Changes in macrophage infiltration and podocyte injury in lupus nephritis patients with repeated renal biopsy: Report of three cases

BACKGROUND In this study,we retrospectively analysed macrophage infiltration and podocyte injury in three patients with diffuse proliferative lupus nephritis(LN)who un-derwent repeated renal biopsy.CASE SUMMARY Clinical data of three diffuse proliferative LN patients with different pathological characteristics(case 1 was LN IV-G(A),case 2 was LN IV-G(A)+V,and case 3 was LN IV-G(A)+thrombotic microangiopathy)were reviewed.All patients underwent repeated renal biopsies 6 mo later,and renal biopsy specimens were studied.Macrophage infiltration was assessed by CD68 expression detected by immunohistochemical staining,and an immunofluorescence assay was used to detect podocin expression to assess podocyte damage.After treatment,Case 1 changed to LN III-(A),Case 2 remained as type V LN lesions,and Case 3,which changed to LN IV-S(A),had the worst prognosis.We observed reduced macro-phage infiltration after therapy.However,two of the patients with active lesions after treatment still showed macrophage infiltration in the renal interstitium.Before treatment,the three patients showed discontinuous expression of podocin.Notably,the integrity of podocin was restored after treatment in Case 1.CONCLUSION It may be possible to reverse podocyte damage and decrease the infiltrating ma-crophages in LN patients through effective treatment.

Focus on laboratory tests related to the pathological types of lupus nephritis to implement renal biopsy as early as possible:clinical and pathological analysis of 217 cases of single center lupus nephritis

Objective:To analyze the clinical and laboratory indices of patients with lupus nephritis(LN)of different pathological types and explore the related factors of LN pathological classification,it is helpful to grasp the timing of renal biopsy.Methods:The clinical manifestations,laboratory parameters and renal pathological types of LN patients in recent 20 years were analyzed retrospectively by SPSS 26.0 software.Results:In this study,the first three pathological types were V,IV,V+IV;latent nephritis was common in type II and V;nephritic syndrome was common in type V;nephrotic syndrome was common in type V+IV;chronic renal insufficiency group was mostly type IV;pathological types were correlated with serum creatinine,C3,albumin and erythrocyte sedimentation rate(r=0.315,P<0.001),and serum creatinine was moderately correlated(r=0.315,P<0.001);AI,CI and SLEDAI scores were significantly different among LN patients of different pathological types.Conclusion:LN is closely related to clinical pathology,clinical manifestations,comprehensive analysis of laboratory indicators and SLEDAI score to make a preliminary prediction of LN pathological type,help to initially assess the severity of pathology,improve the timing of renal biopsy implementation,optimize the timing of treatment.

Association of C-reactive protein and complement factor H gene polymorphisms with risk of lupus nephritis in Chinese population

BACKGROUND Complement overactivation is a major driver of lupus nephritis(LN).Impaired interactions of C-reactive protein(CRP)with complement factor H(CFH)have been shown as a pathogenic mechanism that contributes to the overactivation of complement in LN.However,genetic variations of neither CRP nor CFH show consistent influences on the risk of LN.AIM To examine whether genetic variations of CRP and CFH in combination can improve the risk stratification in Chinese population.METHODS We genotyped six CRP single nucleotide polymorphisms(SNPs)(rs1205,rs3093062,rs2794521,rs1800947,rs3093077,and rs1130864)and three CFH SNPs(rs482934,rs1061170,and rs1061147)in 270 LN patients and 303 healthy subjects.RESULTS No linkage was found among CRP and CFH SNPs,indicating lack of genetic interactions between the two genes.Moreover,CRP and CFH SNPs,neither individually nor in combination,are associated with the risk or clinical manifestations of LN.Given the unambiguous pathogenic roles of the two genes.CONCLUSION These findings suggest that the biological effects of most genetic variations of CRP and CFH on their expressions or activities are not sufficient to influence the disease course of LN.

