生物制剂在狼疮肾炎治疗中的应用

<正>一、狼疮肾炎治疗的演变和局限系统性红斑狼疮(systemic lupus erythematosus,SLE)是自身免疫介导的,以免疫性炎症为突出表现的弥漫性结缔组织病。血清抗核抗体为代表的多种自身抗体阳性和多系统受累是SLE的主要临床特征。狼疮肾炎(lupus nephritis,LN)是SLE临床最常见的严重并发症。诊断SLE时50%伴有肾脏损害,而在SLE整体病程中超过60%的成人和超     

中西医结合治疗狼疮肾炎的Meta-分析

狼疮肾炎（1upus nephritis，LN）是影响系统性红斑狼疮（SLE）预后的重要脏器合并症之一，是SLE的一种常见且严重的肾脏损害，约5％～25％的SLE患者是以LN为首发临床表现^[1]。近年来，有关中西医结合治疗狼疮肾炎报道逐渐增多，笔者采用Meta分析方法对中西医结合治疗狼疮肾炎的疗效进行系统评价。     

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。     

狼疮肾炎中西医结合治疗

正系统性红斑狼疮(SLE)是全身自身免疫性疾病。全球成人SLE患病率为30～150/100 000例,死亡风险高于普通人群2～5倍[1,2]。狼疮肾炎(LN)是SLE最常见的严重靶器官损伤,受累患者超过60%[2,3]。以糖皮质激素联合免疫抑制剂为主体的标准治疗方案的应用使SLE预后大为改观,10年生存率达91%[4]。然而LN治疗12个月仍有一半患者不能获得完全缓解,高达50%患者治疗缓解后出现复发,超过10%患者发展为终末期肾病[2,3]。     

以严重低蛋白血症和少量蛋白尿为主要临床表现的狼疮肾炎临床及病理分析

我们报道一组以大量胸腹水、严重低蛋白血症伴少量蛋白尿为临床特征的狼疮肾炎（LN）患者，分析此类患者的临床病理特点、诊断思路及治疗转归，以加深临床医师对LN并发由系统性红斑狼疮（SLE）导致的失蛋白性肠病（PLE）诊治的认识。     

狼疮性肾炎持续性蛋白尿影响因素研究进展

<正>系统性红斑狼疮(SLE)是一种表现为多系统损害的慢性自身免疫性疾病。狼疮性肾炎(LN)是SLE最为常见和严重的临床表现,是继发性肾脏疾病中导致终末期肾衰竭的常见病因。有结果显示将近60%SLE患者在疾病发展过程中将发展为临床相关肾炎。LN的诊断标准为在确诊SLE的基础上,有肾损害的表现,如持续性蛋白尿(0.5 g/d)或管型(可为红细胞,血红蛋白,颗粒、管状或混合型),其诊断金标准为肾穿刺活     

狼疮肾炎治疗的前景

狼疮肾炎(LN)是我国最常见的也是最重要的继发性肾小球疾病。自从半个多世纪以前人们开始应用皮质激素治疗系统性红斑狼疮以来,激素治疗已成为狼疮肾炎治疗的主流。然而,重症狼疮肾炎(主要是Ⅳ型及部分Ⅲ型)的高死亡率并未因此得到解决。上个世纪80年代美国国立卫生研究院(NIH)倡导的环磷酰胺(CTX)大剂量静脉注射疗法也曾被寄予厚望,但直到20世纪结束,Ⅳ型LN的5年肾存活率始终未能超过85%,人们普遍认识到激素及免疫抑制剂的副作用已构成重症狼疮肾炎治疗的主要问题。不少学者明确指出,50%的重症狼疮肾炎患者是死于治疗中的严重合并症(特…     

老年系统性红斑狼疮临床特点分析

目的：探讨老年系统性红斑狼疮（systemic lupus erythematosus,SLE）39例患者的临床表现、实验室检查及肾脏损害情况,与同期确诊的青年SLE40例患者的上述指标进行对比。方法：观察两组患者临床特点、血常规、自身抗体、蛋白尿、肾功能、活动指数（SLEDAI Score）、肾脏病理改变及治疗后感染情况。结果：老年组狼疮SLEDAI评分明显低于青年组,皮疹、狼疮脑病发生率和狼疮特异性抗体（抗ds-DNA）的阳性率显著低于青年组（P〈0.05）,但发热、关节炎高于青年组（P〈0.05）,肾脏是老年SLE的最常见累及脏器,且重型狼疮性肾炎（LN）（Ⅳ、Ⅴ型）的发病率与青年组发病的SLE无差别。老年组治疗1个月内继发感染率显著高于青年组（P〈0.05）。结论：老年SLE与青年SLE临床特征有许多不同之处,且起病隐匿,易误诊,治疗时并发症高于青年人,须谨慎用药。     

