Angiotensin-converting enzyme activity and the ACE Alu polymorphism in autosomal dominant polycystic kidney disease.

BACKGROUND: Previous studies concerning Alu I/D polymorphism in the ACE gene and ADPKD severity have used the Alu genotypes as a representative of the true biological variable, namely ACE activity. However, wide individual and ethnic differences in the proportion of variance in ACE activity explained by the I/D genotype may have confounded these studies. This investigation examines the association between ADPKD severity and ACE in terms of plasma enzyme activity and I/D genotypes in individuals from three different countries. METHODS: Blood samples were collected from 307 ADPKD patients (116 Australian, 124 Bulgarian and 67 Polish) for determination of ACE activity levels and I/D genotypes. Chronic renal failure (CRF) was present in 117 patients and end-stage renal failure (ESRF) in 68 patients. RESULTS: ACE activity was related to the I/D genotype, showing a dosage effect of the D allele (P=0.006). The proportion of variance due to the Alu polymorphism was 14%. No difference in ACE activity and I/D genotype distribution was found between patients with CRF versus normal renal function (P=0.494; P=0.576) or between those with ESRF versus those without ESRF (P=0.872; P=0.825). No effect of the I/D genotype on age at development and progression to renal failure (CRF; ESRF) was detected in the overall group, and in subgroups based on ethnic origin, linkage status and sex. CONCLUSION: ACE is not likely to play a role as a determinant of ADPKD phenotype severity.     

常染色体显性遗传多囊肾病患者外周血淋巴细胞DNA的损伤

目的 研究常染色体显性遗传多囊肾病( ADPKD)患者及其家系成员外周血淋巴细胞DNA的损伤及辐射对其基因稳定性的影响.方法 采用单细胞凝胶电泳技术( SCGE)研究10例ADPKD(A组)、1个ADPKD家系中3例无症状者(B组)、20例健康对照者(C组)外周血淋巴细胞的DNA损伤及在0.5 Gy照射后的DNA损伤情况.采用彗星分析软件(CASP)进行图像分析,以尾DNA含量(TDNA％)评价淋巴细胞的DNA损伤程度.结果 A组照射前、后TDNA％ (8.85％±0.14％,14.84％±0.77％)及照射后TDNA％的增加值(6.00％±0.77％)均显著高于C组(7.50％±0.37％,12.46％±0.26％,4.96％±0.44％),B、C两组及A、B两组间差异无统计学意义.B组中1例TDNA％照射前后均显著高于C组.结论 ADPKD患者外周血淋巴细胞具有基因不稳定性,在环境因素刺激下,有可能通过基因突变启动多脏器囊肿形成.SCGE为进一步阐明ADPKD发病机制及预后判断提供了一种新的方法和思路.     

Laparoscopic nephrectomy for autosomal dominant polycystic kidney disease

Background The authors reviewed their experience with laparoscopic nephrectomy for autosomal dominant polycystic kidney disease to evaluate whether patient-related or surgery-related factors influence operative outcomes.Methods A retrospective review was carried out of 22 consecutive laparoscopic nephrectomies performed by one surgeon in a university setting between March 1998 and March 2003. The impact of patient factors (body mass index, preoperative hemoglobin level, preoperative blood urea nitrogen and creatinine, kidney size and side, prior abdominal surgery, dialysis) and surgical factors (surgeon experience and preoperative embolization) on short-term outcomes (estimated blood loss, transfusion requirements, operative time, conversion, intra- and postoperative complications and length of stay) was analyzed using the Students t-test, Pearson correlation, and Mann–Whitney and Fisher tests.Results A total of 19 patients underwent 22 nephrectomies. The average patient age was 49 years (range, 36–65 years) and the average body mass index was 31.4 kg/m² (range, 20.4–64.5 kg/m²). Fourteen patients (68%) were receiving dialysis. Fifteen right (68%) and 7 left (32%) nephrectomies were performed. The median kidney size was 22 cm (range, 8–50 cm). Five patients (23%) had preoperative embolization. The median operative time was 255 min (range, 95–415 min). There were no mortalities. The intraoperative complication rate was 18% (1 vena cava laceration, 1 cecal perforation, 1 dialysis fistula thrombosis, 1 intrarenal bleeding requiring conversion), and the postoperative complication rate was 32% (1 myocardial infarction, 1 urgent laparotomy for clinical peritonitis, 1 minor bile fistula, 1 AV fistula thrombosis, 2 incisional hernias, 1 urinary retention). Four procedures (18%) were converted (1 for vena cava laceration, 1 for cecal perforation, 1 for intrarenal bleeding, 1 for adhesions). The median blood loss was 400 ml (range, 100–5000 ml). Eight patients (36%) received transfusions (median, 2 units). The median length of stay was 4 days. The patients who required blood transfusions had lower preoperative hemoglobin levels. Preoperative embolization did not affect surgical outcome. However, surgeon experience significantly reduced operative time.Conclusions Laparoscopic nephrectomy for autosomal dominant polycystic kidney disease is a safe procedure, providing patients with a short hospital stay. Complication and conversion rates are relatively high.Presented at the 11th International Congress of the European Association for Endoscopic Surgery and other Interventional Techniques (EAES), Glasgow, 15–18 June 2003     

