肾移植后的肺结核

背景:肾移植后患者肺结核发病率显著高于正常人群,临床表现不典型,给诊断和治疗带来困难。目的:总结肾移植后肺结核感染的流行病学、临床表现、早期诊断、治疗及预防措施。方法:以"肾移植,肺结核,诊断,治疗,预防"为中文检索词,以"renal transplantation,tuberculosis,diagnosis,therapy,precautionary"为英文检索词,检索中国知网(CNKI)期刊全文数据库、Medline和外文生物医学期刊全文数据库(Foreign Journals Integration System)2001-01/2009-12有关肾移植后肺结核的文章,纳入有关肾移植后肺结核的临床治疗的文献。排除重复性研究和不典型报道。保留39篇文献做进一步分析。结果与结论:肾移植后患者肺结核的诊断需借助胸部X射线、痰涂片或培养、PPD、血Anti-TBAb及PCR等综合检测,结合临床表现是早期诊断的关键。遇临床表现可疑者可行经验性抗结核治疗,一旦确诊调整免疫抑制方案,增加糖皮质激素用量,果断采取抗结核治疗以及营养支持治疗,将有助改善患者的预后。采用适合国人的免疫抑制方案,对高危人群给以预防性化疗或可起到预防作用。     

骨髓源性干细胞移植对马兜铃酸肾病大鼠尿酶与尿微球蛋白排泄的影响

目的观察骨髓源性干细胞移植对慢性马兜铃酸肾病(CAAN)大鼠肾小管功能损害的干预作用。方法制作慢性马兜铃酸肾病大鼠模型,随机分为治疗组和非治疗组,治疗组予以经尾静脉注射同系雄性大鼠骨髓干细胞;非治疗组予以尾静脉注射等量生理盐水;另设正常对照组。各组每周测量体重,并分别于尾静脉注射干细胞或生理盐水后第30d留尿,测24h尿量、用酶-底物直接显色法检测尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)量和用放射免疫法检测尿微球蛋白(β2-MG)。结果治疗组尿NAG含量及尿β2-MG排泄量较非治疗组明显减少,差异显著(P<0.05),但仍高于正常组(P<0.05)。骨髓干细胞移植能减少慢性马兜铃酸肾病大鼠尿NAG酶和尿β2-MG的排泄量。结论骨髓干细胞移植对慢性马兜铃酸肾病肾小管功能损害有一定的恢复作用。     

尿脱落细胞荧光原位杂交检测对尿路上皮癌的诊断价值及漏诊原因分析

目的 研究荧光原位杂交(FISH)检测尿脱落细胞9p21和3、7、17号染色体数目变化,协助尿路上皮癌诊断和术后监测的特异度和敏感度,并分析和研究造成漏诊的原因.方法 检测尿脱落细胞染色体数目变化,并做病理活检;以病理检查结果为金标准评价该检测的特异度和敏感度.漏诊病例的癌组织行FISH检测,并复查尿脱落细胞滴片,分析漏诊原因.结果 100例样本中,35例尿路上皮癌中28例FISH阳性,敏感度为80%;65例非肿瘤中65例FISH阴性,特异度为100%.28例高级别尿路上皮癌3例漏诊,敏感度为89.29%,其癌组织均存在与尿路上皮癌相关的非整倍体,其滴片中尿脱落细胞均少但均未见存在与尿路上皮癌相关的非整倍体.7例低级别尿路上皮癌4例漏诊,敏感度为42.86%,其中2例癌组织仅少量癌细胞存在与尿路上皮癌相关的非整倍体,2例未见上述异常;其滴片中尿脱落细胞2例细胞数少但均未见与尿路上皮癌相关的非整倍体.结论 用FISH检测尿脱落细胞上是否存在9p21和3、7、17号染色体与尿路上皮癌相关的非整倍体,具有较高的敏感性和特异性,可用于辅助尿路上皮癌诊断和术后监测.该检测对于高级别尿路上皮癌更敏感.自然尿中尿脱落细胞较少是导致该检测漏诊的主要原因;对于低级别尿路上皮癌,缺乏与尿路上皮癌相关的遗传学异常是导致该检测漏诊的主要原因.     

