Purpose IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis and a leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Recently, some case reports have shown that COL4A5 mutation is associated with IgAN. Here, we identified a new COL4A5 gene mutation in IgAN in a Chinese family. Materials and Methods In the present study, the proband and his 23-year-old younger brother were both diagnosed with IgAN, manifested as haematuria, proteinuria and chronic kidney injury without hearing loss or ocular symptoms. Additionally, the proband's 30-year-old younger brother, also diagnosed with ESKD, had been undergoing dialysis for 2 years with normal hearing and eyesight. To exclude genetic disease, we conducted whole-exome sequencing and Sanger sequencing assays. Results We found a new mutation in the COL4A5 gene (chrX:107 814 698, c.438+2->AAACCAATTATA-), a novel insertion mutation. Using vector transcription and Minigene transcriptional analyses, we verified, for the first time, the novel mutation pathogenicity of the COL4A5 gene. Conclusion Together with other published data, we suggest that genetic screening should be performed in IgAN, particularly for patients with a familial history. The effects of different mutated splice sites of the COL4A5 gene, as well as the tissue specificity of the splicing machinery contributing to the pathogenesis and prognosis of IgAN, remains unclear and warrants further exploration in the future.

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease, with frequent flares amid remissions. Basophils contribute to the immunopathogenesis of SLE. This retrospective clinical study evaluated blood basophil count as a potential marker of SLE activity. This study included 213 patients with SLE, 70 with non-SLE chronic kidney disease (CKD), and 100 healthy volunteers. SLE disease activity was scored using the SLE Disease Activity Index (SLEDAI). Baseline and post-immunosuppressant bioparameters were compared in patients with active SLE, with second samples taken at total SLEDAI ≤4. Blood basophil counts and other conventional biomarkers were compared among the groups. Among the 213 SLE patients (192 women, 21 men; mean age 33.0 ± 12.0 years), 149 had active disease. Basophil counts were significantly lower in patients with SLE than in patients with non-SLE CKD and healthy controls (0.009 ± 0.010 vs. 0.025 ± 0.015 vs. 0.022 ± 0.010 × 109/L, p <0.001), and lower in patients with active than inactive SLE (0.008 ± 0.009 vs. 0.014 ± 0.012 × 109/L, p <0.001). Basophil counts in SLE patients were significantly higher after than before immunosuppressive treatment (0.021 ± 0.017 vs. 0.008 ± 0.008 × 109/L, p <0.001) and correlated with total SLEDAI score (r = −0.30, p <0.001). Receiver operator curve analysis showed that basophil counts were similar to conventional markers (leukocytes, platelets, and double-stranded (ds) DNA IgG) in differentiating active from inactive SLE. These findings indicate that blood basophil counts may be a useful biomarker in evaluating SLE activity.

目的探讨Wnt/β-catenin信号通路在高糖诱导的足细胞转分化中的作用机制。方法收集原代培养的大鼠足细胞,设置正常糖组（D-葡萄糖5 mmol/L）、高糖组（D-葡萄糖15 mmol/L、30 mmol/L）、高渗对照组（甘露醇25 mmol/L+D-葡萄糖5 mmol/L）。观察细胞形态并采用间接免疫荧光法检测nephrin和Wt-1的表达;免疫印迹半定量检测nephrin、α-SMA、活化β-catenin及Wnt-1的表达。结果 nephrin以颗粒状及线状表达于足细胞胞膜、胞质及胞核周围,Wt-1表达于胞核。48 h后,正常糖组nephrin相对表达量为（0.967±0.065）,15 mmol/L高糖组为（0.771±0.068）,30 mmol/L高糖组为（0.112±0.042）,高渗对照组为（1.096±0.104）,差异有统计学意义（F=106.848,P=0.000）;正常糖组α-SMA相对表达量为（0.360±0.023）,15 mmol/L高糖组为（0.430±0.008）,30 mmol/L高糖组为（0.524±0.040）,高渗对照组为（0.320±0.030）,差异有统计学意义（F=18.149,P=0.001）。高糖作用12 h后,足细胞Wnt-1及活化β-catenin表达开始升高,24 h时达到高峰。DKK1有助于增加高糖诱导的nephrin的表达,降低α-SMA的表达。结论高糖可诱导足细胞发生表型转化,而Wnt/β-catenin信号通路可能参与了高糖诱导的足细胞表型转化。

