狼疮肾炎血栓性微血管病变的临床病理特点及预后

目的 探讨狼疮肾炎（LN）伴血栓性微血管病变（TMA）的临床病理特点、分型及预后。 方法 选取2000年1月-2009年2月期间在北京协和医院接受肾活检、病理诊断为TMA的SLE病例,根据病理上免疫复合物的多寡进一步分为富免疫沉积型TMA（35例）和寡免疫沉积型TMA（25例）。回顾性分析TMA总体和2种亚型各自的临床、病理和预后特点。 结果 （1）LN中TMA的发生率为9.2%（62例/675例）;表现为严重高血压、血肌酐明显升高、贫血和血小板减少;预后差,死亡及终末期肾病发生率25.0%,病死率13.6%。（2）LN伴TMA血管病变根据病理上免疫复合物的多寡可分为2个亚型即富免疫沉积型和寡免疫沉积型,富免疫沉积型临床和病理表现更活跃,但对激素+免疫抑制剂治疗的反应优于寡免疫沉积型,二者出现死亡及终末期肾病的比例分别为8.8%和32.0%。 结论 TMA在LN中并不罕见,该类患者病情重、预后差。LN伴TMA可能存在富免疫和寡免疫沉积2种亚型,进行这种分型的意义在于二者的预后明显不同,寡免疫沉积型对激素和免疫抑制剂的治疗反应差。     

Study of 25-OH vitamin D3 in patients with lupus nephritis and its association with disease activity

Objective To explore the level of 25-OH vitamin D3 in patients with lupus nephritis (LN) and its association with the activity of disease. Method Clinical data of 154 patients with lupus nephritis in our hospital from January 2008 to May 2015 were collected. Another 63 healthy adults were recruited as normal controls. Results The level of 25-OH vitamin D3 in patients with LN was significantly lower than that in normal controls (P﹤0.01). The concentration of serum 25-OH vitamin D3 was negatively correlated with 24 h urinary protein (r=-0.18, P=0.02), antinuclear antibody (r=-0.20, P=0.01), SLEDAI scores (r=-0.20, P﹤0.01), while positively correlated with serum complement C3 (r=0.32, P﹤0.01). The'full-housed' patients with all 5 antibodies positive in renal biopsy had lower level of 25-OH vitamin D (P＜0.05). Conclusion The level of 25-OH vitamin D3 in patients with LN is inversely correlated with the disease activity.     

Outcome in African-American children of neuropsychiatric lupus and lupus nephritis

The present study reviews the course of lupus nephritis (LN) with the added complication of neuropsychiatric systemic lupus erythematosus (NPSLE) in a predominantly African-American population in order to identify the risk factors accounting for the increased morbidity and mortality in African-American children. Previous studies, including those at our center, have demonstrated the poor prognosis for African-American children with LN. A possible factor is the involvement of the central nervous system (CNS), resulting in a heightened risk of morbidity, although to date there are no reports suggesting an association between NPSLE and patient and renal survival in children with lupus nephritis. To this end, we retrospectively analyzed charts of 72 children with lupus nephritis seen at our center from 1965 to 1999. These 72 patients formed two groups, with group 1 consisting of patients with lupus nephritis and NP manifestations and group 2 only lupus nephritis. We then examined various demographic factors such as age, sex and race along with the histopathologic class of lupus nephritis, occurrence of hypertension, incidence of end stage renal disease (ESRD), time to ESRD and mortality in both groups with the aid of Fisher’s exact t-test and the chi-square test. Briefly, the results revealed significantly higher class III or IV histopathologic lesions on biopsy, incidence of hypertension, progression to ESRD and mortality in children with NPSLE and LN (group 1) compared to LN alone (group 2) in spite of aggressive immunosuppressive therapy. In conclusion, we report that NPSLE with LN is associated with an increased rate of ESRD and mortality in our predominantly African-American children. Received: 26 March 2001 / Revised: 13 August 2001 / Accepted: 13 August 2001     

Outcomes in renal transplant recipients with lupus nephritis: experience at a single center

