狼疮肾炎患者肾组织CD134(OX40)表达的免疫组织化学分析

目的：了解狼疮肾炎(LN)肾组织中CD134(OX40)的表达并探讨其与LN肾脏病理改变和肾功能损害的关系。方法：用免疫组织化学方法对40例LN患肾组织CD134的表达进行检测，并对其与LN的肾脏病理改变和肾功能损害的相关性进行分析。结果：LN患肾组织中，CD134表达显上调，尤其以WHO Ⅳ型LN更为明显。除系膜细胞、内皮细胞和远曲小管CD134表达明显增强外，肾间质毛细血管和大血管内皮细胞亦有CD134表达阳性的浸润细胞。LN肾组织加以表达与LN肾脏病理活动指数和肾功能损害显相关。结论：LN患确实存在CD134共刺激分子的异常表达，这在LN的发生和发展中可能起着重要的作用。     

血管内皮细胞生长因子表达与狼疮肾炎肾脏病理的关系

研究发现血管内皮细胞生长因子(VEGF)有增加血管通透性、促进内皮细胞增殖、血管生成修复等功能。狼疮肾炎(LN)肾脏病理改变呈多样化,并多伴有肾脏微血管或小血管的损害。VEGF在LN的表达如何并在疾病转归上是否有一定作用,目前研究不多。我们对LN患者肾组织VEGF的表达进行了研究。一、对象与方法1.病例选择:LN患者40例,为1999年1月～2003年4月我院住院患者,其中男6例,女34例,平均年龄(30.6±12)岁。全部病例符合美国风湿病协会1982年系统性红斑狼疮(SLE)诊断标准,并有持续性蛋白尿超过0.5g/d或(和)管型尿,确诊为LN。按世界卫生组…     

霉酚酸酯治疗难治性狼疮性肾炎的临床研究

目的 :观察霉酚酸酯 (MMF)治疗难治性狼疮性肾炎 (LN)的疗效、副作用及停药后复发情况。方法 :对糖皮质激素和环磷酰胺治疗无效或复发的 2 6例难治性LN患者 (其中 2 1例病理诊断为Ⅳ型 )改用MMF联合中、小剂量糖皮质激素治疗。MMF治疗量为 1.0～ 1.5 g/d ,维持治疗量为 0 .5g/d ,治疗时间 3～ 12个月 ,平均 (7.4 9± 2 .84 )个月 ,11例治疗达 12个月后停药观察 6～ 2 0个月 ,平均 (13.2 3± 6 .32 )个月。结果 :经MMF治疗后 ,14例肾衰竭中有11例血清肌酐恢复正常 ,需透析的 3例也完全脱离透析。 76 .9%患者尿蛋白减少半量以上 ,34.6 %患者尿蛋白转阴 ,6 9.2 %患者血尿消失 ,84 .6 %患者血清抗ds-DNA转阴 ,92 .3%患者血清ANA转阴。未见明显的药物副作用。 11例停药后病情稳定 ,未再发狼疮活动。结论 :MMF对传统免疫抑制剂和糖皮质激素无效或复发的难治性LN ,尤其是Ⅳ型LN有独特的疗效 ,副作用小 ,停药后近期不复发     

霉酚酸酯对弥漫增生型狼疮性肾炎患者的疗效观察

目的 :比较霉酚酸酯 (MMF)和环磷酰胺 (CTX)冲击疗法治疗Ⅳ型狼疮性肾炎的疗效及不良反应。方法 :A组 2 0例 ,间断性CTX冲击疗法联合激素 1mg·kg-1·d-1治疗 ;B组 2 0例 ,MMF联合激素治疗。随访 12个月。结果 :CTX组、MMF组治疗LN均能降低蛋白尿、血尿 ,改善肾功能和免疫指标 ,两组无统计学意义 (P >0 .0 5 ) ,但MMF组治疗效果优于CTX组。不良反应 ,MMF组明显低于CTX组 (P <0 .0 5 )。结论 :CTX、MMF都能有效地控制狼疮性肾炎 ,且MMF具有一定的优越性     

