Membranous nephropathy associated with thyroid-peroxidase antigen

A 6-year-old previously healthy Japanese girl was found to have dipstick 2+ proteinuria and a goiter based on the results of a routine school medical examination. Her serum free-thyroxine level was 4.98 ng/dL (normal range 0.95–1.74 ng/dL), thyroid-stimulating hormone (TSH) was less than 0.003 μU/mL (0.34–3.88 μU/mL), anti-microsomal (anti-thyroid-peroxidase) antibody was 1600 T (up to 100), anti-thyroglobulin antibody was 400 T (up to 100), and TSH-receptor antibody was 84% (up to ±10%). These results are consistent with a diagnosis of Graves’ disease. Electron microscopy examination of a renal biopsy specimen revealed electron-dense deposits located in the subepithelial spaces, and immunofluorescence microscopy examination demonstrated bright granular stainings of immunoglobulin G along the glomerular capillary walls. These findings are characteristic of membranous nephropathy. To investigate the relationship between the membranous nephropathy and Graves’ disease, we carried out a second immunofluorescence study, which revealed that the immunoglobulin G granular deposits corresponded to glomerular granular staining of thyroid-peroxidase, whereas staining for thyroglobulin was absent. It was therefore assumed that the deposition of immune complexes mediated by thyroid-peroxidase had caused the membranous nephropathy in this patient. This is the first report of membranous nephropathy associated with Graves’ disease in which deposits of thyroid-peroxidase, rather than thyroglobulin, have been confirmed in the kidney. This study was presented in the 14th congress of International Pediatric Nephrology Association (IPNA), Budapest, Hungary, 2007.     

前列腺素E1治疗糖尿病肾病Ⅲ期临床疗效观察

目的观察前列腺素E1（PGEl）治疗糖尿病肾病Ⅲ期（DN—111）的临床疗效。方法35例糖尿病。肾病（DN）患者予PGEl治疗2周,并观察24h尿蛋白、24h尿微量白蛋白、空腹血糖、餐后2h血糖、血肌酐、血压的变化及不良反应等。结果PC-E1治疗2周后,24h尿蛋白、24h尿微量白蛋白较前均明显下降（P〈0．01）,其余检测指标虽较前降低,但差异无统计学意义（P〉0．05）。患者治疗后无肝功能异常改变,治疗期间无皮疹、血管炎等不良反应发生。结论PGEl可减轻DN．111患者尿蛋白的排泄,延缓DN的发展和恶化。     

血小板反应蛋白-1在糖尿病大鼠模型肾损害中的作用及机制初步探讨

目的：观察血小板反应蛋白-1（thrombospondin-1,TSP-1）在链脲佐菌素诱导的糖尿病（diabetes mellitus, DM）大鼠模型肾脏中的表达,初步探讨TSP-1在糖尿病肾病大鼠发病机制中的作用及与糖尿病肾损害的关系。方法：成年雄性SD大鼠80只,随机分为正常对照组（ n＝15）和实验组（ n＝65）。采用STZ 70 mg/kg单次腹腔注射建立DM大鼠模型,按照成模标准去除未成模大鼠。检测各组大鼠空腹血糖（ fasting blood glucose,FBG）、尿蛋白及肾功能;分别于2,4,8周处死各组大鼠,通过HE染色观察各组大鼠肾脏的病理改变,免疫荧光观察TSP-1在各组大鼠肾脏的分布;PCR检测肾组织TSP-1和转录生长因子β1（ transforming growth factor,TGF-β1）基因表达水平;采用酶联免疫吸附法（ ELISA）检测肾组织活性TGF-β1水平;Western杂交检测TSP-1的动态变化。分别对尿蛋白、肾功能、肾脏病理损害、活性TGF-β1与TSP-1蛋白表达的相关性进行分析。结果：HE染色可见DM组大鼠肾小球系膜基质增生,肾小球可见分叶现象、K-W结节等典型的糖尿病肾病损伤特点。与正常对照组相比,DM组大鼠的FBG、尿蛋白、肌酐、尿素氮水平均显著增加（ P﹤0．05）,TSP-1在DM组大鼠主要分布于肾小管、肾小球系膜细胞,其蛋白表达在2周时即明显增加,一直持续到第8周。DM 组大鼠肾脏TSP-1的积分光密度（ integrated optical density,IOD）与尿蛋白、肾脏病理损害、肌酐、尿素氮水平、活性TGF-β1浓度均呈正相关。结论：持续高血糖状态可以诱导大鼠肾脏病理损害,引起尿蛋白升高、肾功能异常;高血糖可诱导大鼠肾脏TSP-1蛋白高表达。TSP-1蛋白的高表达可能通过激活TGF-β1信号通路参与DM大鼠蛋白尿的产生及肾损害的发生发展。     

