Pre-transplant treatment of large polycystic kidney

AIM: To evaluate the indications, optimal timing and outcomes of native nephrectomy and other techniques in pretransplant treatment of autosomal dominant polycystic kidney disease (PKD). METHODS: A literature review was conducted using the PubMed and Epistemonikos databases. Keywords for pre-transplant surgical management of polycystic kidneys were: Transplant, treatment and PKD. Keywords for pre-treatment embolization of PKD were: Embolization, transplant and polycystic kidney disease. The inclusion criterions were all articles found using this search method. The exclusion criterions were articles found to include bias and not attending pre-transplant treatment options. Fifteen articles were included in our final analysis. Ten articles were found regarding embolization of PKD of which three reviews were selected for final analysis. The reviews were divided into pre transplant and intra transplant treatment for the surgical treatment of PKD. All articles meeting inclusion criteria were thoroughly analyzed by two independent reviewers. A third independent reviewer was consulted if the reviewers did not agree upon the inclusion or exclusion of a specific article. No statistical analysis was performed. RESULTS: Studies vary regarding the technique used (open or laparoscopic), laterality (single or bilateral) and temporality of nephrectomy with respect to renal transplant (pre-transplant or simultaneous to transplant). Several groups argue in favor of simultaneous nephrectomy and kidney transplant since it avoids the deleterious effects of being anefric. Long-term results and patient satisfaction are acceptable. However, it is associated with increased operative time, transfusion rate, morbidity and length of hospital stay. Based on small sample studies, bilateral nephrectomy prior to transplant has been associated with a higher risk of morbidity and mortality. Studies on laparoscopic approach report it as a feasible and safe alternative to the open surgery approach, highlighting its lower complication rate, transfusions and shorter hospital stay. Arterial embolization of the kidney appears as an effective and low morbid alternative for the management of large native kidneys. The reduction in renal size allow transplant in a significant number of patients, which makes it an appealing alternative to surgery. CONCLUSION: There is limited evidence regarding best pretrasnplant treatment of large PKD but to date embolization seems an appealing alternative to augment space for renal graft allocation.     

Role of calcium in polycystic kidney disease: From signaling to pathology

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited monogenic kidney disease. Characterized by the development and growth of cysts that cause progressive kidney enlargement, it ultimately leads to end-stage renal disease. Approximately 85% of ADPKD cases are caused by mutations in the PKD1 gene, while mutations in the PKD2 gene account for the remaining 15% of cases. The PKD1 gene encodes for polycystin-1 (PC1), a large multi-functional membrane receptor protein able to regulate ion channel complexes, whereas polycystin-2 (PC2), encoded by the PKD2 gene, is an integral membrane protein that functions as a calcium-permeable cation channel, located mainly in the endoplasmic reticulum (ER). In the primary cilia of the epithelial cells, PC1 interacts with PC2 to form a polycystin complex that acts as a mechanosensor, regulating signaling pathways involved in the differentiation of kidney tubular epithelial cells. Despite progress in understanding the function of these proteins, the molecular mechanisms associated with the pathogenesis of ADPKD remain unclear. In this review we discuss how an imbalance between functional PC1 and PC2 proteins may disrupt calcium channel activities in the cilium, plasma membrane and ER, thereby altering intracellular calcium signaling and leading to the aberrant cell proliferation and apoptosis associated with the development and growth of renal cysts. Research in this field could lead to the discovery of new molecules able to rebalance intracellular calcium, thereby normalizing cell proliferation and reducing kidney cyst progression.     

TLR9和NF-κB在尖锐湿疣组织中的表达

 目的 探讨尖锐湿疣(CA)组织中Toll样受体9（TLR9）和核因子κB(NF-κB)的表达及意义。方法采用免疫组化SP法检测TLR9和NF-κB在50例CA组织和20例正常包皮组织中的表达情况，并进行比较。采用Spearman分析检测CA组织中TLR9和NF-κB表达的相关性。结果50例CA患者组织中，TLR9和NF-κB的阳性表达率分别为94.00%（47/50）和98.00%（49/50），表达强度多为+ +～+ + +。20例正常包皮组织中，TLR9和NF-κB的阳性表达率分别为10.00%（2/20）和20.00%（4/20），表达强度多为-～+。两组TLR9和NF-κB的阳性表达率和阳性表达强度差异均有统计学意义（均P<0.05）。CA组织中TLR9和NF-κB的表达呈正相关（r=0.57，P<0.05）。结论CA组织中存在TLR9和NF-κB的过表达，可能与人乳头瘤病毒感染后被过度激活有关。二者可能对CA的发生、发展有一定作用。     