狼疮性肾炎治疗的新进展

系统性红斑狼疮（systemic lupus erythematosus,SLE）是一种以多系统受累和血清中出现自身抗体为特征的自身免疫性疾病。60％～80％的SLE患者可有肾脏受累,表现为蛋白尿、血尿,或伴肾衰竭,即狼疮性肾炎（lupus nephritis,LN）。LN是我国最常见的继发性肾炎,有多种临床和病理类型,治疗必须遵循个体化原则,现就LN治疗的新进展作一综述。     

狼疮肾炎的诊断和治疗

系统性红斑狼疮(SLE)是自身免疫介导的,以免疫性炎症为突出表现的弥漫性结缔组织病.血清中出现以抗核抗体为代表的多种自身抗体和多系统受累是SLE的两个主要临床特征.狼疮肾炎(LN)是SLE最常见和最严重的内脏损害,是决定SLE预后的最重要因素.     

Membranous Lupus Nephritis in a Renal Allograft: Response to Mycophenolate Mofetil Therapy

Membranous lupus nephritis in a renal allograft is considered rare. A 43-year-old man with quiescent systemic lupus erythematosus (SLE) received a HLA identical transplant from his sister and 4 years later developed persistent nephrotic range proteinuria and morphological features most compatible with membranous lupus nephritis on biopsy. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists, although successful in reducing proteinuria, were associated on three occasions with acute allograft dysfunction. Sustained reduction of proteinuria and stable graft function were achieved using mycophenolate mofetil (MMF). MMF is emerging as a new therapy for primary renal disease in SLE. This is the first report of successful treatment of membranous lupus nephritis in an allograft using MMF. We review all cases of transplant-associated membranous lupus nephritis in the English literature.     

Anti-pentraxin 3 auto-antibodies might be protective in lupus nephritis: a large cohort study

Objectives: Anti-pentraxin 3 (PTX3) auto-antibodies were found to be associated with the absence of renal involvement in systemic lupus erythematosus (SLE). This study is to investigate the prevalence of anti-PTX3 auto-antibodies and their clinical significance based on a large Chinese lupus nephritis cohort.

Methods: One hundred and ninety-six active lupus nephritis patients, 150 SLE patients without clinical renal involvement, and 100 healthy controls were enrolled. Serum anti-PTX3 auto-antibodies and PTX3 levels were screened by enzyme-linked immunosorbent assay (ELISA). The associations between anti-PTX3 auto-antibodies and clinicopathological parameters in lupus nephritis were further analyzed.

Results: Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement (19.4% (38/196) versus 40.7% (61/150), p?r?=??.143, p?=?.047). The levels of proteinuria, serum creatinine, and the prevalence of thrombotic microangiopathy were significantly higher in patients with higher PTX3 levels (≥3.207?ng/ml) and without anti-PTX3 auto-antibodies compared with patients with lower PTX3 levels (<3.207?ng/ml) and with anti-PTX3 auto-antibodies (4.79 (3.39–8.28) versus 3.95 (1.78–7.0), p?=?.03; 168.84?±?153.63 versus 101.44?±?47.36, p?=?.01; 34.1% (14/41) versus 0% (0/9), p?=?.04; respectively).

Conclusion: Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement and associated with less severe renal damage, especially with the combined evaluation of serum PTX3 levels.     

Proliferation signal inhibitors in the treatment of lupus nephritis: Preliminary experience

Aim: Proliferation signal inhibitors (PSI) have demonstrated efficacy in prevention and treatment in an animal model of lupus nephritis (LN) but there are no data regarding the use of PSI in human LN. We report here our experience of using PSI treatment in seven patients with severe proliferative lupus nephritis. Methods: This is a retrospective study on patients with proliferative lupus nephritis who had received PSI treatment. Results: Seven patients were included. Two patients had concomitant membranous lupus nephropathy. The indications for PSI included mycophenolate mofetil intolerance (n = 4), history of malignancy (n = 2) and leucopoenia (n = 1). Five patients were given PSI when disease was active. Two had treatment discontinued because of acute cholecystitis and leucopoenia, respectively. In the other three patients combined steroid and PSI treatment as induction therapy led to improvements in serology, renal function and proteinuria. In two patients treated with PSI and low‐dose steroid as maintenance immunosuppression, both maintained stable lupus serology, renal function and proteinuria over 18 months. Side‐effects included dyslipidemia and oral ulcers. Conclusion: Proliferation signal inhibitors warrants further investigation as an alternative immunosuppressive treatment in lupus nephritis.     