具有显著蛋白尿的IgA肾病临床与病理分析

目的分析显著蛋白尿IgA肾病患者的临床与病理特征及肾小管间质损害的影响因素。方法以尿蛋白2．0g／24h为界，将IgA肾病患者分为：显著蛋白尿组（A）及非显著蛋白尿组（B），比较其临床及病理的差异，并分析肾小管间质损害的影响因素。结果A组血清白蛋白低于B组（P〈0.01）；其脂蛋白（a）、肾小球及小管间质病理积分均高于B组（P〈0．01或P〈0．05）。逐步回归法显示，仅尿蛋白定量对肾小管间质损害的影响差异有统计学意义（β=0．31，t=3．20，P〈0．01）。结论显著蛋白尿IgA肾病患者的肾小球及小管间质损害更为严重；蛋白尿可能是肾小管间质损害的独立致病因子。     

Intermittent microalbuminuria in children with type 1 diabetes mellitus without clinical evidence of nephropathy

Microalbuminura (MA) was determined in 127 children and adolescents (age 3–21 years) with type 1 (insulin-dependent) diabetes mellitus. Patients with clinical evidence of long-term complications or macroproteinuria were excluded. Urinary albumin excretion was measured in a nocturnal 12-h collection and correlated with the albumin/creatinine ratio of a urine sample freshly voided on the morning immediately following the collection. The patients were divided into group A (n=83, age <16 years, duration of diabetes 1–13 years, mean 4.4) and group B (n=44, age >16 years, duration of diabetes 1–19 years, mean 8.7) and compared with appropriate controls. MA above 15 g/min was present in 11 of 83 (13.3%) patients in group A and in 7 of 44 (15.9%) in group B. In a repeat urine collection at least 3 months later elevated MA persisted in 1 of 11 (group A) and in 4 of 7 (group B) patients. There was no correlation between increased MA in a 12-h urine collection and the albumin/creatinine ratio in a subsequently voided urine sample. MA was not strictly dependent on age, sex, duration of diabetes, haemoglobin A₁, mean arterial blood pressure, plasma creatinine, creatinine clearance or serum beta-2-microglobulin. Further systematic studies and careful follow up are necessary to appraise whether intermittent MA is indeed an early manifestation of incipient kidney disease in children with type 1 diabetes.Abbreviations MA microalbuminuria - Hb haemoglobin     

Glomerulonephritis in Behçet’s Disease: Report of Seven Cases and Review of the Literature

Despite being recognised much more frequently than in the past, renal involvement has not previously been regarded as a feature of Behcet's disease (BD). In this study we aimed to assess the frequency of renal involvement in BD by performing urinalyses of 674 consecutive BD patients; we also retrospectively evaluated the charts of 4212 BD patients for the incidence of glomerulonephritis (GN). Urinary abnormalities (proteinuria and/or haematuria) were present in 10.8%; and during a period of 23 years GN was detected by renal biopsy in seven (0.16%) BD patients. Two patients with GN were lost to follow-up; end-stage renal failure developed in only one patient, and she underwent renal transplantation. We were unable to determine any pathognomonic feature that was predictive of renal involvement. Although males tend to have a more serious clinical course of BD the incidences of urinary abnormalities and GN were similar in both sexes in our series. According to our results, we can conclude that urinary abnormalities are more frequent in BD; however, serious renal lesions develop in only very few of these patients.     

