IgA肾病肾病综合征的临床和病理研究

目的：了解IgA肾病肾病综合征的临床和病理的特点及其与预后的关系。方法：观察72例经肾活检确诊为IgA肾病表现为肾病综合征的患的临床表现、实验室检查、病理改变、免疫组化、组织学定量分析及其与转归的关系。结果：患常见表现有高血压、肉眼和镜下血尿、贫血、氮质血症,病理改变多样;治疗后有22例完全缓解,15例部分缓解,16例呈持续性非肾病性蛋白尿,8例呈持续肾病性蛋白尿,10例发展为肾功能衰竭;其转归或激素敏感性与临床表现、蛋白尿选择性、小球病理形态、区膜区增宽和免疫沉着、小管间质病变及肾间质T淋巴和单核细胞分布显相关。结论：IgA肾病肾病综合征可有不同预后,其预后与临床表现、实验室发现、病理特点和免疫发病机理有关。     

IgA肾病肾病综合征临床病理特点及肾脏病理危险因素

目的：探讨IgA肾病肾病综合征患者临床病理特点及肾脏病理损害的危险因素。方法：选择1987年～2006年经肾活检确诊IgA肾病并表现为肾病综合征的患者118例，分析其临床病理特点，按肾脏病变轻重分为A组（n=34，包括Lee氏分级Ⅰ级、Ⅱ级）、B组（n=84，Ⅲ、Ⅳ、Ⅴ级），比较两组临床指标，并多因素分析影响肾脏病理损害的危险因素。结果：A、B两组高血压分别占11．8％ vs 63．1％；肾衰竭分别占15％ vs 41．7％；A、B两组尿蛋白≥6g／24h者分别占58．8％ vs 32．1％；尿红细胞满视野分别为14．7％ vs 50％。A组高血压、肾衰竭、镜下尿红细胞满视野发生率显著低于B组（P〈0．01），尿蛋白≥6g／24h发生率显著高于B组（P〈0．01）。A组平均动脉压、血肌酐明显低于B组（P〈0．01）；而尿蛋白定量、血红蛋白显著高于B组（P〈0．05）。多因素分析显示IgA肾病肾病综合征患者肾脏病理损害重的危险因素有平均动脉压、尿蛋白〈6g／24h、镜下尿RBC〉5．0×10^7／L（0R值分别为1．048，3．227，6．578；P值分别为0．034，0．047，0．002），血红蛋白是保护性因素（OR=0.723，P=0．035）。随着平均动脉压的升高、血红蛋白的降低、镜下尿红细胞数的增多，肾脏病理损害程度加重（P〈0．01）。结论：IgA肾病肾病综合征患者临床、病理表现存在差异，高血压、血红蛋白水平、24h尿蛋白排泄量、镜下尿红细胞程度有助于判断肾脏病理损害轻重。     

Interaction between GALNT12 and C1GALT1 Associates with Galactose-Deficient IgA1 and IgA Nephropathy

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来氟米特治疗表现为难治性肾病综合征的IgA肾病临床分析

目的：观察来氟米特治疗表现为难治性肾病综合征的IgA患者的疗效。方法：经常规治疗无效的此类IgA肾病患者38例,予以来氟米特治疗,观察治疗前、治疗后4周、8周、12周及6个月的24h尿蛋白定量、肝功能、肾功能、血脂、免疫球蛋白等相关临床指标以及用药期间所有不良反应。结果：治疗后尿蛋白定量明显减少,血清白蛋白升高,与治疗前相比,差异均有统计学意义（P〈0.05）。治疗6个月时完全缓解9例,占23.7%;显效11例,占28.95%;有效7例,占18.4%;总有效率71.1%;无效11例,占28.95%。不良反应轻微,患者耐受性良好。结论：来氟米特是治疗表现为难治性肾病综合征的IgA患者的一种安全有效药物。     

Entheses ultrasound assessment in primary Sjogren's syndrome

ObjectiveMusculoskeletal pain is a common complaint among patients with primary Sjogren's syndrome (pSS). Joints clinical examination is oftenly normal. A periarticular origin of this pain may be possible. Since clinical examination lacks sensitivity and precision, the use of musculoskeletal ultrasound (US) is more interesting in the evaluation of the entheses involvement, as it is shown to be a more sensitive tool. Our objective was to assess, by an ultrasonographic study, the entheses involvement in the widespread pain of patients with pSS.MethodsThis is a prospective study including 25 women with pSS and 25 age and sex matched healthy controls. An ultrasound examination, using grey scale and Doppler US, of five enthesitic sites (distal quadricipital, proximal patellar, distal patellar, distal Achillian and distal brachial tricipital) sought bilaterally the following lesions: hypoechogenicity, thickening, loss of fibrillar structure, erosions, enthesophytes, calcifications or Doppler hypervascularisation. A final score was calculated by summing the abnormalities scores of all entheses.ResultsThe mean age was 53.2 ± 11.3 years in the pSS group and 50.6 ± 9.7 years in the control group. The mean number of pathological entheses on ultrasound was 3.92 ± 1.93 in the pSS group versus 4.52 ± 2.27 in the control group (P > 0.05). The total score for enthesitis abnormalities was 4.96 ± 2.59 versus 5.72 ± 2.92 (P > 0.05), respectively. There was a positive correlation between total score of ultrasound enthesitic abnormalities and age in both groups.ConclusionIn patients with pSS, clinically painful sites were more frequently found than in US. Musculoskeletal pain was not due to enthesitis.     