霉酚酸酯对难治性肾病综合征和弥漫增殖性狼疮肾炎的疗效比较

目的 :观察霉酚酸酯 (MMF)在治疗原发性难治性肾病综合征与弥漫增殖性狼疮性肾炎的疗效比较。方法 :观察难治性肾病综合征 15例及同期弥漫增殖性狼疮性肾炎 (ⅣLN) 18例。以强的松 0 .4mg～ 0 .7mg·kg-1·d-1联合MMF1.0～ 1.5 2次 /d ,3～ 6个月后减半维持 1年 ,定期随访。结果 :以强的松联合MMF治疗 ,对ⅣLN疗效良好 ,完全缓解率达 10 0 % ,其中 3个月内缓解 12例 ,6个月内缓解 17例。而在原发性肾病综合征中 ,对MCD和MsPGN疗效良好 ,与ⅣLN相似 ,在MN中 2例完全缓解 ,3例仅部分缓解 ,2例无效。而后者均在 6～ 9个月间 ,对FSGS和MPGN仅 1例在 9个月后部分缓解 ,2例无效。结论 :MMF对MCD和MsPGN效果良好 ,对MN显示部分疗效 ,对FSGS和MPGN的疗效较差。总体上MMF对难治性肾病综合征的疗效逊于ⅣLN。     

肿瘤血管生成拟态分子机制及临床意义

血管生成拟态(VM)是指由恶性肿瘤细胞而非血管内皮细胞围成的、能为肿瘤提供血供的血管样通道性微循环模式.其发生与肿瘤细胞遗传学特征、血管结构自身特点及其微环境有关,其中蛋白分子EPHA2、VE-cadherin、PI3K、FAK、TrK、LN、MMP、TFPI等的生物学效应起着重要作用.VM分子机制为针对VM及VM与血管生成的联合治疗提供了靶点,为判定肿瘤预后提供了依据.     

重症狼疮肾炎的治疗

狼疮性肾炎(LN)是系统性红斑狼疮累及肾脏所引起的免疫复合物性肾炎,是临床常见的继发性肾小球疾病。重症LN是指狼疮活动期,多脏器严重受累,病情危重,矛盾较多,治疗难度较大,早期诊断,及时治疗至关重要。1重症LN的表现(1)肾病综合征;(2)肾功能不全(急进性、慢性);(3)狼疮脑病;(4)全身性血管炎;(5)严重感染(细菌、结核菌、病毒、真菌);(6)伴其他夹杂症(严重肝损伤、重型糖尿病);(7)肾脏病理:Ⅳ、Ⅴ、Ⅲ、Ⅲ+Ⅳ、Ⅲ+Ⅴ型LN,其中Ⅳ型多见,Ⅲ型较少。     

内源性肿瘤血管内皮生成抑素的研究进展

内源性肿瘤血管内皮生成抑素（Tumstatin）是近年发现的一种来源于基底膜Ⅳ型胶原α3，能特异性作用于肿瘤血管内皮细胞，抑制其蛋白质合成，而且不影响正常的血管内皮细胞。基于上述生物作用特点，该基因在肿瘤抗血管生成的分子靶向治疗研究中备受关注，并具有极大的应用前景。     

PDTC对缺氧/再给氧时血管内皮细胞ICAM-1,VCAM-1表达的作用

目的为研究心肌缺血-再灌注损伤的机制和治疗途径,检测血管内皮细胞缺氧/再给氧后细胞间黏附分子-1(intracellular adhesion molecule 1,ICAM-1)和血管细胞黏附分子-1(vascular cell adhesion molecule 1,VCAM-1)的表达,探讨抗氧化剂吡咯烷二硫氨基甲酸酯(pyrrolidine dithiocarbamate,PDTC)对血管内皮细胞表面细胞黏附分子表达的抑制作用.方法将培养的人胚肾血管内皮细胞分为3组,缺氧组:细胞经过缺氧/再给氧处理;PDTC组:在缺氧前于培养液中加入PDTC;对照组:未经处理.以多光子激光共聚焦显微镜分别检测3组细胞ICAM-1、VCAM-1的表达情况.结果对照组内皮细胞表面ICAM-1和VCAM-1呈较低表达,缺氧组呈较高表达;PDTC组ICAM-1和VCAM-1的表达明显低于缺氧组,但仍高于对照组.结论缺氧/再给氧促进内皮细胞活化,增强细胞黏附分子的表达,抗氧化剂PDTC能有效降低ICAM-1和VCAM-1的表达,为心肌缺血-再灌注损伤的治疗提供理论基础.     