1400W reduces ischemia reperfusion injury in an ex-vivo porcine model of the donation after circulatory death kidney donor

AIM: To investigate the effects of 1400W-a selective inducible nitric oxide synthase (iNOS) inhibitor in a model of donation after circulatory death (DCD) kidneys. METHODS: Porcine kidneys were retrieved after 25 min warm ischemia. They were then stored on ice for 18 h before being reperfused ex vivo with oxygenated autologous blood on an isolated organ perfusion system. The selective iNOS inhibitor 1400W (10 mg/kg) was administered before reperfusion (n = 6) vs control group (n = 7). Creatinine (1000 μmol/L) was added to the system, renal and tubular cell function and the level of ischemia reperfusion injury were assessed over 3 h of reperfusion using plasma, urine and tissue samples. RESULTS: Kidneys treated with 1400W had a higher level of creatinine clearance (CrCl) [area under the curve (AUC) CrCl: 2.37 ± 0.97 mL/min per 100 g vs 0.96 ± 0.32 mL/min per 100 g, P = 0.004] and urine output [Total: 320 ± 96 mL vs 156 ± 82 mL, P = 0.008]. There was no significant difference in levels of fractional excretion of sodium (AUC, Fr ex Na+: Control, 186.3% ± 81.7%.h vs 1400W, 153.4% ± 12.1%.h, P = 0.429). Levels of total protein creatinine ratio were significantly lower in the 1400W group after 1 h of reperfusion (1h Pr/Cr: 1400W 9068 ± 6910 mg/L/mmol/L vs Control 21586 ± 5464 mg/L/mmol/L, P = 0.026). Levels of 8-isoprostane were significantly lower in the 1400W group [8-iso/creatinine ratio: Control 239 ± 136 pg/L/mmol/L vs 1400W 139 ± 47 pg/L/mmol/L, P = 0.041]. CONCLUSION: This study demonstrated that 1400W reduced ischaemia reperfusion injury in this porcine kidney model of DCD donor. Kidneys had improved renal function and reduced oxidative stress.     

ACCESSORY MAMMARY TISSUE ASSOCIATED WITH CONGENITAL AND HEREDITARY NEPHROURINARY MALFORMATIONS

Background and Objectives. The association between polythelia (supernumerary nipple) and kidney and urinary tract malformations (KUTM) is controversial. Some authors reported this association in newborns and infants. Case-control studies dealing with adult subjects are not found in the literature. The purpose of this study is to determine the frequency of the association between accessory mammary tissue (AMT) and congenital and hereditary nephrourinary defects in an adult population compared to a control group. Methods. The study was performed in 146 white patients (123 men, 23 women) with AMT out of 2645 subjects consecutively referred to us for physical examination. The following investigations were undertaken: ultrasonographic examination of the abdomen and the kidneys, ECG, echocardiogram, roentgenogram of the vertebral column, urinalysis, and other laboratory tests. A sex- and age-matched control group without any evidence of AMT or lateral displacement of the nipples underwent the same examinations. Results. Kidney and urinary tract malformations were detected in 11 patients with AMT (nine men, two women) and in one control. These data indicate a significantly higher frequency of KUTM in the AMT-affected patients compared to controls (7.53% vs. 0.68%, P < 0.001). A broad spectrum of KUTM was discovered in association with AMT: adult dominant polycystic kidney disease, unilateral renal agenesis, cystic renal dysplasia, familial renal cysts, and congenital stenosis of the pyeloureteral joint. Conclusion. Accessory mammary tissue offers an important clue for congenital and hereditary anomalies of the kidneys and urinary collecting systems. Patients with AMT should, therefore, be extensively examined for the presence of occult nephrouropathies.     