IgA肾病湿热证与肾穿刺活检病理组织关系的临床研究

目的：研究IgA肾病湿热证与肾穿刺活检病理组织的关系。方法：每例肾穿刺活检病理组织均经光镜，酶标检查。结果：全病程的湿热总分与肾小球病变度、小管间质病变度、系膜增生度、免疫沉积度呈显或非常显等级相关；肾穿时的湿热证分值与肾小球病变度、系膜增生度、免疫沉积度无显相关。结论：(1)IgA肾病中，湿热影响IgA肾病的病理过程，加重肾脏的损害，进而影响预后及转归。(2)肾小管间质损害与湿热证的发生同步。湿热证时肾脏细胞因子和炎症因子活跃造成了小管和间质的急性损伤。(3)肾小球的损害与湿热证不同步，有时间上的相对滞后，反映了免疫复合物的产生和在肾脏局部的堆积而引起肾小球损害需要一定的时间。     

Report on intensive treatment of extracapillary glomerulonephritis with focus on crescentic IgA nephropathy

PURPOSE AND DESIGN OF STUDY.: In this retrospective analysis the effects of combined treatmentwith steroid pulses, cyclophosphamide and plasma exchange onsix crescentic IgA glomerulonephritis (IgAGN) patients, selectedon a histological basis, were examined. The histological criteriaincluded involvement of more than 40% of glomeruli by cellularcrescents. The effects of this treatment were compared to thoseobserved in three untreated crescentic IgAGN patients and 12treated patients who had extracapillary glomerulonephritis ofdifferent origins, i.e. ANCA-associated systemic or renal-limitedvasculitis. All patients, except the three crescentic untreatedIgAGN patients, received the same 2-month treatment accordingto a standardized protocol: steroid boli 15 mg/kg methylprednisolonefor 3 consecutive days by intravenous infusion, followed byprednisone per os (1 mg/kg/day for 4 weeks, 0.75 mg/kg/day for4 more weeks), cyclophosphamide per os 2.5 mg/kg/day for 8 weeks,and plasma exchange. RESULTS.: After this 2-month course of therapy, substantial clinical improvementwas observed in both IgAGN and vasculitis patients. However,a second biopsy revealed that florid crescents persisted inIgAGN patients and, unlike the vasculitis group, during thelong-term the initial clinical amelioration disappeared in one-halfof the treated IgAGN cases. Nevertheless, even in the progressivecases, intensive treatment seemed to substantially delay theonset of dialysis. CONCLUSIONS.: Despite some clinical benefits of therapy, short-term reversalof active crescents appears less likely to occur in crescenticIgAGN than in vasculitis-associated crescentic GN. Intensivetreatment seems sufficient to arrest, but inadequate to reverse,phlogistic lesions in IgAGN before development of chronic changes.     

The risk of Sjogren's syndrome in the older adults with gout: A medicare claims study

ObjectivesIn the absence of previous studies, our objective was to assess whether gout was associated with an increase or decrease in the risk of Sjogren's Syndrome (SS) in older adults, 65 years or older.MethodsWe used the 5% Medicare claims from 2006–2012. A multivariable Cox regression model assessed the association of gout with incident SS adjusting for age, sex, race, Charlson–Romano comorbidity index, and the use of medications for cardiovascular diseases (statins, beta-blockers, diuretics, ACE-inhibitors) and gout (allopurinol, febuxostat). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated.ResultsThere were 3,186 new cases of SS in the study cohort with crude incidence rates of SS of 30/100,000 person-years in patients without gout and 49/100,000 person-years in patients with gout. Multivariable-adjusted analyses showed that gout was independently associated with a higher hazard ratio of SS of 1.73 (95% CI, 1.45, 2.06). Sensitivity analyses that substituted continuous Charlson–Romano comorbidity index score with categorized score (model 2) or individual comorbidities plus three common cardiovascular diseases (hypertension, hyperlipidemia, and coronary artery disease; model 3), confirmed the main study findings with minimal attenuation of hazard ratio, 1.70 (95% CI, 1.43, 2.02) and 1.48 (95% CI, 1.25, 1.77), respectively. Younger age, female sex, White race and higher comorbidity score were associated with a higher hazard of SS.ConclusionsGout was associated with more than 1.7-fold higher risk of incident SS in adults 65 years or older. This finding needs to be reproduced and the underlying mechanisms for this association need further study.     