Objective To explore the influence of fenofibrate on glomerular podocytes cultured under high glucose to study the mechanism of chronic kidney disease in diabetes in the early stage. Methods The rat glomeruli were isolated and gathered for primary culture.The cells were randomized into normal glucose(NG)group,high glucose(HG)group,fenofibrate 50μmol/L(F50)group,fenofibrate 100(F100)group,and fenofibrate 200(F200)group.The culture was continued for 48h.The morphological changes of podocytes were observed.The expression of nephrin was determined with Western blot method. Results Compared with the NG group,the podocytic-process retraction and partial effacement and intercellular junction losing appeared in the HG group,the expression of nephrin was lowered(P0.05).Compared with the HG group,there was a recovery of podocytic-process and upregulation of expression of nephrin in the F50and F100groups(P0.05).In the F200group,there was a severe damage of the podocytes,including the podocytic-process decrease,even disappearance,and inhibited expression of nephrin,with a statistically significant difference from that of the F50and F100groups(P0.05). Conclusion Damage of podocytes caused by high-glucose may be the mechanism of chronic kidney disease in diabetes in the early stage.Fenofibrate protects podocytes by activating PPAR-α.

糖尿病肾病是世界范围内导致终末期肾疾病的最常见的继发性肾脏疾病.肾小球基底膜增厚、系膜基质堆积、肾脏纤维化及蛋白尿是糖尿病肾病最主要的病理和临床特点.然而糖尿病肾病发病机制尚不清楚.研究表明经典wnt信号通路广泛参与慢性肾脏疾病的发生发展,如蛋白尿性肾病、肾脏纤维化等,包括糖尿病肾病.了解该信号通路与糖尿病肾病之间的关系对进一步了解糖尿病肾病的发病机制及治疗有重要作用.本文就经典wnt信号通路与糖尿病肾病病理和临床特点之间的关系展开论述.

了解致病菌谱是合理选择抗生素的基础 尿路感染是指各种病原微生物在泌尿系统中生长、繁殖引起的尿路感染性疾病.发病率女性明显高于男性,比例约8∶1,多见于育龄期妇女、老年人;男性极少发生尿路感染,但＞50岁男性常因前列腺肥大,尿路感染发生率相应增高.

Insulin resistance and hyperinsulinmia could happen at early stage of chronic kidney disease. Inflammation, oxidative stress, angiotesin II, obesity, deficiency of 1, 25-dihydroxyvitamin D, hyperparathyroidism and anemia can influenc the secretion of insulin and induce insulin resistance. Insulin resistance induces kidney damage directly and indirectly by different mechanisms. Insulin resistance and chronic kidney disease interact as both cause and effect.

Objective To verify the adaptability of CKD-EPI equation developed based on cystatin C in America in 2008 among Chinese patients with chronic kidney disease (CKD).Methods Between December 2008 and April 2009, 68 non - dialysis CKD patients were recruited and calculated for their glomerular filtration rates(GFRs) by Cockcroft-Gault equation, simplified MDRD equation, modified MDRD equation and gates method with 99mTc-DTPA (cGFR, aGFR, mGFR, gGFR) and three CKD-EPI estimating equations developed based on cystatin C (CyslGFR, Cys2GFR, Cys3GFR).All the results above were then compared and analyzed with tGFR determined by double plasma sample method of GFR with 99mTc-DTPA.Results Pearson analysis demonstrated that seven estimated GFRs (cGFR, aGFR, mGFR, gGFR,cyslGFR, cys2GFR, cys3GFR) were significantly correlated with tGFR, with Cys3GFR showing the highest correlation coefficient (0.93) , followed by gGFR (0.91) , mGFR (0.89) , Cys2GFR (0.88) , CyslGFR (0.85), cGFR(0.85), and aGFR(0.83).Cys3GFR yielded results that were more accurate than did aGFR or CyslGFR.Bland-Altman analysis demonstrated that Cys3GFR had the best consistency with tGFR which did not exceed the predetermined limits.The outcome of linear regression showed that the modified MDRD equation had the least deviation and the highest precision.Conclusion In Chinese population, the third CKD-EPI equation (Cys3GFR) including cystatin, creatinine and demographic statistics has favorably greater accuracy, and best consistency and correlation with tGFR, as compared with the first CKD-EPI equation based on cystatin C alone, Cockcroft-Gault equation or simplified MDRD equation.

