弥漫增殖性狼疮性肾炎按血管病变为基础的病理分型探讨

目的：根据肾脏血管病变的特点，建立弥漫增殖型狼疮性肾炎的病理分型，评价其对判断病情，指导治疗及评价预后的意义。方法：根据肾活检病理肾小球毛细血管及间质血管病变特点第３４１例弥漫增殖型狼疮性肾炎为４组，弥漫增殖组（Ａ组１２８例）袢坏死组（Ｂ组８６例）袢坏死伴间质血管病变组（Ｃ组４８例），血栓形成组（Ｄ组７９例），回顾性分析各组患者临床表现，对不同免疫抑制治疗的的近期疗效及长期预后。结果：（１）四组患     

弥漫增生型狼疮性肾炎的远期预后

目的:回顾性分析弥漫增生型狼疮性肾炎(DPLN)的远期预后及影响预后的因素。方法:临床符合SLE,经肾活检存在弥漫增生性病变的狼疮性肾炎(Ⅳ/Ⅳ V,ISN/RPS2003肾脏病理分型标准)患者441例[女性377例,男性64例,平均年龄(29.6±9.85)岁]。通过Kaplan-Meier法估算人肾存活率,并建立COX风险模型,分析影响预后的危险因素。结果:(1)人、肾存活率:441例平均随访(60.8±43.3)个月(中位时间61个月)。共15例(3.4%)死亡(感染11例,脑血管意外2例,肺出血1例,猝死1例),5年、10年人存活率分别为96.5%和92%;共28例(6%)在随访期间进展至终末期肾病(endstageranaldisease,ESRD),5年、10年肾存活率分别为94.5%和86.4%。随访初SCr≥132.6μmol/L(HR6.54)、慢性化指数(CI)≥3(HR3.52)、伴有血管病变(HR10.37)及V型病变(HR2.80)、治疗未获缓解(HR10.22)及复发(HR6.13)是肾脏进入ESRD的独立危险因素。(2)1999至2003年DPLN患者5年人、肾存活率均高于1993至1998年(分别为96.3%vs93.6%;95.7%vs90%,P>0.05),但未达统计学差异;(3)复发及转型:323例(73.2%)在随访(7.6±8.5)月(中位时间5月)时达缓解,139例(31.5%)平均随访(35.4±28.2)月(中位时间26月)时复发,5年累积复发率达34.7%。71例因治疗未缓解或复发行重复肾活检,其中17例(23.9%)发生转型(Ⅳ型转为Ⅳ V型)。(4)并发症:共发生并发症270例次(61.2%),主要包括感染(21.3%),月经紊乱(20.2%),股骨头坏死(5.4%),肝酶升高(4.5%)等,5年累积无并发症发生率56.7%。结论:本组DPLN5年人肾存活率可达90%,但复发率及并发症发生率高。随访初合并血管病变、肾功能不全、肾组织慢性化损伤严重、治疗未缓解及复发进入ESRD风险增大。感染仍为主要死因。提高缓解率、降低复发率及减少并发症仍是重型LN临床研究重点。     

吗替麦考酚酯治疗弥漫增生性狼疮性肾炎的多中心临床研究

目的　多中心、前瞻性观察吗替麦考酚酯 (MMF)治疗弥漫增生性狼疮性肾炎的临床疗效和不良反应。方法　全国 9家医院共收集系统性红斑狼疮患者 75例 (男 1 3例 ,女 62例 ) ,均经肾活检确定为活动性弥漫增生性狼疮性肾炎 (LN IV) ,年龄 (31 0± 1 0 1 )岁 ,病程 (38 9± 52 5)个月 ;其中经正规激素联合环磷酰胺治疗无效者 2 6例 ,复发者 2 1例 ,初治患者 2 8例。治疗方案采用激素联合MMF。MMF起始剂量为 0 5～ 2 0g/d ,随访时间≥ 6个月。 38例治疗后行重复肾活检 ,并进行急性指数 (AI)、慢性指数 (CI)、免疫球蛋白 (Ig)及补体沉积半定量评分。结果　MMF平均起始剂量 (1 2 6±0 30 )g/d ,治疗 3、6个月时MMF平均剂量分别为 (1 2 1± 0 30 )g/d、(0 95± 0 33)g/d。治疗 3个月狼疮活动分数 (SLE DAI)由 1 6 9± 6 7降为 8 1± 4 8(P <0 0 1 ) ,血红蛋白由 (92± 2 1 )g/L升至 (1 1 2± 2 8)g/L(P <0 0 5) ,尿蛋白由 (4 2 4± 2 66)g/d降至 (2 1 8± 3 75)g/d(P <0 0 5) ,血清白蛋白升至 (35 3±6 9)g/L(P <0 0 1 ) ,肾功能明显改善 ,无活动性尿沉渣 ;治疗 6个月尿蛋白继续下降至 (1 54± 1 60 )g/d ,血红蛋白、血清白蛋白继续升高。血清A dsDNA抗体阳性及低补体血症患者比例显著降低。     