Skin disorders in peritoneal dialysis patients: An underdiagnosed subject

AIM: To examine all skin changes in peritoneal dialysis (PD) patients followed up in our unit. METHODS: Patients on PD program for at least three months without any known chronic skin disease were included in the study. Patients with already diagnosed skin disease, those who have systemic diseases that may cause skin lesions, patients with malignancies and those who did not give informed consent were excluded from the study. All patients were examined by the same predetermined dermatologist with all findings recorded. The demographic, clinical and laboratory data including measures of dialysis adequacy of patients were recorded also. Statistical Package for Social Sciences (SPSS) for Windows 16.0 standard version was used for statistical analysis. RESULTS: Among the patients followed up in our PD unit, those without exclusion criteria who gave informed consent, 38 patients were included in the study with male/female ratio and mean age of 26/12 and 50.3 ± 13.7 years, respectively. The duration of CKD was 7.86 ± 4.16 years and the mean PD duration was 47.1 ± 29.6 mo. Primary kidney disease was diabetic nephropathy in 11, nephrosclerosis in six, uropathologies in four, chronic glomerulonephritis in three, chronic pyelonephritis in three, autosomal dominant polycystic kidney disease in three patients while cause was unknown in eight patients. All patients except for one patient had at least one skin lesion. Loss of lunula, onychomycosis and tinea pedis are the most frequent skin disorders recorded in the study group. Diabetic patients had tinea pedis more frequently (P = 0.045). No relationship of skin findings was detected with primary renal diseases, comorbidities and medications that the patients were using. CONCLUSION: Skin abnormalities are common in in PD patients. The most frequent skin pathologies are onychomycosis and tinea pedis which must not be overlooked.     

中波紫外线激活HaCaT细胞炎症信号通路的实验研究

目的 探讨中波紫外线(UVB)对角质形成细胞(KC)炎症信号通路的影响.方法 UVB(40 mJ/cm²)照射永生化人角质形成细胞株HaCaT细胞,分别于照射后0、10、30、60、120、240min收集细胞蛋白和核蛋白,蛋白质印迹法检测NF-κB信号传导通路中的重要分子-磷酸化IκB-α(P-IκB-α)、IκB-α和NF-κB p65蛋白的动态变化,以及MAPK家族的蛋白分子ERK1/2、p38、c-JNK等磷酸化激活的动态变化.结果 蛋白质印迹法检测结果显示,UVB照射后0.5h IκB-α开始发生磷酸化和降解,在第2、4小时时更加明显;细胞核蛋白p65的量在照射后0.5h开始升高,在随后的2h时达到高峰.UVB照射后10 min HaCaT细胞内的ERK1/2、p38、c-JNK蛋白的磷酸化就开始增加.结论 UVB照射KC可激活细胞内的NF-κB及MAPK信号传导通路.     

中波紫外线辐射对人表皮角质形成细胞核因子κB转录活性的影响

目的 探讨中波紫外线(UVB)辐射对表皮角质形成细胞核因子κB(NF-κB)转录活性的影响。方法 正常人表皮角质形成细胞取自健康儿童包皮,并培养于37℃、5%CO₂的培养箱中;以20、60和120 mJ/cm² UVB辐射培养细胞;分别提取UVB辐射0、2、24和48 h后角质形成细胞的全细胞蛋白、核蛋白和胞浆蛋白;免疫印迹方法检测分析全细胞蛋白和核蛋白的NF-κB/p65以及胞浆蛋白NF-κB抑制物(IκB-a)的动态变化;电泳迁移率变更分析(EMSA)方法检测分析NF-κB的转录活性。结果 UVB辐射可显著促进角质形成细胞总蛋白和核蛋白中NF-κB的蛋白表达(P<0.05),且表达量与辐射剂量成正比,UVB辐射后2 h即可有NF-κB的蛋白表达水平的升高。24 h后达高峰并持续高水平表达至48 h:不同剂量UVB辐射角质形成细胞后的不同时间,均可促进NF-κB转录活性:UVB辐射可显著抑制角质形成细胞胞浆IκB-a蛋白的表达(P<0.05)。结论 UVB辐射可显著促进角质形成细胞NF-κB的转录活性。     