Comparative effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on blood pressure and the kidney

Many clinicians are uncomfortable about using angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers (AT(1)-blockers) to treat patients with renal disease because of concerns about increasing serum creatinine levels. However, the benefits of these medications, particularly their efficacy in slowing the progression of renal disease, outweigh such concerns. ACE inhibitors are effective in patients with type 1 diabetes and renal disease, as well as in those with nondiabetic renal disease and proteinuria >0.5 g/d. AT(1)-blockers slow the progression of diabetic nephropathy in patients with type 2 diabetes. Although these classes of medications should not be used in patients with severe renal insufficiency (e.g., glomerular filtration rate <20 mL/min), they may be beneficial in patients with mild-to-moderate renal insufficiency. Nonetheless, caution should be exercised in those with a glomerular filtration rate <30 mL/min, and serum creatinine and potassium levels should be checked approximately 1 week after starting treatment. There is also evidence suggesting that these medications lead to greater reductions in blood pressure and proteinuria when used in combination than when alone. The purpose of this paper is to review the mechanisms of action of these two classes of medication, as well as the experimental and clinical evidence that they slow the progression of renal disease.     

肾性蛋白尿非特异性治疗进展

肾脏疾病蛋白尿的水平与慢性肾衰竭进展的速度密切相关。至今研究表明,血管紧张素转换酶抑制剂(ACEI)可降低蛋白尿,延缓肾功能恶化的进展,推荐治疗剂量为血压耐受量,对尿蛋白<1g较>1g者疗效更佳。血管紧张素Ⅱ受体拮抗剂(ARB),也具有降低蛋白尿的作用,大剂量优于常规剂量。ACEI和ARB联合应用比单个药物大剂量应用有更强的降尿蛋白作用。非二氢吡啶类钙通道阻滞剂也可减少糖尿病肾病蛋白尿,是否确有与降压作用无关的肾脏保护作用,尚未取得一致意见。前列腺素E1及抗醛固酮治疗都有一定的疗效。他汀类药物降低蛋白尿的程度究竟如何还需进一步观察。羟苯磺酸钙可降低糖尿病肾病尿白蛋白的排泄,降低非糖尿病肾病蛋白尿尚处于观察阶段。     

2型糖尿病发生蛋白尿的危险因素配对病例对照研究

目的　探讨 2型糖尿病 (DM)患者发生蛋白尿的危险因素。方法　回顾性分析了按年龄、性别、种族、居住地匹配的两组 2型DM患者 ,其中一组为非蛋白尿组 (尿蛋白 <30 0mg/2 4h ,n =10 6 ) ,另一组为蛋白尿组 (尿蛋白≥ 5 0 0mg/2 4h ,n =10 6 )。资料处理使用条件logistic回归分析。结果　职业、DM病程、血糖控制情况、高血压史、高血压病程、患DM后蔬菜摄入量均分别与蛋白尿的发生有统计学关联。相应的比值比及 95 %的可信区间分别为 2 .4 2 9(1.2 99～ 4 .5 4 2 )、1.0 78(1.0 2 9～ 1.131)、2 .316 (1.341～ 3.998)、1.810 (1.0 5 9～ 3.0 92 )、1.0 4 3(1.0 12～ 1.0 74 )和 0 .5 5 1(0 .334～ 0 .90 7)。但未发现DM家族史、高血压家族史、吸烟、其他饮食习惯与 2型DM发生蛋白尿有统计学联系。拟合多变量logistic回归模型 ,应变量为发生蛋白尿 ,自变量包括DM病程、血糖控制情况和高血压史。结论　对于 2型DM患者 ,体力劳动者发生蛋白尿的危险性较脑力劳动者大 ;糖尿病病程长 ,血糖控制差 ,有高血压史均可独立增加其发生蛋白尿的危险性 ;而患DM后 ,日蔬菜摄入量多则可减少发生蛋白尿的危险性     

肾炎宁胶囊治疗气虚湿瘀型慢性肾炎蛋白尿的疗效观察

目的观察应用肾炎宁胶囊治疗气虚湿瘀型慢性肾炎患者蛋白尿及证候的改善。方法将62例患者随机分为2组，治疗组32例服用肾炎宁胶囊，对照组30例口服肾炎康复片治疗，均以3mo为1疗程，记录主要症状及观测治疗前后尿蛋白水平。结果2组对尿蛋白的排泄量的治疗效果一致；但在主要证候如乏力、腰酸、水肿等症状的改善程度方面治疗组优于对照组。结论肾炎宁胶囊对气虚湿瘀型慢性肾炎有较好疗效，可明显降低尿蛋白的排泄量改善临床主要症状。