狼疮性肾炎的远期预后

本文对８６例随访初期肾功能正常，随访期在５年以上的ＬＮ患者的远期预后进行了分析评价。平均随访期８８．１２个月后，４７例患者临床缓解；１１例虽病情持续活动，但肾功能维持稳定；１８例肾功能轻￣中度减退。     

循环内皮细胞在狼疮性肾炎血管病变诊断中的应用

目的：检测狼疮性肾炎（LN）患者循环血内皮细胞（CECs），探讨其在肾脏血管病变的诊断和判断病情中的作用。方法：60例经肾活检诊断为LN患者，其中30例伴血管病变患者，30例不伴血管病变患者。正常对照为30名健康志愿者。抽取外周血，采用免疫磁珠分离方法计数CECs的数量，同时进行血清肌酐、尿蛋白和尿红细胞等临床项目检查。结果：不伴血管病变组LN患者CECs数目与正常对照组相比差异无统计学意义，伴血管病变组患者CECs数目显著高于不伴血管病变组和正常对照组（P〈0．01）。伴血管病变组患者CECs与血清肌酐水平呈正相关（r=0．513，P〈0．01）。在伴血管病变LN患者中，合并血栓性微血管病变（TMA）患者CECs数量明显高于不伴有TMA患者（P〈0．01）。结论：CECs检测不仅能反映LN患者血管病变的存在，而且还能作为判断血管病变严重程度的指标。     

Ⅳ型狼疮性肾炎伴血栓性微血管病变的临床特点及预后

目的:回顾性分析Ⅳ型狼疮性肾炎(LN)伴肾间质血管血栓性微血管病变(TMA)患者的临床、病理及预后。方法:33例在解放军肾脏病研究所住院、经肾活检诊断为Ⅳ型LN(参照2003年ISN/RPS分型方案)伴肾间质血管TMA病变的患者,女性27例,男性6例,平均年龄(31.8±10.9)岁,回顾性分析其临床特点(肾脏表现、肾外脏器受累、免疫学异常及病理特征)及预后特征(近期疗效、远期人、肾存活率及终末期肾衰发生的危险因素)。结果:(1)27例(81.8%)入院即表现为肾功能不全[SCr(274.0±176.8)μmol/L],其中14例(42.4%)需要肾脏替代治疗。高血压、肾病范围蛋白尿、肉眼血尿的比例分别为93.9%、57.6%和24.2%。(2)微血管病性溶血性贫血(MHA)比例为60.6%,神经系统损害、心、肺受累及浆膜腔炎的发生率分别为:18.1%、36.3%、15.1%和66.7%。(3)血清ANA、抗ds-DNA及抗心磷脂抗体阳性率分别为90.9%,75.8%和33.3%。96.9%和42.4%的患者伴有低C3及C4血症。(4)肾活检病理分型Ⅳ(G)型25例(75.8%)、Ⅳ Ⅴ型7例(21.2%)、Ⅳ(S)型1例(3.0%)。袢坏死、Fribin阳性的袢内血栓及新月体比例分别为:51.5%,69.7%和60.6%。20例(60.7%)肾间质小动脉有血栓形成。中-重度小管-间质慢性化损害者达78.8%。(5)患者中位随访时间为13月(1～101月),6例(42.9%)摆脱肾脏替代治疗,6月及12月治疗有反应率分别为38.9%和55.2%。死亡3例(感染、不明死因和多器官功能衰竭各1例),10例(38.5%)进展为终末期肾衰。患者1年、3年、5年人生存率分别为96.2%,69.2%和69.2%;肾存活率分别为:62.3%,62.3%和46.7%。结论:伴TMA的Ⅳ型LN患者肾脏损害严重,部分患者可无典型MHA表现,肾小球病理类型以Ⅳ(G)和Ⅳ Ⅴ型多见,Ⅳ(S)型少见,患者预后差。应加强LN伴TMA的早期诊断,探索有效的治疗手段。     