LncRNA-NEAT1调控miR-182-5p表达对狼疮性肾炎肾系膜细胞损伤的影响

目的探讨长链非编码RNA(LncRNA)核旁丛组装转录本1(NEAT1)在狼疮性肾炎(lupus nephritis,LN)中通过微小RNA(miR)-182-5p/叉头盒蛋白O1(FoxO1)/β-连环蛋白(β-catenin)轴对肾系膜细胞损伤的影响。方法收集2019年3月至2021年7月凉山州第二人民医院收治的32例LN患者(LN组)外周血和32例体检健康者(健康对照组)外周血,实时荧光定量聚合酶链反应(qRT-PCR)法检测外周血单个核细胞中NEAT1以及miR-182-5p、FoxO1、β-catenin mRNA表达水平,酶联免疫吸附(ELISA)法检测血清炎症因子肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6和IL-1β含量。采用20%LN患者血清处理肾系膜细胞的方法构建LN肾系膜细胞模型,造模完成后将细胞分为对照组(正常培养,不转染)、模型组(加入5μg/mL脂多糖培养)、si-NC组(转染si-NC后加入5μg/mL脂多糖培养)、si-NEAT1组(转染si-NEAT1后加入5μg/mL脂多糖培养)、si-NEAT1+anti-miR-NC组(共转染si-NEAT1和anti-miR-NC后加入5μg/mL脂多糖培养)、si-NEAT1+anti-miR-182-5p组(共转染si-NEAT1和anti-miR-182-5p后加入5μg/mL脂多糖培养)。qRT-PCR法检测各组细胞NEAT1、miR-182-5p表达水平;ELISA法测定各组细胞炎症因子水平;乳酸脱氢酶(LDH)试剂盒检测各组细胞LDH含量;细胞计数试剂盒8(CCK-8)实验检测各组细胞增殖活力;流式细胞仪分析各组细胞凋亡情况;免疫印迹法检测各组细胞FoxO1、β-catenin蛋白表达水平。结果与健康对照组比较,LN组患者外周血单个核细胞中NEAT1、FoxO1、β-catenin mRNA表达水平以及血清中炎症因子TNF-α、IL-6、IL-1β含量均显著上升,miR-182-5p表达水平显著下降(P<0.05)。与对照组比较,模型组肾系膜细胞增殖活力、FoxO1和β-catenin蛋白水平以及LDH、TNF-α、IL-6和IL-1β水平均明显增加,miR-182-5p表达水平明显降低(P<0.05)。敲低NEAT1后,细胞增殖活力和炎症反应减弱,FoxO1和β-catenin蛋白表达明显下调(P<0.05);抑制miR-182-5p表达可减轻NEAT1敲低对LN肾系膜细胞模型细胞增殖、炎症因子及FoxO1、β-catenin蛋白表达的影响(P<0.05)。各组细胞间凋亡率无显著变化(P>0.05)。结论敲低NEAT1可通过靶向负调控miR-182-5p表达,抑制LN肾系膜细胞过度增殖,降低炎症反应,其可能与抑制FoxO1/β-catenin通路有关。

Network pharmacology and data analysis method to explore the traditional Chinese medicine regulates ferroptosis key genes in the occurrence and prognosis of lupus nephritis

Purpose:To explore the traditional Chinese medicine(TCM)regulates ferroptosis key genes in the occurrence and development of lupus nephritis(LN)based on biological information database.Patients and methods:Ferroptosis related genes were identified based on FerrDb database and literature retrieval.Used the OMIM,Gene Cards,Drug Bank to obtain the targets of LN.Cytoscapes 3.8.2 software and STRING database were used to analyze protein-protein interaction(PPI)network.Metacape software and Weishengxin were used to analyze the gene ontology(GO)classification and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.UniProt Database and Traditional Chinese Systems Pharmacology Database and Analysis Platform analysis platform were used to obtain the data table of key TCM and related targets.Cytoscapes 3.8.2 software was used to analyze the PPI network.Results:A total of 401 ferroptosis-related genes,361 LN related genes and 21“Ferroptosis-LN”intersection genes were obtained.Ferroptosis in the occurrence and prognosis of LN mainly involved the inflammatory response,cell activation,positive regulation of chemokine production and it was mainly involved in necroptosis,inflammatory bowel disease,ferroptosis and other pathways.A total of 412 TCMs containing key genes of“Ferroptosis-LN”were acquired.The most key genes were contained in Mahuang,Gehua,Baiguo,Chuanniuxi,Jinyinhua.15 key genes of“TCM-LN”were obtained.5 ferroptosis-related key genes in LN regulated by TCM were obtained,which were IL1β,TLR4,IFNG,STAT3 and HMOX1.Conclusion:TCM,such as Mahuang,Gehua,Baiguo,Chuanniuxi,Jinyinhua,may affect the occurrence and development of LN through the key ferroptosis genes,such as IL1B,TLR4,IFNG,STAT3 and HMOX1.