目的 分析糖代谢异常的代谢综合征患者及在不同肾损害情况下4型心肾综合征的患病率.方法 选取2009年1月~2009年7月在中山大学孙逸仙纪念医院内科住院的合并T2DM或IFG、IGT的代谢综合征患者.统计肾损害的患病率及临床特征,依有无肾损害、肾损害的形式分析4型心肾综合征的患病率.结果 531例患者中52.73%发生肾损害,肾损害组冠心病、心功能不全患病率均较非肾损害组高(P<0.05),蛋白尿组冠心病、心功能不全的患病率均显著高于非肾损害组(P<0.05),肾功能下降组较非肾损害组冠心病患病率高(P<0.01),心功能不全的患病率也较高(P<0.05).结论 糖代谢异常的代谢综合征患者肾损害的发生率高,糖代谢异常的代谢综合征患者合并肾损害后心血管事件患病率进一步增高.

目的建立一种重复性好、操作简便的大鼠足细胞培养方法。方法取体质量200～220g的健康雌性SD大鼠,无菌取肾后通过差异过筛法分别通过80、150、200目细胞筛网,收集200目筛网上肾小球进行接种,利用植块法将接种培养面向上放置,4.5h后将培养瓶翻转过来正常放置于37℃、5%CO2的恒温恒湿培养箱进行孵育。采用形态学观察和细胞间接免疫荧光技术,对足细胞进行鉴定,并用流式细胞仪进行足细胞纯度分析。结果 5d后可见绝大部分肾小球贴壁并有少许肾小球周围有细胞爬出,7～8d可见所有肾小球周围有大量细胞爬出,胰酶消化后传代培养。形态学及特异性抗体WT-1、nephrin鉴定为足细胞。流式细胞仪分析细胞纯度99%左右。结论差异过筛法分离大鼠肾小球,结合植块法促进肾小球贴壁,可简单、高效地培养出原代足细胞,且具备足细胞生物学特性,且在操作简单的情况下细胞产量、纯度与国外文献报道的相当。

Objectives To explore the effect of the modified simultaneous pancreatic-kidney transplantation(SPK)as the preferred treatment for patients with type 2 diabetic mellitus(T2DM)associated with uremia.Methods Modified SPK with the enteric drainage(ED)of exocrine pancreatic secretions was performed on one patient suffering from T2DM and uremia.And the allograft exocrine secretions was drained into the proximal jejunum via a side-to-side duodenojejunostomy(no Roux-en-Y).Results Successful recovery of the kidney and pancreas grafts were observed.The laboratory examination showed continuous decreased serum creatinine(Scr)and the level of Scr was almost back to normal on day 3 post-transplantation.The serum and urinary amylase of this patient were returned to normal.And the fasting blood glucose levels were also returned to normal in 10 days after transplantation.The patient was discharged from hospital 14 days after transplantation and had been followed up for 27 months.The kidney graft and pancreatic allograft of function of the patient were all normal during follow-up.The patient had no complication such as graft thrombosis,pancreatic fistula,pancreatitis and rejection.The function of pancreas and kidney grafts remained normal up till now.Conclusion The modified ED-SPK without Roux-en-Y is a simple,safe and effective treatment for T2DM with uremia.