血清同型半胱氨酸与狼疮性肾炎肾血管病变的相关性研究

目的:探讨狼疮性肾炎(LN)肾血管病变与血清同型半胱氨酸(Hcy)的相关性。方法:随机选取2010年1月1日~2013年10月1日在我院经肾穿刺活检确诊的105例LN患者及我院体检中心80例健康志愿者作为研究对象。将105例LN患者分为有血管病变组与无血管病变组,比较两组血清Hcy水平差异,并对血清Hcy与LN患者临床指标进行相关性分析。结果:105例LN患者血清Hcy水平为(13.83±6.37)μmol/L,而健康对照组为(8.78±3.12)μmol/L,两组比较,差异存在统计学意义(P0.01)。105例LN患者中无血管病变组48例,占45.7%;有血管病变组57例,占54.3%。其中动脉硬化型27例,免疫复合物型17例,非炎症坏死型6例,血栓性微血管病5例,血管炎型2例。无血管病变组血清Hcy水平为(10.15±3.07)μmol/L,而血管病变组血清Hcy水平为(16.91±7.03)μmol/L,两组比较差异存在统计学意义(P0.01)。本研究通过直线相关分析,结果显示血清Hcy与血肌酐、收缩压、舒张压呈正相关(P0.05);与24 h尿蛋白定量、三酰甘油、总胆固醇无明显相关(P0.05)。结论:血清Hcy与LN患者肾组织血管病变密切相关。Hcy水平与血肌酐、血压存在正相关。积极控制血清Hcy水平,对预防肾脏血管病变可能大有益处。     

正常人与原发性肾小球肾炎及狼疮性肾炎患者血尿IL-18水平比较

目的:探讨IL-18在原发性肾小球肾炎(PGN)及狼疮性肾炎(LN)发生、发展中的作用,以及寻找有助于两类疾病的鉴别诊断和对肾组织炎症活动程度进行评估的指标。方法:应用酶联免疫吸附检测(enzyme-linkedimmunosorbent assay,ELISA)法测定16例正常人、21例原发性肾小球肾炎(PGN)患者和18例LN患者血浆和尿液IL-18水平的变化。结果:LN患者血浆及尿液IL-18水平显著高于正常对照组(P均<0.001)和PGN组(P均<0.05),而且WHOⅣ型LN患者血浆及尿IL-18水平均明显高于非Ⅳ型LN患者(P<0.05);PGN患者尿液IL-18水平也高于正常人(P<0.05),但血浆IL-18水平与正常人比较无统计学差异(P>0.05);LN患者血浆IL-18水平与SLEDAI呈正相关(P<0.01),而尿IL-18水平与狼疮性肾炎RHSAI是密切正相关(P<0.001),但尿IL-18水平与血浆IL-18水平相关性没有统计学意义(P>0.05)。结论:IL-18参与LN的全身免疫病理过程,但可能仅参与PGN肾组织局部炎症过程;血浆IL-18检测可能有助于区分LN和PGN,尿IL-18的检测可望作为一项估计LN肾组织病变活动程度的有用指标。     

Urine biomarkers in juvenile-onset SLE nephritis

Over 80 % of patients with juvenile-onset systemic lupus erythematosus will have renal involvement compared to 40 % with adult-onset disease. Up to 44 % of children who do have lupus nephritis (LN) progress to renal failure in early adulthood. Improved methods of detecting onset of LN would allow earlier treatment, which may prevent irreversible renal scarring and a decline in renal function. Current conventional markers of disease activity fail to adequately predict renal lupus flares and include proteinuria, complement levels, anti-double-stranded DNA antibodies and serum creatinine concentrations. Standardized histological classification is currently the gold standard for diagnosing and classifying LN, but its invasive nature limits routine use for monitoring, especially in a childhood population. Novel biomarkers need to be sensitive and specific—and preferably non-invasive and cost-effective. The most promising biomarkers in juvenile-onset LN include urinary neutrophil gelatinase associated lipocalin, monocyte chemoattractant protein 1 and transforming growth factor-beta, although many others have been identified and are under investigation. No one biomarker yet discovered is unique to LN, indicating an overlap in disease pathophysiology. It is likely that a combination of biomarkers will be required for assessing disease flare detection, response to treatment and prognostic information. Potential biomarkers require longitudinal validation in large paediatric, prospective cohorts to assess their ability to act as clinically useful adjuncts.     