LncRNAHOTAIR靶向miR-17-5p/TXNIP对狼疮性肾炎进展的机制研究

目的探讨长链非编码RNA同源盒基因转录反义RNA(LncRNAHOTAIR)靶向miR-17-5p/硫氧还蛋白相互作用蛋白(TXNIP)对狼疮性肾炎(LN)进展的机制。方法取60只MRL/lpr雌性小鼠,随机分为模型组、LncRNAHOTAIR敲低组、miR-17-5p agomir组、阴性对照组和LncRNAHOTAIR敲低+miR-17-5p antagomir组,每组12只,另取12只C57BL/6J雌性小鼠作为对照组,检测各组小鼠肾功能、免疫器官指数;以HE染色实验检测各组小鼠肾组织病理形态;以酶联免疫吸附测定(ELASA)法测定各组小鼠血清抗双链DNA(dsDNA)、免疫细胞因子免疫球蛋白G(IgG)、白细胞介素-6(IL-6)、单核细胞趋化蛋白1(MCP-1)及肿瘤坏死因子-α(TNF-α)水平;以实时荧光定量多聚核苷酸链式反应(qPCR)和免疫印迹法检测各组小鼠肾组织LncRNAHOTAIR、miR-17-5p及TXNIP表达。以双荧光素酶报告基因实验检测小鼠肾小球系膜细胞中LncRNAHOTAIR对miR-17-5p、miR-17-5p对TXNIP的靶向调节。结果与对照组比较,模型组小鼠肾组织发生严重病理损伤,胸腺指数、脾脏指数、miR-17-5p表达降低(P<0.05),尿蛋白浓度、血尿素氮(BUN)、血清抗dsDNA及IgG、IL-6、MCP-1、TNF-α、肾组织LncRNAHOTAIR及TXNIP表达升高(P<0.05)。与模型组比较,Ln⁃cRNAHOTAIR敲低组、miR-17-5p agomir组小鼠肾组织病理损伤减轻,胸腺指数、脾脏指数、miR-17-5p表达升高(P<0.05),尿蛋白浓度、BUN、血清抗dsDNA及IgG、IL-6、MCP-1、TNF-α、肾组织LncRNAHOTAIR及TXNIP表达降低(P<0.05)。下调miR-17-5p可减弱敲低LncRNAHOTAIR组对模型组小鼠各指标的作用。结论敲低LncRNAHOTAIR可通过上调miR-17-5p而降低TXNIP表达,进而减少LN小鼠免疫炎性因子产生,增强其免疫功能,抑制体内炎症发生发展,最终减轻小鼠肾组织损伤并改善其肾功能。

Advances in Diagnosis and Treatment of Lupus Nephritis(Class V)

Membranous lupus nephritis(MLN),class V,is a distinct LN characterized by immune complex deposition on subepithelial kidney biopsy.MLN is often associated with nephrotic syndrome.The histology of MLN is very similar to idiopathic(primary)membranous nephropathy(pMN).However,MLN usually has abundant mesa-glomerular deposits absent in primary membranous nephropathy.The clinical manifestations,management,and prognosis of MLN differ from other types of LN(type III,IV,or mixed type III/IV+V).Although immunosuppressive therapy is often necessary for MLN,the optimal treatment regimen is yet to be determined.This review summarizes the progress in the diagnosis and treatment of MLN and discusses the selection of immunosuppressants for MLN.

Effect of Rituximab Versus Mycophenolate Mofetil or Cyclophosphamide as Control in Lupus Nephritis:A Meta-Analysis

Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7 studies involving 645 participants with lupus nephritis at the commencement of the investigation;198 of them were treated with rituximab,while 447 were treated with mycophenolate mofetil or cyclophosphamide.We determined the odds ratio(OR)and mean difference(MD)with 95%confidence index(CI)to compare rituximab’s efficacy to that of mycophenolate mofetil or cyclophosphamide as control in lupus nephritis using random-or fixed-effects model by dichotomous or continuous techniques.Results:The rituximab group showed significantly higher complete renal remission rate(OR=2.52;95%CI 1.30-4.91,P=0.006)and total renal remission rates(OR=2.22;95%CI 1.36-3.63,P=0.001)than the control group.However,there was no significant difference in terms of end Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score(MD-1.16;95%CI-2.88-0.57,P=0.19),proteinuria(MD-0.31;95%CI-0.70-0.09,P=0.013),and serum creatinine(MD 0.01;95%CI-0.04-0.07,P=0.64)between the rituximab group and the control.Conclusion:Rituximab exhibited significantly greater complete renal remission rate and total renal remission rates,with no significant difference in terms of shorter-end SLEDAI,proteinuria,and serum creatinine,compared with the control in individuals with lupus nephritis.