目的 探讨基质金属蛋白酶2(MMP-2)和单核细胞趋化因子-1(MCP-1)在IgA肾病肾组织的表达强度及其在该病早期肾损害发病机制中的作用.方法 将30例IgA肾病患者经肾脏活体组织检查的肾组织和10例切除肾肿瘤患者正常肾组织,进行MMP-2、MCP-1、Ⅳ型胶原免疫组织化学检测并进行半定量分析,按其组织学改变Lee分级标准和肾小管间质病变程度进行分组和分级,同时检测肾功能、24 h尿蛋白定量等临床指标,并与组织学、免疫组织化学检测结果进行相关分析.结果 在IgA肾病轻度肾损害阶段,MMP-2和MCP-1表达水平显著高于正常对照(P<0.05),随着病变级别加重,MMP-2和MCP-1在肾小管问质的表达呈逐渐减少趋势(P<0.05),而Ⅳ型胶原在肾小管间质表达随肾损害加重呈逐渐增加趋势(P<0.01).Spearman相关分析显示,MMP-2和MCP-1表达水平与肾小管间质炎症细胞浸润程度呈正相关(P<0.05),与Ⅳ型胶原表达水平旱负相关(P<0.05).结论 MMP-2和MCP-1可能参与IgA肾病早期单个核细胞浸润等早期肾损害发病机制.

Background: Perceptions of exercise benefits and barriers affect exercise behavior. Because of the clinical course and treatment, dialysis patients differ from the general population in their perceptions of exercise benefits and barriers, especially the latter. At present, no valid instruments for assessing perceived exercise benefits and barriers in dialysis patients are available.Objectives: Our goal was to develop and test the psychometric properties of the Dialysis patient-perceived Exercise Benefits and Barriers Scale (DPEBBS).Methods: A literature review and two focus groups were conducted to generate the initial item pool. An expert panel examined the content validity. Then, 269 Chinese hemodialysis patients were recruited by convenience sampling. Exploratory and confirmatory factor analyses were used to test construct validity. Finally, internal consistency and test-retest reliability were assessed.Results: The expert panel determined that the content validity index was satisfactory. The final 24-item scale consisted of six factors explaining 57% of the total variance in the data. Confirmative factor analysis supported the six-factor structure and a higher-order model. Cronbach's alpha was 0.87 for the total scale, and 0.84 for test-retest reliability.Conclusion: The DPEBBS was a valid and reliable instrument for evaluating dialysis patients' perceived benefits and barriers to exercise. The application value of this scale remains to be investigated by increasing the sample size and evaluating patients undergoing different dialysis modalities and coming from different regions and cultural backgrounds. (C) 2009 Elsevier Ltd. All rights reserved.

Metabolic syndrome has become an important public health problem today.Insulin resistance which is the pathologic determiner of metabolic syndrome induces kidney damage by different mechanisms.The kidney disease affects glucose metabolism and insulin resistance progression as well.It is important to determine the relationship between them for prevention and treatment of kidney disease.

目的 研究白细胞介素10(IL-10)基因启动子区-3575和-2763位点多态性在中国南方地区汉族人群中的分布及其与系统性红斑狼疮(SLE)和狼疮肾炎(LN)的关系.方法 符合1982年美国风湿病学会SLE诊断标准的SLE患者103例,包括男13例,女90例,其中62例为LN.健康对照组110例,其中男21例,女89例.全部对象均为无血缘关系的中国南方地区汉族人群.应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,对上述对象进行IL-10基因启动子区-3575和-2763位点多态性检测.结果 IL-10基因启动子区-3575位点多态性在中国南方地区汉族人群中普遍存在.与健康对照组比较,SLE患者IL-10基因启动子区-3575位点TT基因型频率和T等位基因频率均明显降低(P＜0.05).与同性别健康对照者比较,女性SLE患者IL-10基因启动子区-3575位点TF基因型频率、T等位基因频率和携带者频率分布均明显降低(P＜0.05).LN患者和健康对照组IL-10基因启动子区-3575位点各基因型频率、等位基因频率和携带者频率分布等差异均无统计学意义.在SLE患者和健康对照者均未发现IL-10基因启动子区-2763位点多态现象,均为AA基因型.结论 IL-10基因启动子区-3575位点多态性与SLE有关,而与LN无关.IL-10基因可能是中国南方汉族人SLE的易感基因.