271例常染色体显性遗传性多囊肾病患者临床分析

目的了解常染色体显性多囊肾病(ADPKD)患者临床特点、治疗情况及疗效。方法回顾性分析271例ADPKD患者临床资料。根据MDRD公式[GFR(ml/min)=170×血肌酐(mg/dl)-0.99×(年龄/0.357)-0.176×血尿素氮(mg/dl)-0.170×血白蛋白(g/dl)-0.318S×0.762(女性)]计算GFR。根据公式[单侧肾脏体积(mm3)=(4π/3)×(宽/4+厚/4)2×(长/2)]计算肾体积。作肾脏体积与肾功能、血压、血尿及蛋白尿之间的相关分析。结果271例患者中,男性149例,女性122例,157例(55.7%)有家族史,114例(42.1%)伴腰腹痛,肝囊肿95例(35.1%),颅内动脉瘤1例(0.37%),其他肾外囊肿10例(3.7%),严重心、脑并发症30例(11.1%)。193例(71.2%)出现血尿,血尿发生与肾脏体积关系密切,单纯卧床休息与卧床休息加止血药物治疗比较,疗效无显著差异。174例(64.2%)出现高血压,其中61.5%的患者需联合使用2种以上降压药物,治疗后收缩压(135.7±16.5)mmHg,舒张压(84.7±11.2)mmHg,显著低于治疗前。105例(38.7%)患者有蛋白尿,定量(1.48±0.80)g/24h,降压治疗后尿蛋白显著减少。肾脏体积与尿蛋白、血压呈正相关,与GFR呈负相关。76例(28.0%)出现1次或多次泌尿系感染。40例(14.8%)有泌尿系结石。结论ADPKD临床表现复杂多样,存在性别、年龄差异。肉眼血尿治疗中卧床休息十分     

Screening for intracranial aneurysms in autosomal dominant polycystic kidney disease

SUMMARY:   Screening patients with autosomal dominant polycystic kidney disease (ADPKD) for asymptomatic intracranial aneurysms has been proposed as a method of reducing the morbidity and mortality associated with aneurysm rupture. However, recent studies have shown lower spontaneous rupture rates of small aneurysms and higher risks of significant complications with interventions than previously reported. Risk-benefit analysis has not demonstrated any benefit of screening ADPKD patients without a history of subarachnoid haemorrhage (SAH) for intracranial aneurysms, and has suggested that screening might cause harm.     

Role and mechanism of C3a-C3a receptor in autosomal dominant polycystic kidney disease