血栓调节蛋白检测在狼疮性肾炎血管病变中的意义

目的：探讨狼疮性肾炎(LN)患者血浆可溶性血栓调节蛋白(sTM)水平和肾组织TM免疫组化染色特点，分析其与系统性红斑狼疮活动度(SLEDAI)、血管病变、肾功能、蛋白尿、肾组织病理类型之间的关系。方法：60例经肾穿刺活检明确诊断的LN患者，采用酶联免疫吸附法(ELISA)检测血浆sTM水平，免疫组化染色检测肾小球和间质血管TM的表达。结果：Ⅱ型LN患者血浆sTM水平与正常对照组相近，Ⅳ型LN患者血浆sTM水平显著高于Ⅱ型LN；而合并有血栓性微血管病变的LN患者血浆sTM水平显著高于Ⅳ型LN，血浆sTM水平与狼疮的病变活动度和血清肌酐水平呈正相关，与蛋白尿多少无关。肾组织TM免疫组化染色示Ⅳ型LN肾小球与血管TM染色强度强于Ⅱ型LN；合并血栓性微血管病变LN患者肾小球与血管TM的染色强度与Ⅳ型LN相似。结论：血浆sTM水平与SLEDAI、血管病变轻重、肾功能损害程度及肾组织病变类型有关。肾小球和肾间质血管的TM表达强度与LN病理类型有关，但不能反映血管病变的轻重。血浆sTM水平不仅反映SLE疾病活动性，而且与LN的血管病变严重程度有关。血浆sTM水平可作为LN血管病变程度的指标，为指导治疗、判断预后提供依据。     

狼疮性肾炎肺胸膜病变的临床观察

系统性红斑狼疮（ＳＬＥ）是一种多系统、多器官受累的自身免疫性疾病。肾脏和肺胸膜常同时受累。本文对１５２例肺胸膜病变的狼疮性肾炎（ＬＮ）进行观察，现报道如下。１临床资料１１一般资料本文收集１９８４—１９９６年确诊为ＬＮ的住院病例５９１例，有肺胸膜病变...     

血清血管内皮细胞生长因子的表达与狼疮性肾炎的关系

目的　探讨狼疮性肾炎 (LN)患者血管内皮细胞生长因子 (VEGF)在血清浓度与系统性红斑狼疮 (SLE)活动与肾脏病理等的关系。方法　采用ELISA法对 3 2例LN患者血清水平进行检测 ,并结合临床资料及肾脏病理进行相关分析。结果　LN患者血清VEGF水平较正常人升高 ,(P <0 .0 5 ) ,但各型LN组间血清VEGF浓度比较无明显区别 ;血清VEGF的浓度与SLE疾病活动指数 (SLEDAI)呈正相关 (P <0 .0 5 ) ;血清VEGF水平与尿蛋白无相关性 (r =0 .185 ,P >0 .0 5 )。结论　LN患者血清VEGF的水平升高 ,血清VEGF水平与肾脏病理类型 (Ⅱ、Ⅳ、Ⅴ型 )无相关性 ;血清VEGF水平可反映SLE的疾病活动程度 ;LN患者血清VEGF水平对尿蛋白的量无影响     

狼疮性肾炎继发侵袭性肺曲霉病的临床特征及预后

目的：回顾性分析狼疮性肾炎(LN)患者合并侵袭性肺曲霉病(IPA)的临床特征及预后。方法：选取2008年9月至2022年1月国家肾脏疾病临床医学研究中心收治的LN合并IPA的22例患者,分析其临床资料及预后。结果：22例LN患者发病年龄35.6±15.6岁,LN病程4.5(3,51)月,诊断IPA前6月内平均接受3种免疫抑制剂。IPA首发症状多为发热、咳嗽、咳痰(72.7%),以烟曲霉最为常见。7例(31.8%)患者在IPA起病3月内死亡,死亡组患者IPA起病前6月内24 h尿蛋白定量、IPA感染时乳酸脱氢酶及狼疮活动性指标显著高于存活组,CD20⁺B细胞计数显著低于存活组,治疗期间出现混合感染、入住ICU、需要丙种球蛋白/升白细胞药物、气管插管机械通气、连续性肾脏替代治疗(CRRT)的比例更高(P<0.05)。5例患者在随访中进入终末期肾病。结论：LN患者继发IPA的危险因素复杂,狼疮活动及免疫功能低下者预后更差。     