Lupus nephritis: a clinical review for practicing nephrologists

The renal manifestations in systemic lupus erythematosus (SLE) are protean and difficult to categorize into clinical syndromes and histologic classes. Lupus nephritis is frequently unrecognized until full-blown nephritic and/or nephrotic syndrome with renal failure emerge. Epidemiologically, approximately one third of SLE patients from unselected populations have renal involvement early during the disease. Most renal abnormalities emerge within the first few years of SLE diagnosis. Currently, most nephrologists agree that an early renal biopsy is worthwhile in those SLE patients with abnormal urinalysis and/or reduced renal function. First, it provides a histologic categorization of the glomerulonephritis as well as an assessment of the degree of activity and chronicity. Second, it provides vital prognostic information. Third, it is beneficial in planning a more rational therapy with or without potentially toxic immunosuppressive agents. Over the last 3 decades, many controlled clinical trials for treatment of lupus nephritis have been completed with a few therapeutic immunosuppressive regimens. Among those agents used. cyclophosphamide and azathioprine provide a reduction of morbidity in those patients afflicted with proliferative forms of lupus glomerulonephritis. A new immunosuppressive agent, mycophenolate mofetil, is being studied for treatment of proliferative forms of lupus glomerulonephritis in a controlled clinical trial at our institution. Immunosuppressive agents and the availability of dialysis and transplantation have improved the survival of patients with lupus nephritis, in particular those with proliferative forms.     

Systemic lupus erythematosus: A follow-up study of Japanese patients with end-stage renal failure treated with haemodialysis

Summary: In order to explore the clinical course of Japanese patients with systemic lupus erythematosus (SLE) in end-stage renal failure, the clinical findings from 26 patients who had received haemodialysis were analysed. Each patient was followed for 72 months from the onset of clinical lupus nephritis to the initiation of haemodialysis. In most patients, renal disease progressed to end-stage renal failure despite clinical quiescence of SLE, which remained inactive throughout haemodialysis treatment. Seven patients (27%) had clinically active SLE with high dose prednisolone (mean; 49.3 mg per day) at initiation of haemodialysis. These patients had relatively rapid progression of their renal failure and 2 patients died within 1 month of their first haemodialysis. During the follow-up period from starting haemodialysis for an average of 44 months, most patients received ongoing haemodialysis while their SLE remained clinically inactive. Six patients (23%) died, 5 of those within 1 month from starting hemodialysis. the results of this long-term follow up of a large number of haemodialysis patients with lupus nephritis indicate that: (i) most patients with lupus nephritis undergoing haemodialysis have an excellent survival rate; and (ii) patients with active SLE at initiation of haemodialysis have a high mortality rate (within 1 month). We therefore conclude that more effective treatment for SLE in the presence of renal failure is required for these patients.     

Nephrotic syndrome associated with focal segmental glomerulosclerosis in a patient with systemic lupus erythematosus and membranous glomerulonephritis in remission

Renal involvement is frequent in systemic lupus erythematosus (SLE). This lesion, termed lupus nephritis, has been reported clinically in at least 50% of the patients. It is generally assumed that in patients with SLE, renal abnormalities detected clinically are caused by lupus nephritis, especially lupus glomerulonephritis (GN). Thus, renal biopsy is performed not for diagnostic purposes, but rather for determining the type and extent of renal involvement. However, clinically significant renal abnormalities unrelated to lupus nephritis have rarely been described in patients with SLE. The reported case serves to emphasize this consideration. The patient was a 41-year-old woman who presented 11 years previously with severe hypertension, nephrotic syndrome, and a serum creatinine level of 2.9 mg/dL. Renal biopsy showed membranous GN and ischemic damage. After a prolonged remission induced by steroids and cyclophosphamide, the patient presented with nephrotic syndrome and a serum creatinine level of 2.1 mg/dL. Although she was normotensive at that time, there were features of SLE. Repeated renal biopsy showed focal segmental glomerulosclerosis without the changes of membranous GN or any type lupus GN. This case illustrates two interesting observations, ie, resolution of membranous GN and nonlupus renal lesions in patients with SLE.     