Objective To explore the role and mechanism of C3a-C3a receptor (C3aR) in the progression of autosomal dominant polycystic kidney disease (ADPKD). Methods Renal tissues of ADPKD patients and PKD1 knockout mice were collected. Then the expression of C3a-C3aR, Ki67 and F4/80 in renal tissues was observed. Macrophages were stimulated with lipopolysaccharide (LPS) and interleukin 4 respectively. The expression of C3aR, TNF-α, typing markers and related signal pathway proteins was detected in each group. PKD1 knockout mice were treated with C3aR inhibitor SB290157 (1 mg/kg). Renal pathology, cyst-related indicators and renal function were observed. Results The expression of C3a and C3aR in ADPKD was up-regulated (both P＜0.05); C3aR and F4/80 were co-located in the kidney of polycystic kidney disease (PKD) mice, indicating that C3aR was mainly expressed on membrane of macrophages. In vitro, the expression of C3aR was up-regulated in M1 macrophages (P＜0.05). After the stimulation of C3a, the expression of iNOS, TNF-α and IL-6 mRNA in M1 macrophages were up-regulated (all P＜0.05), as well as the secretion of TNF-α, indicating that C3a not only affected the expression of inflammatory factors of M1 macrophages, but also affected the inflammatory microenvironment. In addition, C3a significantly activated Akt in M1 macrophages (P＜0.05). Compared with the control group, the treatment group showed a decrease in C3a-C3aR as well as serum BUN, Scr, cyst index, and two kidneys weight/body weight (2KW/BW) (all P＜0.05), and ADPKD related pathway protein expression such as p-ERK and p-P65 was significantly down-regulated (all P＜0.05). Conclusions The increased C3a in polycystic kidney tissue causes infiltration and activation of macrophages through C3aR, and then promotes ADPKD progression. The mechanism may be mediated by Akt activation and increased TNF-α production. C3aR antagonist is a potential research direction in the treatment of ADPKD.     

腹腔镜和开放去顶减压术治疗多囊肾的临床效果比较

目的:探讨腹腔镜去顶减压术治疗常染色体显性遗传性多囊肾(ADPKD)的临床价值。方法:开放手术68例,分期行双肾去顶减压术;腹腔镜手术54例,一期行双肾去顶减压术。观察两组患者在囊肿处理的数量以及手术效果方面的差异。结果:开放手术组单侧肾脏囊肿处理数量为(268±93)个,术后平均住院7.9d;腹腔镜手术组单侧肾脏囊肿处理数量(197±76)个,术后平均住院5.1d。开放手术组1例发生切口感染,腹腔镜手术组1例发生尿外渗。术后两组患者疼痛明显改善,部分患者的高血压缓解,肾功能无明显变化。随访3年患者疼痛与高血压有复发。组间比较显示,两组患者的治疗效果差异无显著性(P>0.05)。结论:腹腔镜去顶减压术手术创伤小并取得了与开放手术相同的治疗效果。     

Expression of secreted frizzled related protein 4 and effect of induced-apoptosis in autosomal dominant polycystic kidney disease

Objective To evaluate the expression of secreted frizzled related protein 4 (sFRP4) in autosomal dominant polycystic kidney disease(ADPKD) and the effect of sFRP4 induced apoptosis in ADPKD. Methods (1)Serological method: serum samples of 12 healthy people and 20 ADPKD patients were collected and the levels of sFRP4 in serum were detected by ELSIA assay. (2)Tissue experiments: normal renal tissue was collected from radical nephrectomy for renal carcinoma; polycystic renal tissues were taken from ADPKD patients. The expression of sFRP4 in renal tissues was observed by immunohistochemistry; Real-time PCR was used to explore the mRNA level of sFRP4 and caspase-3; TUNEL method was applied to observe the apoptosis cells existing in ADPKD. (3)studies in vitro: HEK-293T cells were transfected with PcDNA6 and Flag. sFRP4.PcDNA6 respectively, after which Western blotting was performed to detect the expression of caspase-3 protein and flow cytometry was performed to estimate cell apoptosis rate. Results (1)ELISA results showed serum concentrations of sFRP4 in ADPKD were markedly higher than normal control (P＜0.05). (2)Compared with normal renal tissues, the sFRP4 expression was dramatically increased in ADPKD and mainly distributed in the cytoplasm of renal tubular epithelial cells. (3)Real-time PCR showed the expression of sFRP4 and Caspase-3 mRNA in ADPKD were up-regulated comparing with those in normal control (P＜0.05). (4)TUNEL assays revealed that elevated apoptosis appeared in tubular epithelial cells of ADPKD. (5)The level of caspase-3 protein and apoptosis rate were significantly increased after over-expressed sFRP4 in HEK-293T cells (all P＜0.05). Conclusions The expression of sFRP4 is strikingly up-regulated in ADPKD. In addition, abnormal apoptosis of tubular epithelial cells exists in ADPKD and over-expressed sFRP4 can induce apoptosis of HEK-293T cells. This phenomenon may be attributed to the elevated sFRP4.     