Circulating thrombomodulin and vascular cell adhesion molecule-1 and renal vascular lesion in patients with lupus nephritis

Currently, the detection of renal vascular lesions (VLS) in lupus nephritis (LN) mainly depends on biopsy examination, and lack surrogate biomarkers for clinical dynamic evaluation. The aim of the present study is to explore the correlation between circulatory endothelial damage biomarkers and VLS. Soluble E-selectin, thrombomodulin (TM) and vascular cell adhesion molecule-1 (VCAM-1) were measured by ELISA. TM and VCAM-1 levels both were significantly elevated in LN with VLS than in LN without VLS (P < 0.01). However, the serum E-selectin was not significantly changed in LN patients with and without VLS. A positive correlation was found between TM and serum creatinine (r = 0.617, P < 0.05) in patients with vascular lesions. In order to further analyse the relationship between TM level and severity degree of vascular lesions in LN patients, we subdivided the patients with vascular lesions into two groups: with thrombotic microangiopathy (TMA) and without TMA. TM level of the patients with TMA is significantly higher than those without TMA (P < 0.01). In conclusion, combined with renal pathological examination, monitoring the circulatory levels of TM and VCAM-1, can provide circulating biomarkers of VLS in LN patients.     

Long-term renal outcomes of mesangial proliferative lupus nephritis in Chinese patients

Clinical Rheumatology - This study aimed to explore the long-term outcomes of mesangial proliferative lupus nephritis (LN class II) and the factors associated with its relapse and histological...     

Renal immunofluorescence and the prediction of renal outcome in patients with proliferative lupus nephritis

The risk for endstage renal failure in patients with proliferative lupus nephritis (PLN) depends largely on the severity and reversibility of the inflammatory process as determined by light microscopy (LM). As the intrarenal formation of immune complexes is thought to initiate this inflammation, we studied whether renal immunofluorescence microscopy (IFM) provides clinical or prognostic information in addition to LM findings. Clinical data at the time of renal biopsy and during a mean follow-up of 46 months were extracted from the records of 69 SLE patients with proliferative LN (WHO class III/IV). Biopsy specimens were analyzed by LM for AI and CI, while IFM was performed on cryostat sections with the use of antisera against IgG, IgM, IgA, C3, C1q and fibrin. IFM findings were recorded in terms of the localization (glomerular, tubular or vascular) and intensity of fluorescence (score from zero to three). IFM findings were then related to clinical and LM findings and its prognostic value studied by survival analysis. Glomerular immune deposits were present in 99% of patients, tubular deposits in 38% and vascular deposits in 17%. A 'full-house' pattern (all three Ig classes) was found in 67% of biopsies and C3 and C1q deposits in 93% and 74% respectively. Median scores for AI and CI were 6 (1-18) and 3 (0-10); aside from a negative correlation between IgA deposits and CI, we found no other correlation between the amount or type of immune deposits and AI or CI. IgM deposits were associated with high serum levels of anti-dsDNA, while IgG deposits correlated with high ESR and serum creatinin levels. IFM scores were not related to steroid dose at the time of biopsy and neither type of glomerular, tubular or overall renal immune deposits had prognostic value for renal survival. Renal immunofluorescence does not reflect light microscopy findings in patients with PLN and does not contribute prognostic information in patients with PLN. Lupus (2000) 9, 504-510.     

Correlation between hemoglobin and progression of renal function in patients with proliferative lupus nephritis

<正>Objective To explore the correlation between hemoglobin( Hb) and progression of renal function in patients with proliferative lupus nephritis( PLN).Methods Data of biopsy-proven PLN patients from January 2010 to February 2019 in Department of Nephrology,     

循环中内皮细胞损伤生物标志物在判断狼疮性肾炎肾脏血管病变中的应用

目的：观察狼疮性肾炎（LN）患者血液中血栓调节蛋白（TM）、血管内皮细胞粘附分子1（VCAM-1）和E选择素（E-selectin）表达情况,探讨内皮损伤生物标记物与肾脏血管病变的关系.方法：30例经肾活检证实为LN伴血管病变患者、30例LN不伴血管病变患者和25名健康志愿者,ELISA法检测血循环中可溶性TM、VCAM-1和E-selectin水平.结果：不伴血管病变组LN患者TM和VCAM-1水平与正常对照组无明显差别,伴血管病变组患者TM和VCAM-1水平均显著高于不伴血管病变组和正常对照组（P＜0.01）.伴血管病变患者的E-selectin水平与正常对照组无明显差异.伴血管病变组患者TM与肌酐水平呈正相关（r=0.625,P＜0.01）.在伴血管病变LN患者中,合并血栓性微血管病变（TMA）患者TM水平明显高于不伴有TMA患者（P＜0.01）.结论：结合肾组织病理检查,检测循环中的TM和VCAM-1对评估LN患者肾脏血管病变具有重要的临床意义.     