膀胱尿路上皮癌组织中miR-133b的表达水平与其化疗敏感性的关系分析

目的 探讨膀胱尿路上皮癌组织中miR-133b的表达水平与其化疗敏感性的关系分析.方法 回顾性分析2011年2月至2012年2月于本院确诊为膀胱尿路上皮癌患者65例,根据癌组织中miR-133b表达水平将其分为高表达组(n=25)和低表达组(n=40),采用茎环实时荧光逆转录聚合酶链反应(stem-loop real-time,RT-PCR)检测膀胱尿路上皮癌组织和癌旁正常组织中 mi R-133b的表达水平,随访5年,统计分析所有患者化疗效果、5年存活情况.结果 膀胱尿路上皮癌组织中miR-133b的表达量(U6标准化后的) 低于癌旁正常组织,差异有统计学意义(P<0.05);高表达组患者化疗有效率高于低表达组,差异有统计学意义(P<0.05);所有患者随访0.5~5年,平均随访时间3.86年,最终有45例存活5年以上,高表达组患者5年存活率(88.00%)高于低表达组(57.25%),差异有统计学意义(P<0.05);存活组患者膀胱尿路上皮癌组织中miR-133b水平高于死亡组,差异有统计学意义(P<0.05).结论 与癌旁正常组织比较,膀胱尿路上皮癌组织中miR-133b呈明显低表达,且与术后化疗敏感性、预后有密切关系,有可能作为预测化疗疗效和判断预后的指标之一.     

肾移植术后原肾相继发生恶性肿瘤1例

肾移植术后受者因长期服用免疫抑制剂,易患肿瘤.国内文献报道[1],肾移植术后肿瘤发生率为15.0%,显著高于普通人群.本文报道一例肾移植术后9年原右肾癌而行肾癌根治术,肾移植后11年移植肾丧失功能再次行肾移植,再次肾植术后4年原左肾发生恶生肿瘤,成功切除肿瘤并存活至今.现次诊治经过及结果报道如下.     

类胰蛋白酶阳性肥大细胞在大鼠马兜铃酸肾病模型中的分布及意义

马兜铃酸肾病(aristolochic acid nephropathy，AAN)发病机制目前尚不十分清楚，细胞免疫是否参与疾病的启动过程，国内外尚有争论。虽然一般认为，AAN为少细胞性的间质纤维化，但其病理证据来自于肾移植后的摘除肾。近年研究发现，肾间质中可见CD4^ 、CD8^ 和CD68^ 细胞浸润，并且早期应用泼尼松治疗取得了一定疗效，说明AAN的发病可能伴随炎性反应过程。     

肾移植后糖尿病：可改变与不可改变的危险因素

背景：肾移植后糖尿病是肾移植的主要并发症,了解其发生的危险因素并进行预防,可提高肾移植患者的存活率。目的：探讨肾移植后糖尿病发生的高危因素。方法：应用文献检索的方法获取肾移植后糖尿病发生危险因素的相关研究文献,对符合研究标准的文献进行深入的数据分析。对进行肾移植的患者进行空腹血糖、餐后2 h血糖、糖化血红蛋白以及肝功能、免疫抑制剂浓度谷值等各项指标的检测观察,分析肾移植后糖尿病的发生是否与患者性别、年龄、体质量指数、糖尿病家族史、肾移植后糖尿病起病时间、肝功能以及免疫抑制剂和激素的应用等因素有关。结果与结论：研究结果显示,肾移植后糖尿病患者的症状不典型,起病早,胰岛功能受损,肝功能异常。肾移植患者的年龄、体质量指数、糖尿病家族史、糖耐量异常、肝功能异常以及免疫抑制剂的应用均是肾移植后糖尿病发生的高危因素,而患者性别则与肾移植后糖尿病的发生无明显相关性。了解肾移植后糖尿病发生的高危因素有助于预防移植后糖尿病的发生,提高肾移植患者的存活率。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

CRTER关注“肾移植后并发症”内容

<正>肾移植后尿瘘肾移植后尿路并发症的发生及治疗:1223例次资料回顾肾移植10年514例术后尿瘘23例:分类及治疗同一机构9年间1203例肾移植后尿瘘处理27例     