抗人白介素8单克隆抗体乳膏治疗湿疹的多中心随机双盲对照研究

目的评价外用抗人白介素8单克隆抗体(抗IL-8单抗)乳膏治疗湿疹的疗效和安全性。方法随机、双盲、安慰剂对照的多中心临床研究,受试者每日外用抗IL-8单抗乳膏或乳膏基质2次,疗程3周,于治疗前及治疗后第1、2、3周各随访1次,进行疗效和安全性评价。结果4个中心共入选湿疹患者229例,纳入疗效分析209例,其中使用抗IL-8单抗乳膏治疗组104例,基质对照组105例。治疗后第1、2、3周,治疗组患者症状/体征的总计分与对照组比较均有明显下降(P<0.05～0.01)。疗程结束时,治疗组和对照组的基本痊愈率分别为27.88%、2.86%;有效率分别为56.73%、15.24%。治疗组的基本痊愈率及有效率均高于对照组(P<0.01)。两组不良反应发生率分别为4.42%和1.79%,差异无统计学意义(P=0.45),主要表现为皮损局部红斑、瘙痒加重或灼热、疼痛等,无系统不良反应。结论抗IL-8单抗乳膏治疗湿疹安全有效。     

核因子-κB反义寡核苷酸抑制紫外线诱导的HaCaT细胞反义分泌白介素6

目的 探讨核因子-κB(NF-κB)反义寡核苷酸转染体外培养的HaCaT细胞反义株HaCaT后,对紫外线(UV)诱导的HaCaT细胞反义分泌炎症因子白介素6(IL-6)的抑制作用。方法 蛋白质印迹方法测定不同剂量中波紫外线(UVB)辐射HaCaT细胞反义后NF-κBp65的变化;逆转录-聚合酶链反应测定NF-κBp65反义寡核苷酸转染后p65m RNA表达的变化;酶联免疫吸附测定法测定NF-κBp65反义寡核苷酸转染后紫外线辐射的HaCaT细胞反义分泌IL-6水平。结果 10、20、30mJ/cm² UVB辐照HaCaT细胞反义后均可显著促进NF-κBp65表达(P<0.05),不同浓度的NF-κBp65反义寡核苷酸转染后对30mJ/cm² UVB诱导的p65mRNA表达和IL-6分泌均有显著抑制作用(P<0.05)。结论 脂质体介导的NF-κBp65反义寡核苷酸转染HaCaT细胞反义,可以抑制UV辐射诱导的HaCaT细胞反义产生IL-6,表明UV诱导HaCaT细胞反义产生IL-6可能是通过UV激活NF-κBp65的表达产生的。     

毛细血管瘤组织中p63和p73基因蛋白表达的免疫组化研究

目的 探讨p63基因和p73基因蛋白与毛细血管瘤发生发展的关系。方法 采用免疫组化SP法检测40例儿童毛细血管瘤和20例正常人皮肤组织p63基因和p73基因蛋白的表达;对所获得的检测结果进行图像分析处理。结果 在正常人皮肤组、增生期与退化期血管瘤中,p63和p73蛋白的平均吸光度分别为0.923±0.191,0.953±0.120;8.271±1.953,6.408±2.151;0.920±0.187,1.073±0.516;阳性面积率分别为0.106±0.014,0.087±0.012;0.370±0.071,0.184±0.015;0.116±0.012,0.098±0.014。增生期组与退化期组、正常人皮肤组分别比较,p63和p73阳性表达的差异均有统计学意义(P<0.05),退化期组与正常人皮肤组之间,p63阳性表达的差异无统计学意义(P>0.05)。结论 p63基因在毛细血管瘤中并未作为肿瘤抑制基因起作用,相反是作为癌基因而促进内皮细胞的增殖,可能与血管形成关系密切。p73在毛细血管瘤的增生中起着重要作用。     

