Polycystic kidney disease and other genetic kidney disorders

Cystic kidney diseases encompass a range of genetic disorders in which the primary cilia of the cells are affected and thereby cysts form as a result. There are an increasing range of cystic renal diseases recognized due to the advances in genomics. The most common genetic kidney condition is autosomal dominant polycystic kidney disease (ADPKD). ADPKD leads to renal failure in adulthood. In children, hypertension is common and if treated, may slow down renal decline. The most common cystic kidney disease causing renal failure in children is autosomal recessive polycystic kidney disease (ARPKD). ARPKD also affects the liver. These conditions often have extra-renal features which also need to be addressed. Until recently, treatments were mainly supportive but now it is possible to slow down development of cyst formation and renal decline in ADPKD. This raises hope for treatment for other cystic renal conditions as more genes are identified and underlying mechanisms defined.     

Polycystic kidney disease: the cilium as a common pathway in cystogenesis

PURPOSE OF REVIEW: Polycystic kidney disease (PKD) is characterized by the formation and progressive expansion of cysts in the kidney, frequently leading to renal failure. The purpose of this review is to summarize recent studies that have provided insight into the mechanisms of cytogenesis. RECENT FINDINGS: Mutations in cilia-associated proteins have been identified in a number of diseases associated with cyst formation, including autosomal dominant and recessive PKD, and nephronophthisis. The primary cilia are finger-like projections on the surface of all kidney cells, except acid-base transporting intercalated cells in the collecting duct. Cilia have been proposed to serve as mechano- or chemosensors, responding to and interacting with the microenvironment. Abnormal cilia structure or function or both may lead to abnormalities in cell proliferation and tubular differentiation, ultimately leading to cyst formation. In addition to ciliary dysfunction, other potential mechanisms of cystogenesis need to be explored. SUMMARY: Our understanding of the importance of the primary cilium in renal cyst formation may guide potential therapy for cystic kidney diseases by targeting the structural and functional integrity of the cilia.     

对慢性肾脏病概念的再认识

徐虹教授 YAP教授，您好!您作为复旦大学附属儿科医院的客座教授，连续多年的访问，每一次的学术报告和查房都给我们带来大量的、重要的信息，使我们受益匪浅。同时也要特别地祝贺您这次访问的学术讲座“慢性·肾脏病管理：ABC策略”非常精彩。[第一段]     

自噬与儿童肾脏疾病的研究进展

1962年Ashford和Porten在用胰高血糖素处理小鼠肝细胞时观察到细胞中存在"self-eating(自食)",并将这一现象命名为"autophagy(自噬)",1963年De Duve首次提出细胞自噬的生物学概念,但之后一段很长的时间里,并没有引起科学界的重视,直到近10年来,随着分子生物学技术、基因技术和自噬检测技术的飞速发展,以及在分子水平对自噬及相关分子调节机制的深入研究,自噬在儿童肾脏病的进程中所起的具体作用也在显现,选择性的激活或抑制自噬来阻止儿童肾脏疾病的进展可成为一种新的治疗手段.人们对自噬的研究取得了重大进展,特别是2005年以来,随着第一次国际性自噬领域会议的召开和一份全新的国际性杂志的诞生,自噬也越来越受到关注,并逐渐成为当前生物医学领域新的研究热点,其在肾脏生理和病理生理意义方面的研究刚刚起步,在肾脏疾病中的价值和意义也正在探索之中.因此,全面而深刻的理解自噬及其相关分子的调节机制,将有助于我们对肾脏病发病机制的深入研究以及为肾脏病的临床治疗打开新的思路.     

儿童慢性肾脏病

儿童慢性肾脏病(chronic kidney disease,CKD)是严重影响儿童正常生长发育的慢性进展性疾病,该病起病隐匿,部分最终进展为终末期肾病(end-stage renal disease,ESRD),需肾脏替代治疗维持生命.该文就儿童慢性肾脏病的病因、发病机制、诊断及治疗作一综述,旨在使人们更早、更全面地了解CKD,并采取积极的措施,延缓CKD的进展,防止ESRD的发生.     