Background: The long-term prognosis of renal transplant recipients with systemic lupus erythematosus is still controversial. The outcome of these patients depends on the population studied, race/ethnicity, socioeconomic conditions, donor-related factors and recurrent lupus nephritis (LN), among other factors. Objective: This study was conducted to evaluate kidney transplantation outcomes for adult Brazilian patients with LN at a single center. Subjects and method: The archival records of all patients with LN who had received a kidney transplant at Santa Casa of Sao Paulo Hospítal were reviewed. Kaplan–Meier method was used to determine the survival rate. Results: We identified 18 patients with LN subjected to 22 kidney transplants during the 20-year interval. Two patients received three renal grafts. The majority of the patients were female, with 33.7 ± 10 years at the time of the transplantation, and half of them were African descendants or mixed. Sixteen transplants were performed from deceased donors and six from living-related donors. The patient survival rate was 90%, and graft survival was 68% at 10 years. Chronic allograft nephropathy was the major cause of graft loss. Two patients developed extra-renal manifestations of lupus. There was no clinical or histological evidence of recurrent LN. Conclusion: Renal transplantation is a method which can provide a long-term survival for patients with SLE and end-stage renal disease.     

狼疮肾炎与基质金属蛋白酶-9表达的相关分析

目的探讨狼疮肾炎（LN）与基质金属蛋白酶-9（MMP-9）及金属蛋白酶组织抑制因子-1（TIMP-1）表达的相互关系。方法采用逆转录-聚合酶链反应（RT-PCR）方法检测17例LN患者和22例无明显肾损害（24h尿蛋白定量〈500mg）的系统性红斑狼疮（SLE）患者外周血单个核细胞MMP-9mRNA和TIMP-1mRNA的表达水平。结果17例LN患者MMP-9／β-actin与TIMP-1／β-actin比值分别为（0．94±0．16）和（0．78±0．49）,与22例无明显肾损害（24h尿蛋白定量〈500mg）的SLE患者比较,其MMP-9 mRNA表达水平显著升高,具有统计学差异（P〈0．01）,但TIMP-1 mRNA表达水平无明显差异（P〉0．05）。结论LN患者MMP-9的异常表达可能与其肾脏病理损伤有关。     

一种狼疮性肾炎的临床活动性指数

筛选与狼疮性肾炎疾病活动程度相关性最好的临床与实验室指标，并建立一种疾病活动性的计分方法。方法以临床医师的判断作为疾病活动程度的外部标准，对１１７例狼疮性肾炎患者的资料进行单因素相关分析和多元回归分析。结果筛选出１４个最能提示疾病活动性的参数，并以各参数在多元回归分析中的回归系数作为其各自的加权分（略加简化），建立了一种狼疮性肾炎疾病活动程度的计分方法，即活动性指数。结论这一活动性指数能较简便、合理、有效地测定狼疮性肾炎的活动程度。     

Functional MR imaging of kidneys in patients with lupus nephritis

Objective To evaluate the functional magnetic resonance (MR) imaging in the assessment of renal involvement and pathological changes in patients with lupus nephritis (LN). Methods Seventeen patients with LN and 10 healthy controls underwent coronal echo?planar diffusion?weighted (DW) MR imaging and blood oxygen level dependent (BOLD) MR imaging of the kidneys with a single breath?hold time of 16 s. The apparent diffusion coefficient (ADC) and R2* value of the kidneys were calculated with high b values (b=500 s/mm2). The correlation between the renal injury variables and the ADCs or R2* values was evaluated. Results The mean ADC value of kidneys in patients with LN was (2.43±0.24)×10-3 mm2/s, the mean R2* values of the renal cortex and medulla were (11.72±2.35)/s and (13.07±2.35)/s respectively, which were all significantly lower than those in volunteers (P=0.045,P=0.048 and P=0.001, respectively). In the patients with LN, the mean ADC values were positively correlated with estimated glomerular filtration rate (eGFR) (r=0.558, P<0.05). There was a negative correlation between the ADC values of the right kidneys and pathological chronic indexes (r=-0.493, P<0.05). Moreover, the R2*values of the renal medulla were negatively correlated with 24 hours proteinuria, serum creatinine, pathological active indexes. The patients were assigned to group A (class Ⅲ, Ⅳ, Ⅴ, n=8) and group B (class Ⅴ+Ⅲ and Ⅴ+Ⅳ, n=9). The tubulointerstitial lesions in group B were more severe than those in group A, while the mean ADC values and R2* values of the renal cortex in group B were lower as compared to group A. Conclusion DW MR imaging and BOLD MR imaging may be used to non?invasively monitor the disease activity and evaluate the efficacy in lupus nephritis.     