Investigation on the benefits of mycophenolate mofetil and therapeutic drug monitoring in the treatment of Japanese patients with lupus nephritis

Background

Mycophenolate mofetil (MMF) is recommended as a first-line immunosuppressant to treat lupus nephritis (LN). Prognosis and therapeutic response in LN are known to vary depending on race. We investigated the benefits of MMF and therapeutic drug monitoring (TDM) in the treatment of Japanese LN patients.

Methods

In this retrospective cohort study, a total of 20 patients with LN who started MMF treatment were included. Clinical data were collected regularly after MMF administration. We evaluated complete remission (CR) rate as the primary outcome. Predictors of CR were identified using univariate and multivariate analyses. In the research of TDM, the correlation with the area under the curve (AUC) was analyzed at MMF dose, single-point value, treatment response, and adverse events.

Results

Overall, 70% of cases showed CR; both flare-ups and refractory cases had favorable results. Cases of LN with nephrotic syndrome (NS) or class III/IV?+?V showed a significantly lower CR rate (p?<?0.005). The ratio of maintaining CR after MMF therapy was as high as 85.7%. In multivariate analysis, NS was an independent negative predictor of CR (HR 0.09, 95% confidence interval 0.01–0.81; p?=?0.03). The relationship between AUC and MMF dose was low, and AUC correlated with trough level (r?=?0.73). AUC tended to be high in the treatment responder (p?=?0.09), but did not correlate with adverse events of infection (p?=?0.92).

Conclusion

MMF is a beneficial treatment option for Japanese LN patients, and further investigation on TDM-based therapy is needed.

     

Mycophenolate mofetil treatment for therapy-resistant glomerulopathies

BACKGROUND: The management of steroid-resistant glomerulopathies remains a clinical problem. In this trial, we report a clinical observation of 43 patients treated with mycophenolate mofetil (MMF) for steroid-resistant glomerulopathies. METHODS: All patients underwent renal biopsies, and immunofluorescence and light microscopy examinations were conducted in all cases. All patients had been treated with prednisone at a dose of 1 mg/kg per day for at least 8 weeks. Of the 43 patients, 16 were treated with cyclophosphamide and five were treated with cyclosporine A before MMF started. The primary study outcomes were the change in the urinary protein excretion, serum creatinine, comparing the levels at the start of MMF treatment with those at the end of the MMF treatment period. Changes in renal function were also estimated with Modification of Diet in Renal Failure calculation. Wilcoxon signed-ranks test was used as appropriate to compare data from the start with data at the end of the treatment period. RESULTS: The primary glomerular diseases represented included membranoproliferative glomerulonephritis in 23.2%, membranous glomerulonephritis in 18.6%, IgA nephropathy in 13.9%, focal segmental glomerulosclerosis in 9.3%, lupus nephritis (systemic lupus erythematosus) in 25.6% and pauci-immune glomerulopathy in 9.3% of patients. The mean follow-up time was 28.9+/-12 months. Before MMF treatment, 16 patients (37%) had nephrotic range proteinuria and 11 (26%) had renal insufficiency. The urinary protein before MMF treatment was 3.3+/-2.6 g/dL (0.6-9.6) and decreased significantly to 0.87+/-1.1 g/dL (0-5.5) at the end of the MMF treatment period (P=0.02). During treatment, complete remission was seen in 27 patients, partial remission in 10 patients and MMF failure in six patients. The serum creatinine level decreased significantly from 1.29+/-0.55 mg/dL (0.6-3.0) to 1.14+/-0.38 mg/dL (0.5-2.4) post MMF therapy (P=0.046). Using the four-variable Modification of Diet in Renal Failure formula, the glomerular filtration rate increased from 71.5+/-28 mL/min per 1.73 m2 to 78.1+/-27 mL/min per 1.73 m2 (P=0.021). Renal insufficiency resolved in seven of the 11 (63.6%) patients with renal insufficiency initially, two with membranoproliferative glomerulonephritis, two with membranous glomerulonephritis, one with focal segmental glomerulosclerosis, four with pauci-immune glomerulopathy, two with systemic lupus erythematosus nephritis, and in two patients de novo renal insufficiency developed. CONCLUSION: In general, MMF was well tolerated, and most of the patients achieved remission and improvement of renal functions. MMF treatment appeared to offer benefits to problematic patients refractory to conventional therapies for glomerulopathies.     

