012年3月发布的《急性肾损伤的临床实践指南》和近年有关文献,对急性肾损伤的临床实用知识,尤其是新的观念作一综述.     

急性肾损伤的定义、诊断及治疗

近年来凼际肾脏病和急救医学界趋向于用急性肾损伤(AKI)来取代急性肾衰竭(ARF)的概念,这对于早期诊断、早期治疗和降低病死率具有更积极的意义.新的AKI诊断标准为48 h内血肌酐上升26.5 μmol/L(0.3 mg/dl)或较原先水平增高50%;和(或)尿量减少<0.5 ml/(kg·h),持续6 h以上.AKI诊断的新生物学标志物正处于研究中.AKI的治疗仍以肾脏替代治疗为主,但目前关于肾脏替代治疗的时机、模式、剂量尚存在争议.     

PAX2与急慢性肾脏疾病研究进展

配对盒基因2(paired box2,PAX2)是一种核转录因子,表达在发育期肾脏。研究表明PAX2通过与PTIP的相互作用使染色质处于可转录状态,与Grg4的相互作用削弱了其与PTIP结合而抑制转录。 PAX2在急性肾损伤时再表达,参与促进细胞增殖修复。先天PAX2基因突变与先天性肾脏输尿管异常密切相关。在慢性肾脏疾病,PAX2起到促进增殖及囊肿形成的作用。该文就PAX2的功能及其在急性肾损伤和慢性肾脏疾病中作用的相关研究进行综述。     

小儿急性肾衰竭诊断标准及治疗进展

急性肾衰竭是儿科临床常见的危重症肾脏疾病。早期诊断、早期治疗是改善儿童急性肾衰竭预后、提高患儿生存率的关键。现重点介绍小儿急性肾衰竭诊断标准及治疗方案研究进展，从急性。肾损伤的定义、诊断标准和分期到急性肾衰竭的治疗措施进行阐述。     

血液净化技术在儿童急性肾损伤中的应用（附五例报告）

目的 探讨血液净化技术在儿童急性肾损伤中的应用体会.方法 5例急性肾损伤患儿,其中多囊肾1例,孤立肾1例,严重脓毒症合并多器官功能衰竭1例,急性药物（氯氮平）中毒1例,农药（甲哌嗡）中毒1例.该5例患儿均进行了血液净化治疗,其中多囊肾患儿、孤立肾患儿以及严重脓毒症合并多器官功能衰竭患儿均进行血液透析治疗,急性药物（氯氮平）中毒和农药（甲哌嗡）中毒患儿均给予了血液灌流治疗,回顾性分析这5例急性肾损伤患儿进行血液净化治疗过程中的临床特点,治疗药物及治疗效果.结果 5例患儿均顺利置管并分别完成了相应的血液净化治疗,平均持续时间为30 h（16 ～62 h）,治疗前血Cr、BUN分别为（387.2＆#177;195.4）μmol/L、（37.5＆#177;12.8）mmol/L,治疗48 h后均恢复至正常水平；治疗12h后K＋、Na＋、Ca2＋、HCO3-紊乱状态恢复正常.放弃治疗1例,治愈4例.结论 儿童急性肾损伤的病因种类多,根据病因及个体差异选择合适的血液净化模式,有助于改善肾脏功能,降低病死率.     

早产儿肾损伤及监测

急性肾损伤（AKI）是新生儿重症监护病房常见的并发症,不仅造成早产儿高病死率,还引起成年后多种慢性肾疾病。早产儿出生时肾脏发育不成熟,在生后特定时间窗内肾脏持续加速发育,但受孕期和产后多种因素影响,容易发生急性肾损伤。目前传统的评价肾损伤的指标为血清肌酐和尿量,但其早期敏感性和特异性问题日渐受到关注。最近多种新的生物学标志物被发现可用来早期识别急性肾损伤,本文就早产儿急性肾损伤、影响因素及肾功能评价和防治进行概述,为提高早产儿急性肾损伤早期诊治水平和远期生存质量提供参考。     

儿童急性肾损伤的概念与诊断

急性肾损伤(AKI)的概念将逐渐取代传统急性肾衰竭(ARF)的概念.AKI的定义为病程在3个月以内,包括血、尿、组织学及影像学检查所见的肾脏结构与功能异常.2005年的阿姆斯特丹会议同时决定将48 h内血肌酐(Scr)上升≥26.5 μmol/L或原Scr值增长≥50%和(或)尿量＜0.5 mL/(kg*h)达6 h定义为AKI的诊断标准,并制定了病情分期标准.但Scr在反映肾功能的速度和精度方面存在不足,故需要寻找敏感性和特异性更好,能够预测疾病预后并具有AKI病因特异性的生物学指标.     