Clinicopathological analysis of Sjogren's syndrome complicated with ANCA associated vasculitis with renal involvement

Objective To investigate the clinical and pathological features of patients with a combination of Sjogren's syndrome (SS) and antineutrophil cytoplasmic antibody (ANCA) associated vasculitis with renal involvement. Methods By searching the Peking Union Medical College Hospital medical database and literature between January 1990 and June 2017, patients had a combination of SS and ANCA associated vasculitis with renal involvement were included. Data of clinical information, autoimmune antibodies, renal manifestations and renal pathology were retrieved and analyzed. Results Eighteen patients were enrolled: 4 from our hospital and 14 from literature. SS was diagnosed no later than ANCA associated vasculitis in all the patients, among which 83.3%(15/18) of patients had extra-glandular and extra-renal organs involved. All the patients were tested positive for myeloperoxidase (MPO)-ANCA, and only two were protein 3 (PR3)-ANCA positive concurrently. The positivity rates of antinuclear antibody (ANA), rheumatoid factor (RF), anti-SSA antibody, and anti-SSB antibody were 83.3%(15/18), 55.6%(10/18), 77.8%(14/18), and 38.9%(7/18), respectively. The renal manifestations were characterized by renal insufficiency with a median serum creatinine of 174 μmol/L, hematuria, moderate proteinuria with a median 24 hour urine protein of 1.70 g, and necrotizing vasculitis with oligo-immune complex and varying degrees of interstitial damage in pathology. Conclusions A combination of Sjogren's syndrome and ANCA associated vasculitis with renal involvement is rare in clinical setting, and almost all of the patients are MPO-ANCA positive, with high probability of ANA positivity and extra-glandular involvement. Physicians should beware of ANCA associated glomerulonephritis in SS patients with inexplicable renal dysfunction and renal biopsy should be carried out in time.     

基于药物反证的IgA肾病血瘀证血清蛋白组学研究

目的：应用表面增强激光解吸/电离飞行时间质谱技术（SELDI-TOF-MS技术）检测IgA肾病血瘀证患者活血化瘀药物治疗前后血清蛋白质指纹图谱的变化,分析与活血化瘀疗效相关的蛋白质指纹图谱,从蛋白质水平研究IgA肾病血瘀证血清的标志物.方法：采集于2012年1月～2012年10月肾内科住院的IgA肾病血瘀证患者10例,研究患者血清蛋白质指纹图谱,比较活血化瘀药物水蛭治疗前后IgA肾病血瘀证患者血清蛋白质指纹图谱变化,分析与活血化瘀疗效相关的蛋白质指纹图谱.结果：（1）10例IgA肾病血瘀证患者服药前后血清蛋白质指纹图谱数,经分析后检测到15个蛋白质峰差异具有统计学意义（P＜0.05）,发现M/Z为3 249.02、8 567.20、8 713.48的蛋白峰经治疗后明显下调,结合手动筛选和组间方差分析,发现M/Z为8 713.48的蛋白峰下调有意义.（2）10例IgA肾病血瘀证患者服药前后血瘀证积分比较,发现服药后积分较服药前明显下降（P＜0.05）,服药前（2.5±1.08）分,服药后（1.2±0.78）分.结论：M/Z为8 713.48的蛋白峰可能是IgA肾病血瘀证的血清蛋白标志物,通过调节M/Z为8 713.48蛋白峰,可能是水蛭治疗IgA肾病血瘀证的分子基础.     

IgA肾病血瘀证血清蛋白组学的初步研究

目的：应用表面增强激光解吸/电离飞行时间质谱技术（SELDI-TOF-MS技术）检测IgA肾病患者的血清蛋白质指纹图谱,试图寻找IgA肾病血瘀证相关的差异蛋白质,从蛋白质水平探索IgA肾病血瘀证血清的标志物.方法：采集于2011年10月～2013年2月肾内科住院的IgA肾病患者的血液样本共30例（血瘀证14例,非血瘀证16例）,同时采集健康人血液样本15例.研究各组病例血清蛋白质指纹图谱,所有蛋白质质谱采用Biomarker Wizard分析之后用Biomarker Patterns Software软件识别IgA肾病血瘀证特异表达的蛋白质,并建立证候决策模型.结果：（1）IgA肾病血瘀证患者与正常人血清蛋白质指纹图谱数据比较,经分析检测到30个蛋白质峰差异具有统计学意义（P＆lt;0.05）.（2）IgA肾病血瘀证患者与非血瘀证患者血清蛋白质指纹图谱数据比较,经分析检测到42个蛋白质峰差异具有统计学意义（P＆lt;0.05）.（3）IgA肾病血瘀证差异表达蛋白峰的筛选及证候决策模型的建立.经筛选质荷比为1 092.71（低表达）、1 972.32（低表达）、2 687.74（低表达）、3 196.19（高表达）、3 249.02（高表达）、8 567.20（高表达）、8 713.48（高表达）的7个蛋白峰组成的证候决策模型能很好区分IgA肾病血瘀证,该模型的敏感性为92.85%,特异性为93.75%,进一步对决策模型进行盲法验证,此模型对血瘀证的诊断敏感性为85.71%,特异性为81.25%.结论：M/Z为1 092.71、1 972.32、2 687.74、3 196.19、3 249.02、8 567.20、8 713.48的7个蛋白峰可能是区分IgA肾病血瘀证与非血瘀证的血清蛋白标志物.     

Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial

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