狼疮性肾炎患者的妊娠结局探讨

目的探讨狼疮性肾炎（ＬＮ）患者的妊娠结局。方法对我院３２年间１６例ＬＮ患者２３次妊娠的处理结果进行分析归纳。结果ＬＮ活动时９３．３％的妊娠为治疗性终止妊娠，ＬＮ持续缓解时８７．５％的妊娠为成功妊娠且安全分娩。结论ＬＮ活动时应避免妊娠和终止妊娠，ＬＮ持续缓解时可允许妊娠和安全分娩     

环磷酰胺代谢酶基因多态性与中国汉族难治性狼疮肾炎的相关性

目的探讨中国汉族难治性狼疮肾炎(LN)和环磷酰胺(CTX)代谢酶基因多态性的相关性。 方法对2012年1月至2015年12月在海口市人民医院初发系统性红斑狼疮(SLE)的132例患者进行分析,其中LN组88例,非LN组44例;LN组中难治性LN 46例,非难治性LN 42例。比较各组临床指标差异。采用PCR-RELP检测CTX代谢酶基因,采用单因素方差分析CYP2C19*2、CYP2C19*3、CYP2B6*4、CYP2C9*3和CYP3A5与LN及难治性LN、非难治性LN的相关性。 结果(1)CYP2C19*2、CYP2C19*3、CYP2B6*4和CYP3A5频率分布符合Hardy-Weinberg平衡分布;(2)LN组较非LN组,血肌酐(Scr)(t＝2.68,P＝0.008)和SLEDAI明显升高(t＝4.07,P≤0.001),血红蛋白(Hb)(t＝－2.368,P＝0.019)和血白蛋白(ALB)(t＝－4.514,P＝0.000)明显降低,差异具有统计学意义;(3)单因素方差分析显示LN组CYP2C19*3 GC携带者与CC、GG携带者比较血尿素氮(BUN)显著升高[(13.3±13.02)mmol/L与(6.57±5.22)mmol/L与(7.08±6.11) mmol/L,F＝5.770,P＝0.004];难治性LN组中,GC携带者较CC、GG携带者Scr显著升高：[(436.22±286.38)μmol/L与(161.7±144.33)μmol/L与(66±19.02)μmol/L, F＝8.411, P＝0.001]差异均有统计学意义;(4) CYP3A5*3 GG携带者肾脏受累明显增多(χ²＝6.991,P＝0.03);在难治性LN组中CYP3A5*3 GG基因型Scr较高(F＝0.213,P＝0.81)但差异无统计学意义。 结论CTX代谢酶CYP2C19*3基因多态性对中国汉族难治性LN的疗效可能有影响,GC携带者疗效更差;CYP3A5*3 GG基因型携带者的肾脏受累更多见。     

Association of FCGR3B gene copy number variations and lupus nephritis in Henan Han populations

Objective To evaluate the copy number variation of FCGR3B gene in Henan Han systemic lupus erythematosus (SLE) patients and healthy controls, and explore the association between FCGR3B gene copy number variants (CNVs) and lupus nephritis (LN) susceptibility in Henan Han population. Methods FCGR3B CNVs was investigated in 142 SLE patients with nephritis, 187 SLE patients without nephritis and 328 healthy controls. A modified methodology based on competitive PCR named Multiplex AccuCopyTM Kit was used to detect FCGR3B copy number. Clinical and laboratory data were collected retrospectively from the medical record. Logistic regression analysis was used to determine the association of FCGR3B copy number variants with LN susceptibility. Rank correlation was used to determine the correlations between FCGE3B copy number variants and clinical phenotypes of LN. Results No significant difference was detected in the copy number variations of FCGR3B in different groups. Low copy number of FCGR3B was more commonly seen in patients with nephritis (P=0.042), and was a risk factor for LN (OR=2.059; 95% CI: 1.081-3.921; P=0.028). However, high copy number (＞2) had no effect on SLE patients without nephritis(OR=1.152; 95%CI: 0.711-1.866; P=0.565) and LN patients (OR=0.838; 95%CI: 0.529-1.329; P=0.454). There were no associations between FCGR3B copy number variants and clinical phenotypes and immunologic characteristics of LN. Conclusion The low copy number of FCGR3B is a risk factor for LN in Henan Han population.     