Bibliometric data: a disaster for many non-American biomedical journals

Bibliometric data published by the Institute of Scientific Information in Philadelphia (ISI), and which was previously discussed in Acta Paediatrica , has increasingly been used despite all the relevant and severe criticism that has been raised against this method of evaluating individual research results and grading scientific journals. It is obvious that the present trend regarding the use of bibliometric data as a basis for priorities and funding of research and for the promotion of individual scientists favours American-oriented research projects at the expense of those that are based on concepts of predominantly European relevance.

Conclusion: For the future of non-American research, it is important that no single super-power, i.e. the USA, should dominate scientific priorities. The condition for efficient European competition is that European Centres with high levels of competence for creative research and training of scientists from all over the world are established. In addition, it is important that the results of European research are published in prestigious European journals, as was the situation before World War II.     

alpha -SMOOTH MUSCLE ACTIN DISTRIBUTION IN THE PULMONARY VASCULATURE COMPARING HYPOPLASTIC AND NORMAL FETAL LUNGS

We investigated the intra-acinar pulmonary vascular muscularization in the developing human fetal lung between the 17th and 24th gestational weeks, that is, during the canalicular phase of lung development. Fifteen hypoplastic and 25 normal developed lungs were included in this study using monoclonal alpha -smooth muscle (sm) actin antibodies for smooth muscle detection. Computer-aided image analysis was performed for morphometrical measurements and statistical evaluation. Alphasm-actin-immunoreactive intra-acinar vessels down to a luminal diameter of less than 10 mu m were detected in hypoplastic as well as in normally developed lungs. Crucial differences presented as follows: significantly higher density of intra-acinar vessels, especially due to alpha -sm-actin-negative vessels less than 30 mu m in luminal diameter, in the control group; significantly higher alpha -sm-actin immunoreactivity per section unit as well as per vessel in the hypoplastic lung group. As suggested by others, alpha-sm-actin-positive cells of the intra-acinar vessel wall in the developing human lung were demonstrated to be smooth muscle cells, their immediate precursors, and pericytes. We conclude that the increased alpha -sm-actin immunoreactivity represents muscularization of the vessel wall in functional terms and may be regarded as one structural cause among others for the establishment of persistent fetal circulation in hypoplastic lungs.     

Whole-body mineral measurements in Swedish adolescents at 17 years compared to 15 years of age

Aim: To provide reference data for bone mineral variables in 15- and 17-y-old adolescents and to analyse the relationships between these variables and measures of bone and body size, gender, puberty, growth, various lifestyle and environmental factors and socioeconomic background.

Methods: In the same 321 randomly selected adolescents (147 boys and 174 girls) living in two different regions of Sweden, the total bone mineral content (TBMC), bone area (BA) and total bone mineral density (TBMD) were assessed by dual-energy X-ray absorptiometry at ages 15 and 17 y. The effects of bone and body size, gender, growth, sexual maturity, physical activity, region of domicile, social conditions, food habits, smoking and alcohol intake on TBMC and TBMD were examined in multivariate analyses.

Results: In the 15-y-old adolescents, BA, height, gender, physical activity, maturity and weight explained 91% and 48%, of the variance in TBMC and TBMD, respectively. In similar analyses in the 17-y-olds, the corresponding figures were 92% and 62%, respectively, when BA, height, growth, physical activity, gender and region emerged as significant in the model. In all these analyses, BA explained most of the variance in TBMC and TBMD. No significant reduction of variance was found when different measures of social conditions, smoking, food habits, alcohol or dietary intakes of energy, calcium or vitamin D were included in the models. The reason why region of domicile had a significant impact on TBMC in the 17-y-olds is not known. The fact that the normal fluoride concentration in drinking water (1.1 mg/L) is 10 times higher in the region where TBMC was higher than in the other region is an interesting observation.