Maintenance therapy with mycophenolate mofetil for children with severe lupus nephritis after low-dose intravenous cyclophosphamide regimen

Although recent studies on adults with lupus nephritis indicate that mycophenolate mofetil (MMF) may be effective in maintaining remission for patients who previously received short-term intravenous cyclophosphamide (IVCY) induction therapy, the experience with the new immunosuppressive agent in children with severe lupus nephritis has not been as satisfactory thus far. To assess the efficacy and safety of maintenance therapy with MMF, we prospectively analyzed four patients with biopsy-proven severe lupus nephritis (three girls, one boy; mean age 12 years; two with class IIIA, two with class IVG(A); mean duration of lupus nephritis 7 months) receiving MMF for at least 6 months after induction treatment. These patients had been treated previously with 6 months of low-dose IVCY combined with oral mizoribine and steroids for induction, followed by therapy with MMF adjusted to maintain predose mycophenolic acid (C0-MPA) levels at 2-5 mcg/ml. Mean follow-up after staring MMF was 27.5 months (range 6-41). The mean MMF dose required was 405 +/- 49 mg/m(2) per 12 h, which maintained mean C0-MPA levels of 3.3 +/- 0.41 mcg/ml. No patient experienced renal flares during maintenance therapy with MMF, which permitted a significant reduction in mean prednisolone dose from 11.9 +/- 1.3 to 3.9 +/- 2.6 mg/day (P = 0.003). No significant gastrointestinal or hematologic side effects of MMF were noted. This preliminary study demonstrates that maintenance therapy with MMF after a low-dose IVCY regimen appears to be a promising intervention without adverse effects in children with severe lupus nephritis. These data should be confirmed by a prospective randomized multicenter clinical trial.     

Role of RAS inhibitor in the treatment of lupus nephritis with thrombotic microangiopathy

Objective To investigate whether RAS inhibitors can improve renal function in the treatment of lupus nephritis (LN) with thrombotic microangiopathy (TMA). Methods A total of 15 LN patients with TMA proven by renal pathology, from January 2000 to December 2013 in PUMCH, were included. The serum creatinine (Scr) and blood pressure (BP) before and after using RAS inhibitors were analyzed. Results (1)Male/female ratio was 1∶14. All of the patients had renal dysfunction, and median peak value of Scr was 396 μmol/L (160～643 μmol/L). 5 cases (33.3%) required acute dialysis during hospitalization. Hypertension occurred in 15 patients, while 6 cases (40.0%) were diagnosed malignant hypertension. (2) Anemia and thrombocytopenia occurred in 15 and 14 cases, respectively. Three cases (20.0%) were diagnosed MAHA definitely and 5 cases (33.3%) were diagnosed MAHA probably. (3) Renal biopsy showed class Ⅱ in 1 case, Ⅲ in 4 cases, Ⅳ-(G) in 2 cases, IV(S) in 5 cases and IV+V in 3 cases. Active lesions were predominant in both glomeruli and renal vasculopathy. (4) All the patients received steroid and immunosuppressive therapy, of whom 9 cases were given steroid pulse therapy. Thirteen cases received cyclophosphamide, and the rest 2 cases received cyclophosphamide and mycophenolate. After steroid pulse therapy, there were only 5 patients (55.6%) who got decreased Scr. In 13 patients (86.7%), hypertension was ameliorated and Scr decreased within one week after implementing RAS inhibitors, which fell medianly 15.8% and 17.0%, respectively. (5) Eleven of the 15 patients were followed from 8 to 135 months (median 32 months), and the other 4 patients were lost. Five cases who was on dialysis during hospitalization became independent of renal replacement therapy, while the other cases also got improved renal function. Conclusions Patients of LN with TMA who develop AKI and refractory hypertension should be treated with RAS inhibitors. Improved renal survival and successful discontinuation of dialysis are possible benefits when RAS inhibitors are used to treat LN with TMA.     