Illness perceptions in patients with systemic lupus erythematosus and proliferative lupus nephritis

This study investigated the illness perceptions of patients with systemic lupus erythematosus (SLE) and whether perceptions are influenced by type of treatment for proliferative lupus nephritis. In addition, the illness perceptions of SLE patients were compared with those of patients with other chronic illnesses. Thirty-two patients who had experienced at least one episode of proliferative lupus nephritis were included. Patients were treated with either a high or low-dose cyclophosphamide (CYC) regimen (National Institutes of Health [NIH] vs. Euro-Lupus protocol). Illness perceptions were measured with the Brief Illness Perception Questionnaire (B-IPQ) and a drawing assignment. The low-dose CYC group perceived their treatment as more helpful than the high-dose CYC group. In comparison with patients with asthma, SLE patients showed more negative illness perceptions on five of the eight illness perception domains. Drawings of the kidney provided additional information about perceptions of treatment effectiveness, kidney function and patients' understanding of their illness. Drawing characteristics showed associations with perceptions of consequences, identity, concern and personal control. These findings suggest that the type of treatment SLE patients with proliferative lupus nephritis receive may influence perceptions of treatment effectiveness. In addition, patients' drawings reveal perceptions of damage caused by lupus nephritis to the kidneys and the extent of relief provided by treatment. The finding that SLE is experienced as a more severe illness than other chronic illnesses supports the need to more frequently assess and aim to improve psychological functioning in SLE patients.     

Evaluation of renal vascular lesions using circulating endothelial cells in patients with lupus nephritis

Objective. Currently the detection of renal vascular lesions(VLS) mainly depends on biopsy examination, and lacks surrogatebiomarkers for clinical dynamic evaluation. The aim of thisstudy is to find the correlation between numbers of circulatingendothelial cells (CECs) and renal VLS in lupus nephritis (LN). Methods. Thirty LN patients with VLS and 30 LN patients withoutVLS were recruited. Thirty age- and sex-matched healthy volunteersserved as controls. CECs were isolated from peripheral bloodwith anti-CD-146-coated immunomagnetic Dynabeads and were countedunder microscopy. Parameters of renal involvement, includingblood urea nitrogen, serum creatinine, 24 h urine protein excretionand quantitative urine sedimentation were also measured. Results. The number of CECs showed no difference between LNpatients without VLS and controls. In patients with VLS, thenumber of CECs was significantly higher than those without VLS(P < 0.01). A strong positive correlation was found betweenCECs and serum creatinine (r = 0.503, P < 0.01) and meanblood pressure (r = 0.423, P < 0.05). In all LN patientswith VLS, CEC number of the patients with thrombotic microangiopathy(TMA) significantly increased compared with those without TMA(P < 0.01). Conclusion. Numeration of CECs may serve as a potential anduseful marker for vasculopathy in LN. Dynamic observations ofCEC number can be used not only to provide evidence for monitoringdisease severity and disease activity, but also to determinetherapy efficacy in LN patients. KEY WORDS: Lupus nephritis, Renal vascular lesion, Circulating endothelial cells Submitted 17 July 2007; revised version accepted 18 December 2007.     

尿微量蛋白测定与肝硬化肾实质损害

了解常规尿检阴性肝硬化患者的肾实质损害。采用放免法，对54例肝硬化患者和22例正常人的尿白蛋白、转铁蛋白、β2－球蛋白、视网膜结合蛋白、N－乙酰－β－D氨基葡萄糖苷酶进行了测定，采用双核素肾图技术测定了28例肝硬化患者有效肾血浆流量。所测尿微量蛋白在肝硬化组显著高于正常对照组，肝功能ChildA、B、C级各组中浓度依次升高，ERPF下降组（＜450ml/min）显著高于ERPF正常组（＞40ml/min）。肝硬化患者存在常规尿检不能发现的肾小球和肾小管损害，肝肾功能越差损害越严重，尿微量蛋白测定有助于早期发现。