慢性肾脏病儿童预防接种

1免疫接种的必要性来自成人的研究显示,感染是导致终末期肾病(ESRD)患者的第二位死亡原因,也是导致依赖透析和保守治疗的慢性肾脏病(CKD)患者住院的主要原因[1-2]。CKD患者存在免疫功能受损,成人研究显示,CKD患者T淋巴细胞活化、增殖功能受损,抗体依赖细胞介导的细胞毒作用减低,淋巴因子产生减低,B淋巴细胞数量减低,吞噬细胞功能损     

儿童慢性肾脏病管理

2006年国际肾脏病学会(international society of ne-phrology,ISN)和国际肾脏基金联合会(international federa-tion of kidney foundation,IFKF)联合倡议,将每年3月份的第2个星期四定为世界肾脏日,目的是唤起全球各界人士对慢性肾脏病(chronic kidney disease,CKD)的高度关注。目前,儿童CKD的概念也已经得到较广泛的重视。根     

吗替麦考酚酯在儿童肾脏疾病中的应用

吗替麦考酚酯是一种新型的免疫抑制剂,可选择性抑制T、B细胞增殖。临床中广泛应用于器官移植、系统性红斑狼疮等免疫性疾病和原发性肾小球疾病等的治疗。该文主要综述吗替麦考酚酯近年来在儿童肾脏疾病中的应用与疗效。     

Polycystic disease and hepatic fibrosis in children. Renal function studies.

Renal function studies were done in five children with infantile polycystic disease (IPCD)of kidneys and liver and in four with congenital hepatic fibrosis (CHF). Glomerular filtration rate was reduced in all IPCD patients and in two of four CHF patients. Urinary concentrating ability following water deprivation and vasopressin administration was impaired in all IPCD patients and in three of four CHF patients. During control period, all patients had asymptomatic metabolic acidosis with total carbon dioxide content less than or equal to 20.5 millimols/liter, and net acid excretion (NAE) was reduced in all but one. Ammonium chloride was administered to seven patients; NAE increased in all, but the increments were subnormal in four. The inability to excrete maximally concentrated urine and an adequate amount of net acid may best be explained by abnormal tubular structure or alterations in medullary architecture secondary to progressive scarring, or both.     

Body growth in children with polycystic kidney disease

We analysed the body growth of 121 prepubertal children with polycystic kidney disease participating in a longitudinal multicentre study. The patients were followed from an age of 1 to 9 years in girls and 1 to 10 years in boys over a mean period of 3.6 years. Children with end-stage renal disease were excluded. Fifty-four patients had the autosomal dominant form of the disease and 67 the autosomal recessive form. At last observation, 2% of patients with the dominant form and 28% of those with the recessive form had an estimated glomerular filtration rate of < 60 ml/(min 1.73 m²). At first observation, the mean height SD score (SDS) in patients with the dominant form was almost the same as in controls, whilst in those with the recessive form it was significantly decreased (girls –0.82 SDS, boys -0.68 SDS, p < 0.001). During the follow-up the height SDS decreased slightly in both groups (NS). In patients with autosomal recessive kidney disease the degree of growth retardation appeared to be related to renal function: at last observation the height of girls with an estimated glomerular filtration rate of < 60ml/(min 1.73 m²) was more retarded than that of boys (mean -2.1 SDS versus -1.5 SDS, NS). The height SDS and renal function at last observation correlated in girls ( r = 0.83, p < 0.001) but not in boys ( r = 0.55) with the recessive form. No correlation was found between the height SDS and hypertension. The weight-for-height SDS at onset was significantly reduced in patients with the recessive form with decreased renal function. Our data suggest that the autosomal recessive, but not the dominant, form of polycystic kidney disease is associated with early growth retardation, which seems to be more severe in girls, probably due to the more rapid deterioration of renal function.     

儿童慢性肾脏病替代治疗

儿童慢性肾脏病(chronic kidney disease,CKD)的替代治疗包括血液净化和肾脏移植,虽然肾移植是最有效的治疗方法,但由于儿童生理特点及肾源等问题,我国目前仍以透析治疗为主。1儿童慢性肾脏病替代治疗现状腹膜透析(peritoneal dialysis,PD)、血液透析(hemodial-ysis,HD)均属血液净化(blood purification)的范畴,指将患者的血液在体外通过净化装置,除去血液中某些致病物质,达到净化血液目的技术总称。