Relationship between serum B-cell activating factor levels and clinicopathology in children with lupus nephritis

Objective To analyze the relationship between the serum B-cell activating factor (BAFF) levels and clinical characters and pathological features in children with lupus nephritis (LN). Methods ELISA was used to detect the serum BAFF (sBAFF) levels of the 54 LN children diagnosed in the First Affiliated Hospital, Sun Yat-sen University during October 1, 2014 to December 31, 2016 and with complete clinical data. According to whether glucocorticoid or immunosuppressive agents has been used at their first admission, patients were divided into treated group (n=44) and non-therapy group (n=10). According to the renal response after induction treatment for 6 months, patients were divided into remission group (n=20) and non-response group (n=34). According to whether there was renal recurrence, they were divided into recurrence group (6 cases) and non-recurrence group (48 cases). According to renal biopsy, patients were divided into class-Ⅲ, class-Ⅳ and class-Ⅴ group. Another 15 healthy children were taken as a control group. The correlations between sBAFF and clinical manifestation, laboratory examination, renal biopsy and clinical outcome were analyzed. Results (1) Compared with the control group, the sBAFF was significantly increased in LN group (t=3.821, P＜0.001). Compared with the non- neuropsychiatric systemic lupus erythematosus (NPSLE) group, sBAFF was significantly increased in NPSLE group (t=2.202, P=0.032). (2) Compared with that in treated group, sBAFF was significantly higher in untreated group (LSD-t=2.309, P=0.025). Compared with non-response group, sBAFF was significantly decreased in response group (LSD-t=2.035, P=0.046). (3) No significant difference was observed between class-Ⅲ, class-Ⅳ and class-Ⅴ pathological classification group (F=1.080, P=0.459). sBAFF in LN children was not significantly correlated with the active index (AI) or chronic index (CI) of Austin index (r=-0.273, P=0.063; r=0.150, P=0.314). (4) In LN children, sBAFF has positive correlation with ESR and IgG level (r=0.289, P=0.036; r=0.340, P=0.017) and negative correlation with WBC (r=-0.337, P=0.013). Multiple linear regression model showed that serum IgG level (β'=0.517, P=0.001) and renal response (β'=-0.271, P=0.037) were independent influencing factors of sBAFF level. Conclusions Renal remission and serum IgG levels in LN children are influencing factors of sBAFF levels. sBAFF is helpful to clinical assessment on renal response of LN children.     

Correlation between serum C3 and glomerular microthrombosis in patients with lupus nephritis

Objective To investigate the correlation between serum C3 and glomerular microthrombosis in patients with lupus nephritis (LN). Methods Patients who were diagnosed as LN by renal biopsy hospitalized in Department of Nephrology, the First Affiliated Hospital of Shenzhen University from January 2010 to February 2019 were retrospectively analyzed and they were divided into glomerular microthrombosis group (GMT group) and non-glomerular microthrombosis group (non-GMT group). The demographic data, clinical characteristics, pathology and prognosis of the two groups were compared. Logistic regression and smooth curve fitting of generalized additive mixed model analysis were used to explore the correlation between serum C3 and glomerular microthrombosis. Renal prognosis of the two groups were compared by the Kaplan-Meier survival curve. Results A total of 116 patients were enrolled, aged (32.79±11.43) years old, in which 108 cases (93.10%) were female. Thirty-seven patients (31.90%) were confirmed to be combined with GMT (GMT group) and 79 cases were not (non-GMT group). Compared with the non-GMT group, patients in the GMT group were relatively older (t=-2.876, P=0.002), with higher proportion of hypertension ( χ2=7.492, P=0.006)，higher urine protein quantitation (Z=-2.115, P=0.003), lower levels of eGFR and serum complement C3 (Z=3.469, P＜0.001; t=1.744, P＜0.001), higher systemic lupus erythematosus disease activity index (t=-2.758, P=0.007). As to the pathological characteristics, type IV LN patients were the majority (72.97%). Proportion of crescents and pathological activity indicators of the GMT group were higher (Z=-1.866, P=0.002; t=-5.005, P＜0.001), nuclear fragmentation, endothelial hyperplasia and renal tubular atrophy were more serious ( χ2=14.987, P＜0.001; χ2=15.695, P＜0.001; χ2=4.130, P=0.042). Multivariate logistic regression analysis indicated that serum complement C3 was a relational factor of the formation of GMT in LN patients (OR=0.966, 95％CI 0.938-0.995, P=0.023). Smooth curve fitting of generalized additive mixed model analysis indicated that level of complement C3 had a linear relationship with the changing trend of GMT. The Kaplan-Meier curve showed that there were statistical differences between the two groups in terms of complete remission of urine protein (Log-rank χ2=5.858, P=0.016) and doubled serum creatinine /end-stage renal disease (Log-rank χ2=3.945, P=0.047). Conclusions Serum C3 is closely related to the formation of GMT in LN patients, and statistical differences were demonstrated in the renal prognosis of GMT group and non-GMT group.     