膀胱尿路上皮癌中巨噬细胞移动抑制因子表达的临床意义

目的检测巨噬细胞移动抑制因子在膀胱尿路上皮癌中的表达及临床意义。方法采用Western bolt方法检测40对膀胱癌与手术切缘非癌组织中巨噬细胞移动抑制因子蛋白表达并分析其变化规律;再应用免疫组织化学法检测75对术后固定的膀胱癌与切缘组织中巨噬细胞移动抑制因子的表达并分析其与膀胱尿路上皮癌生物学行为的关系。结果膀胱尿路上皮癌中巨噬细胞移动抑制因子的表达与TNM分期呈正相关(P<0.05),并且在淋巴结转移阳性的膀胱尿路上皮癌中巨噬细胞移动抑制因子的表达显著高于淋巴结转移阴性患者,巨噬细胞移动抑制因子表达与膀胱尿路上皮癌患者生存期呈负相关(P=0.0341)。结论巨噬细胞移动抑制因子可能是膀胱尿路上皮癌变多阶段演进过程中的重要变化分子之一,可能成为膀胱尿路上皮癌分子诊断的生物标志。     

对比分析超声与CT诊断膀胱尿路上皮癌

目的比较超声与CT对膀胱尿路上皮癌的影像表现及诊断价值。方法选择45例膀胱尿路上皮癌患者,其中男性36例,女性9例;年龄27~83岁,平均年龄62.7岁。术前行超声和CT检查,分析其诊断结果。结果 45例膀胱尿路上皮癌中,超声检查发现43例,多表现为中等回声结节,回声较均匀,形态较规则,边缘较平滑,血液供应较丰富,超声诊断符合率为95.6%。45例膀胱尿路上皮癌行CT检查均发现病灶,多表现为膀胱壁较规则的乳头状突起,边缘较规整,36例行增强扫描均见较明显强化,CT诊断符合率为91.1%。结论超声和CT均为诊断膀胱癌的重要影像方法,而超声检查操作方便,无辐射,可作为首选检查方法。     

Aristolochic acid nephropathy: Harbinger of a global iatrogenic disease

This review constitutes an overview of our investigations of aristolochic acid nephropathy, a chronic kidney disease associated with carcinomas of the upper urinary tract. Our studies began by confirming the hypothesis that chronic dietary poisoning by aristolochic acid was responsible for endemic (Balkan) nephropathy. A unique TP53 mutational signature in urothelial tumors and the presence of aristolactam‐DNA adducts in the renal cortex, defined in the course of this research, proved to be robust biomarkers of exposure to this potent nephrotoxin and human carcinogen. Armed with this information, we used molecular epidemiologic approaches and novel mechanistic information to establish the causative role of aristolochic acid in upper urinary tract carcinoma in Taiwan, where one‐third of the population had been prescribed herbal remedies containing Aristolochia, and the recorded incidence of upper urinary tract cancers is the highest in the world. As traditional Chinese medicine is practiced similarly in Taiwan and China, it is likely that upper urinary tract carcinomas and their attendant aristolochic acid nephropathy are prevalent in China and other Asian countries where Aristolochia herbs have been used for centuries in the treatment and prevention of disease, creating a potential public health problem of considerable magnitude. Environ. Mol. Mutagen., 2013. © 2012 Wiley Periodicals, Inc.     

Evidence of exposure to aristolochic acid in patients with urothelial cancer from a Balkan endemic nephropathy region of Romania

Recently, chronic Aristolochia poisoning was found responsible for the aetiology of Balkan endemic nephropathy (BEN) in Croatia, Serbia, and Bosnia, and diet was the likely route of exposure to aristolochic acid (AA). BEN, often associated with an increased incidence of upper urinary tract carcinoma (UUC), also affects residents of certain rural villages in Romania. AA is a nephrotoxin and human carcinogen that forms DNA adducts after metabolic activation, which induce characteristic TP53 mutations in urothelial tumours. Here we present the first evidence linking AA exposure to UUC in residents of an endemic region in the Romanian Mehedinti County. DNA was extracted from kidney and tumour tissue of seven patients who underwent nephroureterectomy for UUC and resided in BEN villages (endemic group). Five patients with UUC from nonendemic villages served as controls. AA‐DNA adducts (7‐(deoxyadenosin‐N⁶‐yl)‐aristolactam I), established biomarkers of AA exposure, were identified by ³²P‐postlabelling in renal DNA of six patients from the endemic group and in one of the nonendemic group (adduct levels ranged from 0.3 to 6.5 adducts per 10⁸ nucleotides). Additionally, an A to T transversion in TP53, a base substitution characteristic of AA mutagenic activity was found in urothelial tumour DNA of one patient from the endemic group. Our results provide a molecular link to the cause of urothelial tumours in BEN regions of Romania indicating that AA is the common aetiological agent for BEN across its numerous geographical foci. Environ. Mol. Mutagen., 2012. © 2012 Wiley Periodicals, Inc.     