狼疮肾炎患者肾组织血管病变与预后的关系

目的 探讨狼疮肾炎患者肾组织血管病变与临床表现及预后的关系。 方法 总结1998年1月至2006年2月间，在北京协和医院接受B超引导下肾脏穿刺的系统性红斑狼疮（SLE）患者的肾脏病理及临床资料。根据肾脏血管病变性质，将患者分为无血管病变型 （NVL）、免疫复合物沉积型(ICD）、狼疮血管病型（LV）、血栓性微血管病型（TMA）、血管炎型（VAS）和动脉硬化型（AS）6类。比较各型血管病变的病理特点、临床表现及预后。回顾性分析肾脏血管病变与患者临床表现及预后的关系。 结果 （1）451例病理资料中，247例（54.8%）存在不同类型的血管病变，其中AS型132例（29.3%），LV型44例（9.8%），ICD型38例（8.4%），TMA型30例（6.7%），VAS型3例（0.7%）。（2）Ⅳ型狼疮肾炎中血管病变的发生率高于其他各型，达69.7%。（3）除ICD型外，其他各型血管病变中高血压的发生率均高于无血管病变组（P < 0.05）；平均Scr水平也高于无血管病变组（P < 0.05），其中TMA型高血压发生率（76.7%）、平均Scr水平[（195.4±180.3） μmol/L]最高，与LV型、AS型间差异有统计学意义（P < 0.05）。TMA型贫血和血小板下降的发生率也高于其他各组。（4）TMA型的预后最差，2年肾脏生存率为50%，其他各组的预后差异无统计学意义。 结论 血管病变在狼疮肾炎患者中常见，其中TMA型病情重，预后差；除ICD型外，其他血管病变型也存在不同程度的血压和Scr水平的升高，但各组预后差异无统计学意义。     

Lupus vasculopathy combined with acute renal failure in lupus nephritis

Several risk factors have been associated with the prognosis of lupus nephritis. However, few studies have focused on renal vascular lesions (such as thrombi due to immune complexes) as a prognostic factor in this disease. Here we present a case of systemic lupus erythematosus (SLE) in a 12-year-old girl who exhibited acute renal failure and severe hypertension on admission. Renal pathology findings included diffuse proliferative glomerulonephritis (class IVb) and lupus vasculopathy (LV) with immune complex deposition within glomerular capillaries and the preglomerular arteriolar lumen. Her clinical condition deteriorated rapidly, even after cyclophosphamide and methylprednisolone pulse therapy. It improved after 5 days of plasmapheresis and remained stable for up to 6 months under regular treatment. We suggest that renal biopsy performed early in SLE patients with renal involvement should be studied carefully for the presence of vascular lesions. Additionally, plasmapheresis can be considered in patients with LV refractory to other modalities of therapy.     

狼疮肾炎治疗目标的研究

目的探讨狼疮肾炎的治疗目标。方法３２例狼疮肾炎患者进入研究,其中２７例接受肾活检。治疗分为三期：（１）首始治疗期;（２）持续治疗期;（３）维持治疗期。制定数个等级的治疗缓解目标并追踪（４８±１０）月。结果２０／３２例患者达完全缓解,Ｓｃｒ从（３５３±１１５）降至（１１０±７６）μｍｏｌ／Ｌ（Ｐ＜０００１）,尿蛋白从（８６±４５）减少至（１５＋０９）ｇ／ｄ（Ｐ＜００１）。９例复发（２８１％）。至追踪期末,有２例分别进入氮质血症期和尿毒症期。结论狼疮肾炎的治疗目标是达到最大的治疗利益和最少药物副作用之间的平衡。要求达到实验室和临床的完全缓解是不现实的,应注意避免过度治疗带来的各种危险的副作用。     

Withdrawal of therapy in patients with proliferative lupus nephritis: long-term follow-up.