Renal haemodynamic characteristics and their correlation with renal pathology in patients with systemic lupus erythematosus

SUMMARY: To clarify the characteristics of renal haemodynamics and their correlation with renal pathology in patients with systemic lupus erythematosus (SLE), renal function and renal biopsy findings from 101 SLE patients were analysed retrospectively. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were examined simultaneously. Filtration fraction (FF) was calculated from the values obtained for GFR and RPF (GFR/RPF). The GFR was low in one-third and within normal limits in two-thirds of class IV patients with lupus nephritis (LN). In contrast, high RPF was observed in half of class IV patients. As a result, over 70% of class IV patients possessed a very low FF (less than 15%). The sensitivity of very low FF for class IV LN was significantly higher than that of low GFR. In conclusion, low FF was frequently recognized, especially in patients with diffuse proliferative LN. Decreased FF was a highly sensitive indicator of diffuse proliferative LN. Thus, determination of renal haemodynamics, including FF, may be a useful clinical parameter for evaluating renal involvement in patients with SLE.     

Shedding of endothelial protein C receptor contributes to vasculopathy and renal injury in lupus: in vivo and in vitro evidence

BACKGROUND: Candidate biomarkers for vasculopathy in systemic lupus erythematosus (SLE) include circulating endothelial cells and the recently identified endothelial protein C receptor (EPCR) which, when shed, promotes a thrombotic diathesis. This study sought correlation between plasma levels of soluble EPCR and disease manifestation/severity, with a focus on lupus nephritis. METHODS: In 81 SLE patients (evaluated cross-sectionally and longitudinally) and 59 healthy controls, levels of soluble EPCR and soluble E-selectin were assessed by sandwich enzyme-linked immunosorbent assay (ELISA), circulating endothelial cells isolated by immunomagnetic separation, and EPCR gene polymorphisms determined. Mechanisms of vascular injury were addressed in vitro in human aortic endothelial cells (HAEC) cultured in the presence and absence of interferon-gamma (IFN-gamma). RESULTS: The mean level of soluble EPCR was significantly higher in SLE patients (263 +/- 13 ng/mL) than controls (174 +/- 11 ng/mL) (P < 0.0001). Patients with active or past renal involvement had significantly higher mean soluble EPCR levels (306 +/- 21 ng/mL) (N= 40) than patients without nephritis (228 +/- 14 ng/mL) (N= 41) (P= 0.0033). Mean soluble EPCR correlated positively with serum creatinine (R= 0.3429, P < 0.0001). The prevalence of the enhanced-shedding EPCR polymorphism A6936G was higher in SLE (41%) (N= 27) than controls (7%) (N= 29) (P= 0.0039). Patient and control plasma were also interrogated for soluble E-selectin, a comparator plasma marker. The results suggest that soluble E-selectin and soluble EPCR are not equivalent end points of vasculopathy and endothelial perturbation in SLE. Although in SLE patients the absence or diminished expression of membrane EPCR on circulating endothelial cells varied, the rare circulating endothelial cells detected in controls invariably expressed membrane-bound EPCR. IFN-gamma-treated HAEC expressed less membrane-bound EPCR [133 relative fluorescence units (rfu)] than untreated HAEC (275 rfu); more soluble EPCR was detected in IFN-gamma-treated (1.1 ng/10(6) cells) than untreated HAEC (0.65 ng/10(6) cells) (P= 0.027). CONCLUSION: The results obtained from this cross-sectional/longitudinal study support the hypothesis that the vascular dysfunction characteristic of SLE may be related to a dramatically altered distribution of EPCR, both soluble and membrane-bound forms.