血管紧张素转换酶基因多态性与终末期肾病

本文综述了血管张素转换酶基因及其基因多态性与终末期肾病的发生、发展及血管紧张素转换酶抑制剂肾保护作用的相关性。     

血管紧张素转换酶基因多态性与终末期肾病

本文综述了血管张素转换酶基因及其基因多态性与终末期肾病的发生、发展及血管紧张素转换酶抑制剂肾保护作用的相关性     

常染色体显性遗传性多囊肾病263例患者的临床特点

目的:分析常染色体显性遗传性多囊肾病(ADPKD)患者的临床特点。方法:回顾性分析2008年8月至2018年8月收治的263例成人型ADPKD患者的临床资料,包括性别、年龄、是否合并多囊肝、泌尿系结石、泌尿系感染;有无血尿、蛋白尿;有无糖尿病、高血压病、冠心病;血脂状况等。结果:高血压[60.1%(158/263)]、...     

常染色体显性遗传多囊肾治疗的研究进展

常染色体显性遗传多囊肾 (ADPKD)是人类目前最常见的威胁生命的单基因疾病 ,而且已成为引起人类终末期肾病的第三大疾病 ,近年人们对ADPKD发展的分子基因学和细胞病理生理学机制的认识有了很大提高 ,在此基础上人们在治疗ADPKD的研究中取得了一定进展     

改良聚合酶链反应法快速诊断常染色体显性遗传型多囊肾病

目的：检测微小卫星体ＳＭ７快速诊断常染色体显性遗传型多囊肾病（ＡＤＰＫＤ）。方法应用改良二温式聚合酶链反应（ＰＣＲ）法扩增与ＰＫＤ１位点紧密连锁的微小卫星体ＳＭ７,并对１０个家系进行基因连锁分析。结果在１０个家系１０３个家庭成员中,２９例先证者,９例无症状者通过基因连锁分析得到确诊,结论改良二温式ＰＣＲ法检测微小卫星体ＳＭ７可早期快速诊断ＡＤＰＫＤ。     

常染色体显性遗传多囊肾治疗的研究进展

常染色体显性遗传多囊肾（ADPKD）是人类目前最常见的威胁生命的单基因疾病，而且已成为引起人类终末期肾病的第三大疾病，近年人们对ADPKD发展的分子基因学和细胞病理生理学机制的认识有了很大提高，在此基础上人们在治疗ADPKD的研究中取得了一定进展。     

肾细胞凋亡与常染色体显性遗传性多囊肾病肾组织缺失的相关研究

目的 研究肾细胞凋亡与常染色体显性遗传性多囊肾病（ADPKD）肾组织进行性缺失的关系。方法 采用琼脂糖凝胶电泳、电镜和原位末端标记（TUNEL）法、Hoechst 33342染色法测定正常肾组织、ADPKD肾组织和体外培养的ADPKD囊肿衬里上皮细胞中凋亡DNA片段。对Tunel法结果作定量分析,计算机图象分析ADPKD肾脏CT检查中残余肾组织/囊肿组织截而积比值,与肾功能衰竭程度作相关分析。结果 无或有肾功能衰竭的ADPKD肾组织中肾小球、肾小管上皮和囊肿衬里上皮细胞、体外培养的ADPKD囊肿衬里上皮细胞均发生凋亡。正常肾组织中无细胞凋亡。ADPKD肾组织中平均每10个高倍视野凋亡的肾细胞计数,肾功能正常组（A组,3.60±1.22）与氮质血症期组（B组,8.17±1.56）、终末期肾衰组（C组,17.81±3.15）间比较差异有非常显著性意义（P<0.01）。ADPKD肾组织中凋亡肾细胞数与肾功能衰竭程度显著相关（r=0.95,P<0.01）。ADPKD残余肾组织/囊肿组织截面积比值,A组（2.04±0.32）与B组（0.91±0.03）、C组（0.37±0.09）间比较差异有非常显著性意义（P<0.01）。ADPKD肾功能分期相同组中凋亡肾细胞数与残余肾组织/囊肿组织截面积比值呈负相关（r=-0.90,P<0.05）。ADPKD残余肾组织/囊肿组织截面积比值与肾功能衰竭程度呈负相关（r=-0.80,     

血管紧张素转换酶2与肾脏疾病关系研究进展

血管紧张素转换酶2(angiotensin-converting enzyme2,ACE2)是近年发现的血管紧张素转换酶的一种同系物,并且具有对抗ACE的功能.本文就ACE2和肾脏疾病关系的最新研究进展进行.