BACKGROUND: Whether corticosteroid and immunosuppressive therapy may be safely withdrawn in patients with proliferative lupus nephritis is still unclear. METHODS: In 32 patients with biopsy-proven proliferative lupus nephritis previously put into remission, therapy was gradually tapered off. RESULTS: When immunosuppressive therapy was stopped (median: 38 months; 25th-75th percentile: 24-81 months, after biopsy), 24 patients were in complete remission and eight had a median proteinuria of 1.05 g/24 h (25th-75th percentile: 0.91-1.1 g/24 h) with normal renal function. After stopping therapy, patients were followed for a median of 203 months (25th-75th percentile: 116-230 months). Fifteen patients (Group 1) never developed lupus activity. The other 17 patients (Group 2) developed lupus exacerbations in a median of 34 months (25th-75th percentile: 29-52 months) after stopping therapy and were re-treated. The only significant differences between the two groups were the longer median durations of treatment, 57 months (25th-75th percentile: 41.5-113.5 months) vs 30 months (25th-75th percentile: 18-41 months; P<0.009), and remission, 24 months (25th-75th percentile: 18-41) vs 12 months (25th-75th percentile: 7-20 months; P<0.02), before stopping therapy in Group 1 than in Group 2. At last follow-up, 12 patients of Group 1 were in complete remission, two had mild proteinuria and one had died. In Group 2, one patient died, 14 were in complete remission, one had mild proteinuria and in another patient serum creatinine doubled. CONCLUSIONS: Some patients with severe lupus nephritis who enter stable remission can be maintained without any specific treatment for many years. Those patients who have new flares can again go into remission with an appropriate treatment. The longer the treatment and remission before withdrawal, the lower the risk of relapse.     

Epstein-Barr virus-associated hemophagocytic syndrome in a patient with lupus nephritis

Hemophagocytic syndrome (HPS) is an unusual but severe illness associated with a variety of infections, as well as genetic, malignant tumors, and autoimmune diseases. We report an 11-year-old girl with systemic lupus erythematosus and nephritis who developed HPS associated with Epstein-Barr virus reactivation. In our patient, the onset of reactive HPS might be related to immunosuppressive treatment during the course of lupus nephritis.     

白细胞介素10基因多态性与系统性红斑狼疮和狼疮肾炎的关系

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TT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     

水蛭对系统性红斑狼疮性肾炎患者血浆内皮素和可溶性白介素-2受体的影响研究

目的探讨水蛭治疗系统性红斑狼疮（SLE）合并狼疮肾的机理。方法将44例SLE患者分为常规激素治疗组（20例）及常规治疗加水蛭干预组（24例）,观察治疗前后血浆内皮素（ET）及可溶性白介素-2受体（sIL-2R）浓度。结果治疗前血浆ET、sIL-2R水平均高于正常对照组（P〈0．01）,治疗后两者水平均显著改善（P〈0．05）,治疗后两治疗组比较,差异有统计学意义（P〈0．05）。结论在常规治疗基础上加用水蛭能更有效地改善SLE患者血浆ET、sIL-2R水平,从而减轻肾组织的损害。     

Assessment of lupus nephritis activity using urinary retinol-binding protein

We evaluated the presence of proximal renal tubular dysfunctionas measured by urinary retinolbinding protein (RBP) in 70 patientswith systemic lupus erythematosus. Renal disease activity wasassessed using the British Isles Lupus Assessment Group (BILAG)index. This is a clinical-laboratory score based on the principleof the physician's intention to treat. Increased urinary RBP(>400 jig/I) was detected in 17 of 22 (77%) patients withactive nephntis, six of 18 (33%) patients with probably activenephritis, one of nine (12%) cases with stable renal disease,and one of 21 (5%) cases without apparent renal disease (P<0.01).Compared to initial values, mean urinary RBP decreased significantlyin six patients evaluated after improvement of the exacerbationof renal disease. There was a positive correlation between urinaryRBP and 24-h proteinuria (r=0.40, P <0.01), and an inversecorrelation between urinary RBP and creatinine clearance (r=–0.60,P<0.0l). In a multivariate analysis adjusting for durationof disease, blood pressure, 24-h proteinuria, and creatinineclearance, mean urinary RBP continued to be significantly andprogressively greater for patients with no renal disease, stablerenal disease, probably active and active nephritis. Proximaltubular dysfunction is frequent in patients with active lupusnephritis. This association cannot be completely explained bythe effects of increased total proteinuria, reduced glomerularfiltration rate, and systemic hypertension. Urinary RBP seemsto be a marker of renal disease activity. This test may be clinicallyuseful to differentiate patients with active lupus nephritisfrom those with stable or absent renal disease.