Conclusion: Almost 90% of the variance in TBMC and 50% of that in TBMD was explained by measures of bone and body size and only a few percent by gender, physical activity, Tanner stage, growth and region of domicile.     

The potential role of rapamycin in pediatric transplantation as observed from adult studies

Although pediatric patient and renal graft survival rates have shown marked improvements during the past decade, the persistent toxicities of immunosuppressive drugs and chronic allograft attrition remain major obstacles in transplant therapy. Results in adult patients suggest that complete steroid withdrawal is possible in the majority of recipients under treatment with a cyclosporin A-rapamycin (CsA RAPA) regimen. Furthermore, preliminary studies suggest that a marked reduction in the dose of CsA may be possible under the umbrella of RAPA coverage. The gain in immunosuppressive efficacy afforded by RAPA has not only been obtained without an increased morbidity owing to infectious or neoplastic causes, but also with the potential for reducing the incidence and/or progression of chronic rejection.     

VARICELLA ZOSTER VIRUS INFECTIONS IN THE PEDIATRIC STEM CELL TRANSPLANT PATIENT

Varicella zoster virus (VZV), a member of the human herpesvirus family, causes the clinical syndromes of chickenpox during primary infection and shingles on later reactivation. In immunocompromised patients, including those undergoing hematopoietic stem cell transplantation, VZV can produce life-threatening infections. The most serious forms of VZV infection involve hematogenous dissemination of the virus to vital organs, such as the lung, brain, and liver. Advances in immunoprophylaxis, antiviral chemotherapy, and vaccine development have provided effective tools to limit the morbidity and mortality previously associated with VZV infection in hematopoietic stem cell transplant patients. In this review, we discuss virologic aspects of VZV, pathogenesis of VZV infection, methods of viral diagnosis, clinical manifestations of infection in both normal and immunocompromised patients, and available preventative and therapeutic measures.     

Génétique des schizophrénies : mise en perspective des schizophrénies à début précoce et autres pathologies du développement

Schizophrenia (SCZ) is a severe brain disorder characterized by hallucinations, delusions, flat and/or inappropriate affect and cognitive impairment. The lifetime risk is about 0.5% with heritability of 65–85%. The prevalence of early-onset schizophrenia (defined here as before 15 years of age) has not been well studied, but is likely to be 5–10% of all cases. The rarity of early-onset SCZ has made it difficult to study. We focus on genetic studies of adults with schizophrenia, highlighting results for early-onset schizophrenia where available. Prior to the past 5 years, studies failed to find replicable association or linkage between SCZ and specific genes when appropriate statistical corrections for multiple testing were used. Many false positive results were probably reported using the candidate gene approach. Recently, the development of single nucleotide polymorphism (SNP) “chips” has permitted large genome-wide association study (GWAS) analyses that suggest that across all age groups, a proportion of genetic risk can be attributed to a large number of common SNP, each with a very small effect on risk (odds ratios of 1.1 or less). The greatest known genetic effect is conferred by the 1.5–3 Mb 22q.11.2 deletions, which occurs in ∼ 1/4000–1/6000 births with SCZ developing in 20–30% of carriers. Large SNP and aCGH microarray studies have now identified associations between SCZ and other rare, large copy number variations (CNV, insertions and deletions) with high odds ratios (5–10), including deletions of 1q21, 2p16.3 (neurexin-1 gene), 3q29 and 15q13.3, and duplications of 16p11.2. Some of these CNV are also associated with autism or other developmental disorders as well as epilepsy or intellectual deficiency, suggesting some overlap in the mechanisms that contribute to risks of these disorders. Based on preliminary data from larger-scale analyses in progress, approximately 1–2% of cases carry a CNV that has been clearly associated with SCZ (ORs 4–12). Whole exome and genome sequencing studies of large adult samples will be the next steps to identify rarer SCZ-associated mutations, including point mutations and smaller as well as rarer CNV. Genetic findings are beginning to contribute to an understanding of biological mechanisms of SCZ risk and may lead to new approaches to treatment.     