狼疮肾炎患者血清lncRNA TUG1、miR-144的表达及其意义

目的分析血清长链非编码核糖核酸牛磺酸上调基因1(lncRNA TUG1)、微小核糖核酸-144(miR-144)表达与狼疮肾炎(LN)患者预后的关系。方法选取2020年1月—2021年6月遂宁市中心医院风湿免疫科收治的LN患者104例为LN组,根据随访期间是否发生终末期肾病(ESRD)分为预后不良亚组36例和预后良好亚组68例,另选取同期体检健康者40例为健康对照组。采用实时荧光定量聚合酶链式反应试剂盒检测血清lncRNA TUG1、miR-144表达。经TargetScan网站预测lncRNA TUG1与miR-144的结合位点,采用Pearson相关性分析LN患者血清lncRNA TUG1与miR-144表达的相关性。多因素Logistic回归分析LN患者预后不良的危险因素,受试者工作特征(ROC)曲线分析血清lncRNA TUG1、miR-144表达对LN患者预后不良的预测价值。结果与健康对照组比较,LN组血清lncRNA TUG1表达降低,miR-144表达升高(t/P=15.885/<0.001、15.808/<0.001)。经TargetScan网站预测,lncRNA TUG1与miR-144存在结合位点;Pearson相关性分析显示,LN患者血清lncRNA TUG1与miR-144表达呈负相关(r=-0.797,P<0.001)。随访2年,104例LN患者ESRD发生率为34.62%(36/104)。多因素Logistic回归分析显示,慢性肾脏病分期4期和miR-144升高为LN患者肾脏预后不良的独立危险因素[OR(95%CI)=1.197(1.062~1.349)、1.108(1.047~1.172)],诱导治疗后完全缓解和估算肾小球滤过率、lncRNA TUG1升高为独立保护因素[OR(95%CI)=0.305(0.101~0.923)、0.979(0.960~0.998)、0.841(0.750~0.943)];ROC曲线分析显示,血清lncRNA TUG1、miR-144表达及二项联合预测LN患者肾脏预后不良的曲线下面积(AUC)分别为0.772、0.773、0.911,二者联合预测的AUC最大(Z/P=3.239/0.001、3.247/0.001)。结论LN患者血清lncRNA TUG1低表达和miR-144高表达与肾脏预后不良有关,二者联合预测LN肾脏预后不良价值较高。

Treatment of young patients with lupus nephritis using calcineurin inhibitors

Recent advances in the management of lupus nephritis, together with earlier renal biopsy and selective use of aggressive immunosuppressive therapy, have contribut-ed to a favorable outcome in children and adolescents with systemic lupus erythematosus （SLE）. Neverthe-less, we believe that a more effective and less toxic treatment is needed to attain an optimal control of the activity of lupus nephritis. Recent published papers and our experiences regarding treatment of young patients with lupus nephritis using calcineurin inhibitors are re-viewed. Although it has been reported that intermittent monthly pulses of intravenous cyclophosphamide （IVCY） are effective for preserving renal function in adult pa-tients, CPA is a potent immunosuppressive agent thatinduces severe toxicity, including myelo- and gonadal toxicity, and increases the risk of secondary malig-nancy. Thus, treatment for controlling lupus nephritis activity, especially in children and adolescents, remains challenging. Cyclosporine A （CsA） and tacrolimus （Tac） are T-cell-specific calcineurin inhibitors that prevent the activation of helper T cells, thereby inhibiting thetranscription of the early activation genes of interleu-kin （IL）-2 and suppressing T cell-induced activation of tumor necrosis factor-α, IL-1β and IL-6. Therefore, both drugs, which we believe may be less cytotoxic, are attractive therapeutic options for young patients with lupus nephritis. Recently, a multidrug regimen of prednisolone （PDN）, Tac, and mycophenolate mofetile （MMF） has been found effective and relatively safe in adult lupus nephritis. Since the mechanisms of action of MMF and Tac are probably complementary, multidrug therapy for lupus nephritis may be useful. We propose as an alternative to IVCY, a multidrug therapy with mizoribine, which acts very similarly to MMF, and Tac, which has a different mode of action, combined with PDN for pediatric-onset lupus nephritis. We also believe that a multidrug therapy including CsA and Tac may bean attractive option for young patients with SLE and lupus nephritis