系统性红斑狼疮并发继发性抗磷脂综合征肾损害11例临床病理分析

目的 分析系统性红斑狼疮（SLE）并发继发性抗磷脂综合征（APS）肾损害的临床病理表现,旨在提高对该类疾病的认识。 方法 回顾性分析北京协和医院2000年至2010年期间确诊SLE并发继发性APS（SLE伴APS）并行肾组织学检查的11例患者的资料,分析其临床病理特点,并比较其和SLE不伴APS患者在肾损害的临床病理及预后上的差异。 结果 11例SLE伴APS患者均有肾脏受累,突出表现为高血压（54.5%）、大量蛋白尿（≥3.5 g/d）（72.7%）和肾功能异常（45.5%）。SLE伴APS患者的舒张压、平均动脉压以及肾小球滤过率（eGFR）均明显高于SLE不伴APS患者（均P < 0.05）。8例（72.7%）SLE伴APS患者存在肾内血管的“血管闭塞性表现”,即符合抗磷脂综合征肾病（APSN）的病理表现,包括肾小血管、肾小球毛细血管血栓形成以及肾小动脉内膜增生、局灶性肾皮质萎缩、肾小管甲状腺样化,其中慢性APSN表现5例（45.5%）,急性APSN表现4例（36.4%）（其中1例同时有急性和慢性表现）;其APSN的发生率以及急性APSN的发生率明显高于SLE不伴APS患者（P < 0.05）。 结论 SLE并发APS肾损害患者除狼疮肾炎外,多并发APSN,临床上高血压和肾功能异常更为突出。     

Recurrence of SLE in transplanted kidneys: a follow-up transplant biopsy study.

Renal transplant biopsies were obtained from 16 patients with systemic lupus erythematosus 6 months to 11 years post-transplant. Eight biopsies were taken on clinical grounds while eight were elective. Histopathological findings suggesting recurrent lupus nephritis were found in seven biopsies, five of which were taken on clinical indication. By light-microscopy, five graft biopsies showed proliferative glomerulopathy and two glomerulosclerosis. Immunofluorescence was positive for IgM and C3 in a finely granular pattern in all biopsies, for C1q in three, but for IgG in only two. Electron-dense deposits were found in all seven biopsies with predominantly subendothelial location. All but one patient had clinical signs of renal involvement, but only three had extrarenal symptoms and three had serological signs of active SLE. Upon increased immunosuppressive therapy, renal and serological signs improved but one graft was later lost due to recurrent SLE nephritis.     

Lupus nephritis in Chinese children — a territory-wide cohort study in Hong Kong

We report a multicenter study of Chinese children in Hong Kong with systemic lupus erythematosus (SLE) nephritis. Children were included if: they fulfilled the ACR criteria, had significant proteinuria or casturia, were Chinese and younger than 19 years and had been diagnosed with SLE between January 1990 and December 2003. Investigators in each center retrieved data on clinical features, biopsy reports, treatment and outcome of these patients. There were 128 patients (eight boys, 120 girls; mean age: 11.9±2.8 years). About 50% presented with multisystem illness and 40% with nephritic/nephrotic symptoms. Negative anti-dsDNA antibodies were found in 6% of the patients. Renal biopsy revealed WHO Class II, III, IV and V nephritis in 13 (10%), 22 (17%), 69 (54%) and 13 (10%) patients, respectively. The clinical severity of the nephritis did not accurately predict renal biopsy findings. The follow-up period ranged from 1 to 16.5 years (mean±SD: 5.76±3.61 years). During the study five patients died (two from lupus flare, one from cardiomyopathy, two from infections). Four patients had endstage renal failure (ESRF) (one died during a lupus flare). All deaths and end-stage renal failure occurred in the Class IV nephritis group. Chronic organ damage was infrequent in the survivors. The actuarial patient survival rates at 5, 10 and 15 years of age were 95.3, 91.8, and 91.8%, respectively. For Class IV nephritis patients, the survival rates without ESRF at 5, 10, and 15 years were 91.5, 82.3 and 76%, respectively. The survival and chronic morbidity rates of the Chinese SLE children in the present study are comparable to those of other published studies.An erratum to this article can be found at