INACTIVATION OF PULMONARY SURFACTANT AND THE TREATMENT OF ACUTE LUNG INJURIES

Inactivation of pulmonary surfactant may be important in acute lung injury and acute respiratory distress syndrome. Treatment of surfactant dysfunction by instilling exogenous surfactants may improve gas exchange and pulmonary mechanics. Surfactants used for treatment vary in their attributes and effects, so when various surfactants are considered for therapy, resistance to inactivation is an important consideration. Animal models of acute lung injury exist in which the relative merits of surfactants can be compared. We hypothesize that the surfactants most resistant to inactivation in vitro will be the ones that are most effective in treatment of animal models of acute lung injury. Surfactants with higher concentrations of surfactant proteins (specifically A, B, and C) are more resistant to inactivation. Nonionic polymers mimic surfactant proteins in preventing surfactant inactivation under some conditions. Adding nonionic polymers to surfactant containing minimal amounts of SP-B and SP-C markedly improves lung function of animals with lung injury. Making surfactants more "inactivation-proof" may improve surfactant therapy of acute lung injuries.     

Plasma Proinsulin and C-Peptide Concentrations in Children with Hyperinsulinaemic Hypoglycaemia

ABSTRACT. Plasma concentrations of proinsulin and C-peptide were measured in five children presenting with svere hypoglycaemia associated with elevated plasma levels of immunoreactive insulin (IRI) in order to determine whether the profile of circulating B-cell products related to the underlying pathophysiology of the pancreas. Results were compared with data from 13 normal infants. Four children, three neonates and a nine year old girl, were subjected to partial or total pancreatectomy. The neonates had nesidioblastosis, nesidioblastosis with a microadenoma, and a functional abnormality without histological derangement respectively; the older child had a localised adenoma. The remaining child, a neonate, had transient hypoglycaemia and elevated IRI levels associated with hyperlactataemia and hyperalaninae-mia. All the children had markedly elevated plasma proinsulin concentrations; the highest levels were seen in the child with an isolated adenoma and in the neonate with nesidioblastosis and a microadenoma. Both of these children also had substantially elevated plasma C-peptide concentrations. The remaining three neonates had plasma C-peptide levels, which although in the normal range for normoglycaemia were inappropriately elevated during hypoglycaemia. It is concluded that elevated proinsulin and C-peptide concentrations are seen in children with hypoglycaemia associated with increased plasma IRI levels and that the profile of the concentrations does not provide a reliable marker for the nature of the underlying pancreatic abnormality.     

Growth tracks in early childhood

Aim: Child growth is modulated by numerous factors and, particularly in infancy and early childhood, often tends to follow apparently irregular patterns, with many centiles crossed before the later growth channels are reached. The aim of this study was to visualize the diversity of individual growth. Design: The study investigated 333 girls and 329 boys without chronic illnesses from four paediatric practices in Kiel, Germany. The children were measured on natural     

Residual pulmonary hypertension in children after treatment with inhaled nitric oxide: a follow-up study regarding cardiopulmonary and neurological symptoms

Inhaled nitric oxide is a potent vasodilator in acute severe pulmonary hypertension and is increasingly used as rescue treatment in intensive care algorithms aiming at reducing severe hypoxaemia in neonates and children. Although the immediate effects may seem impressive, longterm outcome regarding residual pulmonary hypertension and other sequelae has been studied in only a very few patients. The aim of the present study was to evaluate residual pulmonary hypertension, cardiopulmonary or neurological symptoms in children after treatment with inhaled nitric oxide in severely hypoxaemic and/or pulmonary hypertensive mechanically ventilated children. The study was performed in four paediatric intensive care units in university hospitals in Sweden, Norway and Australia. Patients who had received inhaled nitric oxide as part of their intensive care treatment for severe hypoxaemia and/or pulmonary hypertension, and in whom 6 mo had elapsed since treatment, were included for evaluation. Thus 36 paediatric or neonatal patients were examined for circulatory, respiratory or neurological disorders with clinical examination, echocardiography, chest X-ray and a capillary blood sample. Four patients with congenital heart disease had residual pulmonary hypertension. Nine patients were receiving bronchodilators. Sixteen patients had minor (n = 15) or moderate (n = 1) changes on a chest X-ray. One patient had a possible delay in psychomotor development. Conclusions: In spite of the severity of their primary illness, we found that the overwhelming majority of the surviving children were asymptomatic and doing well. The few residual circulatory and respiratory symptoms could be related to the initial condition.