BACKGROUND Osteopontin (OPN) is one kind of cytokine which can play a number of roles in promoting activation of T lymphocyte, regulating balance between Th1 and Th2, participating in cell-induced immunologic response and stimulating B lymphocyte to express multi-clone antibodies. Some researches have showed that OPN may be involved in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study was to investigate possible association of a single nucleotide polymorphism (SNP) at position 9250 in exon 7 of the OPN gene (OPN gene 9250) with SLE in Chinese patients. METHODS Totally 158 patients (18 males and 140 females) fulfilled the revised criteria for SLE by the American College of Rheumatology in 1982 and 180 healthy volunteer controls (34 males and 146 females), all from the south of China, consented to participate in the study. OPN gene 9250 polymorphism was detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). RESULTS The frequency of TT genotype of the OPN gene 9250 was significantly lower (52.5% vs 70%, P < 0.05) and the frequency of TC genotype of the OPN gene 9250 was significantly higher (43.7% vs 29.4%, P < 0.05) in SLE patients than in controls. There were significant differences in OPN gene 9250 allele and phenotype frequencies between the SLE patients and controls (P < 0.05). When the SLE patients and controls were separated into men and women, significant differences of frequencies were noted in TT genotype, TC genotype and allele of the OPN gene 9250 in women (P < 0.05) but not in men (P > 0.05). CONCLUSIONS OPN gene 9250 polymorphism appears to be associated with susceptibility to SLE in Chinese Han ethnic population.

AIM:To observe the therapeutic effects of saikosaponin-d(SSd) extracted from Bupleurum falcatum L.on lupus nephritis in NZBWF1 mice. METHODS: Twenty female NZBWF1 mice were randomized into three groups: SSd treatment group Ⅰ [n=8, intraperitoneal injection (ip) SSd, 2 mg/(kg·d)]; SSd treatment groupⅡ [n=6, ip SSd, 4 mg/(kg·d)]; Blank control group (group Ⅲ, n=6). The experiment lasted for 6 weeks. Urine protein content, concentration of creatinine, corticosterone and anti-ds-DNA antibodies in serum were detected. Kidney histological analysis was carried out by using light microscope, immunofluorescence, and electron microscope. Expression of IL-6 and IL-10 mRNA in renal tissue was detected by using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Compared with blank control group, in the SSd treatment groups, urine protein content, concentration of creatinine and anti-ds-DNA antibodies in serum, and expression of IL-6 and IL-10 mRNA in renal tissue were decreased, and corticosterone concentration in serum was increased significantly (P0.05); glomerular endothelial and mesangial hypercellularity, hyalinosis, exudation and sclerosis were modified; percentage of damaged tubules was decreased; immune complex deposits of IgG, IgA, and IgM in glomeruli were reduced. CONCLUSION: SSd has therapeutical effects on lupus nephritis in NZBWF1 mice.

Objective To observe the effects of saikosaponin-d(SSd)extracted from Bupleurum falcatum L.on urine protein content and improving the damage of renal tissue in NZBWF1 mice.Methods Twenty famale NZBWF1 mice,eighteen weeks old,were randomized into three groups:(1)group Ⅰ(SSd treatment 1st group,intraperitoneal injection(ip)SSd 0.2 mg·100 g-1·d-1);(2)group Ⅱ(SSd treatment 2nd group,ip SSd 0.4 mg·100 g-1·d-1);(3)group Ⅲ(Blank control group).The experiment lasted for 6 weeks.Urine protein content in NZBWF1 mice was detected using the method of Coomassie brilliant blue.Kidney histological analysis was carried out using light microscope,electron microscope,and immunofluorescence.Results At the end of the 2,4,6 weeks of experiment,compared with the control group,urine protein content was decreased significantly in the first and second group of SSd treatment(P0.05).Compared with the first group of SSd treatment,urine protein content was decreased remarkably in the second group of SSd treatment(P0.05).At the end of the 6 weeks of experiment,compared with the control group,in the group of SSd treatment,the proliferation of mesangial cells,hypercellularity,hyalinosis,glomerular sclerosis,and exudate was improved,the percentage of tubules that were damaged was decreased;the immune complex deposit of IgG,IgA,and IgM was reduced;the deposit and cellular proliferation was diminished,and coalesce phenomenon of foot process was improved which was observed in electron microscope.Conclusion Damage of glomerulus and nephric tubules can be improved,immune complex deposit in glomerulus and Urine protein content can be decreased by SSd treatment in NZBWF1 mice.