Urothelial carcinoma associated with Balkan endemic nephropathy. A worldwide disease

Balkan endemic nephropathy (BEN), a familial chronic tubulo-interstitial disease with a slow progression to terminal renal failure, affects people living in the alluvial plains along the tributaries of the Danube River. One of its most peculiar characteristics is a strong association with upper urothelial cancer. An increased incidence of upper urinary tract (UUT) transitional cell cancer (TCC) was discovered among the inhabitants of endemic settlements and in families affected by BEN. In areas where BEN is endemic, the incidence of upper tract TCC is significantly higher, even 100 times, than in non-endemic regions. A high incidence of urothelial cancer in end-stage BEN patients strongly suggests preventive nephro-ureterectomy in all end-stage patients with BEN treated with either transplantation or dialysis. Better understanding of the molecular mechanisms involved in carcinogenesis and tumor progression, has provided a large number of molecular markers of TCC, with a potential diagnostic and prognostic value. Markers that distinguish among TCC, normal urothelium, and benign urothelial conditions are potentially diagnostic, prognostic, and therapeutic targets. The geographic correlation and presence of AA-DNA adducts in both BEN and associated urothelial cancer, support the speculation that these diseases share a common etiology. Dietary exposure to AA is a significant risk factor for BEN and its attendant transitional cell cancer. These are cases of well-known AA induced urothelial carcinoma, and could be detected worldwide. The presence of more than one risk factors is possible and it is important to test etiological hypotheses in different endemic foci, preferably as a multicentric research.     

Aristolochic acid as a probable human cancer hazard in herbal remedies: a review

The old herbal drug aristolochic acid (AA), derived from Aristolochia spp., has been associated with the development of a novel nephropathy, designated aristolochic acid nephropathy (AAN), and urothelial cancer in AAN patients. There is clear evidence that the major components of the plant extract AA, aristolochic acid I (AAI) and aristolochic acid II (AAII), both nitrophenanthrene carboxylic acids, are genotoxic mutagens forming DNA adducts after metabolic activation through simple reduction of the nitro group. Several mammalian enzymes have been shown to be capable of activating both AAI and AAII in vitro and in cells. The activating metabolism has been elucidated and is consistent with the formation of a cyclic nitrenium ion with delocalized charge leading to the preferential formation of purine adducts bound to the exocyclic amino groups of deoxyadenosine and deoxyguanosine. The predominant DNA adduct in vivo, 7-(deoxyadenosin-N(6)-yl)aristolactam I (dA-AAI), which is the most persistent of the adducts in target tissue, is a mutagenic lesion leading to AT-->TA transversions in vitro. This transversion mutation is found at high frequency in codon 61 of the H-ras oncogene in tumours of rodents induced by AAI, suggesting that dA-AAI might be the critical lesion in the carcinogenic process in rodents. DNA-binding studies confirmed that both AAs bind to the adenines of codon 61 in the H-ras mouse gene and preferentially to purines in the human p53 gene. In contrast, the molecular mechanism of renal interstitial fibrosis in humans after chronic administration of AA remains to be explored. However, preliminary findings suggest that DNA damage by AA is not only responsible for the tumour development but also for the destructive fibrotic process in the kidney. It is concluded that there is significant evidence that AA is a powerful nephrotoxic and carcinogenic substance with an extremely short latency period, not only in animals but also in humans. In particular, the highly similar metabolic pathway of activation and resultant DNA adducts of AA allows the extrapolation of carcinogenesis data from laboratory animals to the human situation. Therefore, all products containing botanicals known to or suspected of containing AA should be banned from the market world wide.     

Collecting duct carcinoma of the kidney: an immunohistochemical evaluation of the use of antibodies for differential diagnosis