色素痣和恶性黑素瘤组织及A375细胞中色素上皮衍生因子的表达

目的 探讨色素上皮衍生因子(PEDF)在色素痣和恶性黑素瘤组织及A375细胞中的表达及其意义.方法 用免疫组化法检测正常人皮肤组织、正常人色素痣以及恶性黑素瘤组织中PEDF的表达与分布.用蛋白印迹法检测正常黑素细胞及恶性黑素瘤细胞株A375中PEDF的表达与分布.用RTPCR法检测正常黑素细胞及A375中PEDF mRNA的表达.结果 ①PEDF在正常皮肤组织、正常人色素痣及恶性黑素瘤组织中的表达逐渐降低,三组间差异有统计学意义(P<0.05).②PEDF在正常黑素细胞中表达,而在恶性黑素瘤细胞株缺失.③PEDF mRNA在恶性黑素瘤细胞中的表达量明显低于正常黑素细胞.结论 PEDF的表达降低在恶性黑素瘤的发病机制中可能起一定作用.     

核因子κB和c-myc在尖锐湿疣皮损角质形成细胞中的表达

目的 探讨核因子-κB(NF-κB)和c-myc在尖锐湿疣皮损角质形成细胞中的表达。方法 采用原位杂交方法检测尖锐湿疣50例,确定为HPV6/11阳性;采用免疫组化En Vision二步法检测50例尖锐湿疣患者皮损和25例正常人皮肤(包皮)中NF-κB和c-myc的表达及分布。结果 ①与正常人皮肤对照组相比,尖锐湿疣皮损角质形成细胞中NF-κB和c-myc的表达均有不同程度增强(前者U=6.286,P<0.01;后者U=4.356,P<0.01)。NF-κB表达主要分布于棘细胞层,阳性信号定位于胞浆。c-myc表达主要分布于表皮全层或棘细胞层和基底层,阳性信号定位于胞核。②尖锐湿疣皮损中,NF-κB与c-myc的表达呈正相关(r=0.89,P<0.01)。结论 在HPV6/11感染时,角质形成细胞中转录因子NF-κB和c-myc的表达增高,可能均参与HPV感染细胞增殖的调控。     

自体外周血纯化造血干细胞移植治疗系统性红斑狼疮

目的 探讨自体外周血纯化造血干细胞移植治疗系统性红斑狼疮(SLE)的疗效和安全性。方法 对9例SLE患者进行自体外周血纯化造血干细胞移植。采集的干细胞的计数为(2.37～9.9)×10⁸/kg。预处理方案是环磷酰胺50 mg·kg^-1·d^-1静脉滴注,连用4 d(造血干细胞回输前2～5d)。抗胸腺球蛋白抗体2.5 mg·kg^-1·d^-1静脉滴注,连用4d。同时碱化和水化尿液,保护心、肝和肾功能。从移植后临床表现、SLE相关的免疫学指标的变化,移植后造血重建情况,移植的并发症等方面进行评价。结果 9例患者均获得成功植入,外周血白细胞总数>1.0×10>/L的时间为移植后7～15 d,血小板>20×10⁹/L时间为移植后0～21d。所有患者均于移植后面部红斑等临床症状完全消失,大部分患者自身抗体转阴。9例患者均出现轻重不一的血清病样反应,1例出现严重的肾衰和心衰,3例有出血性膀胱炎,1例出现心因性精神障碍,1例发生会阴部念珠菌感染。结论 随访1年结果表明,自体外周血纯化造血干细胞移植治疗SLE的近期疗效显著,且相对安全。     

18味中药乙醇提取物对小鼠B16黑素瘤细胞增殖及黑素生成的影响

目的研究中药乙醇提取物对小鼠B16黑素瘤细胞增殖及黑素合成的影响。方法以MTT法测定培养的B16黑素瘤细胞的增殖活性:NaOH法测定黑素生成量;体外氧化多巴反应方法测定酪氨酸酶活性。结果与空白对照组相比,18种中药乙醇提取物中,有9种提取物对1种以上指标有显著性作用(P<0.05或P<0.01)。沙苑子、甘草、山慈姑、薄荷、苦参、夏枯草、黄芩、黑芝麻、墨旱莲可明显促进B16黑素瘤细胞增殖,甘草、山慈姑、薄荷、苦参、夏枯草、何首乌、黑芝麻、墨旱莲明显增加黑素含量,山慈姑、薄荷、苦参、夏枯草、黑芝麻、墨旱莲明显增加酪氨酸酶活性,山慈姑、薄荷、苦参、夏枯草、黑芝麻和墨旱莲的提取物对3种指标均有显著性作用(P<0.05或P<0.01)。结论山慈姑等6种中药的乙醇提取物具有促进黑素细胞增殖和合成黑素的作用。     