Collecting duct carcinoma is a highly aggressive renal epithelial malignancy, although it accounts for less than 1% of the incidence of renal epithelial neoplasms. Differential diagnoses between collecting duct carcinoma, pelvic urothelial carcinoma with marked invasion to the renal parenchyma (invasive urothelial carcinoma), and papillary renal cell carcinoma is often challenging. In our current study, we examined the utility of using commercially available antibodies, in conjunction with lectin histochemistry, for such differential diagnoses. We examined 17 cases of collecting duct carcinoma, 10 cases of invasive urothelial carcinoma and 15 cases of papillary renal cell carcinoma (type 1, 6 cases; type 2, 9 cases) in these evaluations. Our results indicated that Ulex europaeus agglutinin 1, E-cadherin, and c-KIT were frequently positive in collecting duct carcinoma and invasive urothelial carcinoma, in comparison with papillary renal cell carcinoma, which had negative results for CD10 and α-methylacyl CoA racemase. We found, however, that collecting duct carcinoma showed positivity for high-molecular-weight cytokeratin and low-molecular-weight cytokeratin at a low frequency compared with invasive urothelial carcinoma, and that these distinctions need further careful evaluation. In addition, high-molecular-weight cytokeratin positivity was not a reliable marker for collecting duct carcinoma. We conclude that Ulex europaeus agglutinin 1 reactivity and positivity for E-cadherin and c-KIT are effective in distinguishing collecting duct carcinoma from papillary renal cell carcinoma, and that negative results for α-methylacyl CoA racemase and CD10 are potentially useful hallmarks of this distinction also. In contrast, a differential diagnosis for collecting duct carcinoma and invasive urothelial carcinoma will require careful examination of multiple routinely stained specimens, particularly in cases of in situ neoplastic lesions in the pelvic mucosa.     

Unsuspected analgesic nephropathy in transitional cell carcinoma of the upper tract: a morphological study

Analgesic nephropathy is known to have a high incidence in Australia where, following the experience in Scandinavia, reports have been published for some time recording the association between analgesic nephropathy and urothelial malignancies. The morbid anatomical features of analgesic nephropathy are now sufficiently well accepted to allow a retrospective study of unselected nephrectomies for transitional cell carcinoma of the renal pelvis and ureter, in order to assess the incidence of analgesic-type changes in this well defined group of malignancies. The records of a large general histopathology department between 1972–1978 were searched and 24 consecutive transitional cell carcinomas in these sites treated by nephrectomy were selected for study. Of these, 21 were suitable for assessment and on review were shown to comprise 11 cases with papillary changes acceptable as analgesic in type and five which were suggestive of early analgesic change. Of these 16, seven were female, only two were known analgesic abusers and five were recorded as consuming analgesics on a regular basis. These findings suggest that analgesics may play a significant role in the pathogenesis of urothelial malignancy in the general population.     

The human carcinogen aristolochic acid i is activated to form DNA adducts by human NAD(P)H:quinone oxidoreductase without the contribution of acetyltransferases or sulfotransferases

Ingestion of aristolochic acid (AA) is associated with development of urothelial tumors linked with AA nephropathy and is implicated in the development of Balkan endemic nephropathy-associated urothelial tumors. We investigated the efficiency of human NAD(P)H:quinone oxidoreductase (NQO1) to activate aristolochic acid I (AAI) and used in silico docking, using soft-soft (flexible) docking procedure, to study the interactions of AAI with the active site of human NQO1. AAI binds to the active site of NQO1 indicating that the binding orientation allows for direct hydride transfer (i.e., two electron reductions) to the nitro group of AAI. NQO1 activated AAI, generating DNA adduct patterns reproducing those found in urothelial tissues from humans exposed to AA. Because reduced aromatic nitro-compounds are often further activated by sulfotransferases (SULTs) or N,O-acetlytransferases (NATs), their roles in AAI activation were investigated. Our results indicate that phase II reactions do not play a major role in AAI bioactivation; neither native enzymes present in human hepatic or renal cytosols nor human SULT1A1, -1A2, -1A3, -1E, or -2A nor NAT1 or NAT2 further enhanced DNA adduct formation by AAI. Instead under the in vitro conditions used, DNA adducts arise by enzymatic reduction of AAI through the formation of a cyclic hydroxamic acid (N-hydroxyaristolactam I) favored by the carboxy group in peri position to the nitro group without additional conjugation. These results emphasize the major importance of NQO1 in the metabolic activation of AAI and provide the first evidence that initial nitroreduction is the rate limiting step in AAI activation.     

肾间质纤维化动物模型的制作和研究进展

肾间质纤维化与肾功能的恶化密切相关。动物模型实验是研究肾间质纤维化必不可少的手段,实验者应根据不同的实验目的选择适当的动物模型。本文对常见的肾间质纤维化动物模型,包括单侧输尿管梗阻、环孢素A肾病、慢性马兜铃酸肾病等8种模型的制作和研究进展作一综述。