Kidney regeneration: Where we are and future perspectives

In 2012, about 16487 people received kidney transplants in the United States, whereas 95022 candidates were on the waiting list by the end of the year. Despite advances in renal transplant immunology, approximately 40% of recipients will die or lose graft within 10 years. The limitations of current therapies for renal failure have led researchers to explore the development of modalities that could improve, restore, or replace the renal function. The aim of this paper is to describe a reasonable approach for kidney regeneration and review the current literature regarding cell sources and mechanisms to develop a bioengineering kidney. Due to kidneys peculiar anatomy, extracellular matrix based scaffolds are rational starting point for their regeneration. The perfusion of detergents through the kidney vasculature is an efficient method for delivering decellularizing agents to cells and for removing of cellular material from the tissue. Many efforts have focused on the search of a reliable cell source to provide enrichment for achieving stable renal cell systems. For an efficient bioengineered kidney, these cells must be attached to the organ and then maturated into the bioractors, which simulates the human body environment. A functional bioengineered kidney is still a big challenge for scientists. In the last ten years we have got many improvements on the field of solid organ regeneration; however, we are still far away from the main target. Currently, regenerative centers worldwide have been striving to find feasible strategies to develop bioengineered kidneys. Cell-scaffold technology gives hope to end-stage renal disease patients who struggle with morbidity and mortality due to extended periods on dialysis or immunosupression. The potential of bioengineered organ is to provide a reliable source of organs, which can be refunctionalized and transplanted.     

Role of IL-10 in the progression of kidney disease

Interleukin-10 (IL-10), a cytokine with anti-inflammatory and immunomodulatory functions, regulates the biology of B and T cells. The present review describes the role of IL-10 in normal renal physiology, during acute kidney injury and in the development of chronic renal failure. We further discuss IL-10-induced cellular and molecular pathways and their link to the progression of kidney injury.     

Use of intralesional collagenase in the treatment of peyronie&rsquo;s disease: A review

AIM: To review the relevant literature in an effort to examine the body of evidence available to date. METHODS: Ovid MEDLINE search database was queried using MeSH terms “penile induration”, “peyronie’s disease”, “Collagenases” and “Collagenase” using various permutations. No temporal parameters were employed. RESULTS: In all, 5 relevant clinical trials were isolated from 34 results. These trials were analyzed using the Oxford Centre for Evidence-Based Medicine criteria. They were further examined based on study design and methods; the primary and secondary outcomes were reviewed for treatment efficacy and collagenase-related side effects. CONCLUSION: Intralesional collagenase appears to be safe and effective in the non-surgical treatment of Peyronie’s disease. However, the data remains limited and further inquiries into the safety of collagenase, treatment standardization and standardized outcomes reporting remain necessary. Furthermore, studies comparing intralesional collagenase to alternative medical and surgical therapy will be important in guiding the future treatment decision process.     

Stop chronic kidney disease progression: Time is approaching

Progression of chronic kidney disease (CKD) is inevitable. However, the last decade has witnessed tremendous achievements in this field. Today we are optimistic; the dream of withholding this progression is about to be realistic. The recent discoveries in the field of CKD management involved most of the individual diseases leading the patients to end-stage renal disease. Most of these advances involved patients suffering diabetic kidney disease, chronic glomerulonephritis, polycystic kidney disease, renal amyloidosis and chronic tubulointerstitial disease. The chronic systemic inflammatory status and increased oxidative stress were also investigated. This inflammatory status influences the anti-senescence Klotho gene expression. The role of Klotho in CKD progression together with its therapeutic value are explored. The role of gut as a major source of inflammation, the pathogenesis of intestinal mucosal barrier damage, the role of intestinal alkaline phosphatase and the dietary and therapeutic implications add a novel therapeutic tool to delay CKD progression.