Cytomegalovirus enteritis mimicking Crohn's disease in a lupus nephritis patient:A case report

Cytomegalovirus(CMV)infection of the gastrointestinal (GI)tract has been reported in both immunocompetent and,more frequently,in immunocompromised patients.We describe a case of a 19-year-old male who developed CMV infection of the terminal ileum while receiving immunosuppression for lupus nephritis. This was a distinctly unusual site of infection which clinically mimicked Crohn's ileitis.We note that reports of terminal ileal CMV infection have been infrequent. Despite a complicated hospital course,ganciclovir therapy was effective in resolving his symptoms and normalizing his ileal mucosa.This report highlights the importance of accurate histological diagnosis and clinical follow-up of lupus patients with GI symptoms undergoing intense immunosuppression.

LUPUS NEPHRITIS COMPLICATED WITH MALIGNANT HYPERTENSION:FROM RENAL VASCULAR PATHOLOGY TO CLINICAL RELEVANCE

Objective To investigate the clinical and pathological characteristics of lupus nephritis patients complicated with malignant hypertension.Methods We retrospectively studied 19 patients with lupus nephritis complicated with malignant hypertension who underwent renal biopsy between January 2002 and December 2006.Results Of 19 patients,3 were men and 16 were women,with a mean age of 24.4±7.7 years old.All had positive antinuclear antibodies and low serum complement was found in 13 patients.All were anemic and 12 of them were thrombocytopenic.Impaired renal function was found in 17 patients with an average serum creatinine of 184.5±88.9 μmol/L.Severe intrarenal arteriolar lesion was found in all patients.Six patients had lupus vasculopathy,11 patients had renal thrombotic microangiopathy lesion,2 had severe arteriosclerosis.All patients received steroids and immunosuppressive drugs,15 received angiotensin-converting enzyme inhibitor(ACEI)/angiotensin receptor blocker(ARB)with resultant well-controlled blood pressure.Thrombocytopenia and hemolytic anemia resolved remarkably.The renal function improved or recovered in 14 of 17 patients,and 3 developed end-stage renal disease on maintenance dialysis.Conclusions Severe intrarenal vascular lesion complicated with renal nephritis parallels clinical manifestation of malignant hypertension.Renal pathology is the key of treatment strategy emphasizing on the significance of renal vascular involvement and type.On the basis of immunosuppressive drugs and steroids to control systemic lupus activity,timely initiation of ACEI/ARB could be of benefit to blood pressure control and long term renal survival.

Pediatric lupus nephritis: Management update

Childhood-onset systemic lupus erythematosus （cSLE） is a severe multisystem autoimmune disease. Renal involvement occurs in the majority of cSLE patients and is often fatal. Renal biopsy is an important investigation in the management of lupus nephritis. Treatment of renal lupus consists of an induction phase and main-tenance phase. Treatment of childhood lupus nephritis using steroids is associated with poor outcome and excess side-effects. The addition of cyclophosphamide to the treatment schedule has improved disease control. In view of treatment failure using these drugs and a tendency for non-adherence, many newer agents such as immune-modulators and monoclonal antibodies are being tried in patients with cSLE. Trials of these novel agents in the pediatric population are still lacking making a consensus in the management protocol of pediatric lupus nephritis diffcult.

Dan Bai Xiao Formula combined with glucocorticoids and cyclophosphamide for pediatric lupus nephritis:A pilot prospective study

BACKGROUND Patients with lupus nephritis(LN)typically undergo long-term treatment with glucocorticoids(GCs)and immunosuppressants.There is a growing demand for optimal therapy with better remission results and fewer side effects.Sustained traditional Chinese medicine(TCM)might be quite valuable for multitarget therapy,reducing the total dosage of GCs and minimizing the side effects of immunosuppressants.AIM To evaluate whether Dan Bai Xiao Formula(DBXF)can reduce the exposure to GCs and cyclophosphamide(CYC)and to assess the efficacy and safety of DBXF for the resolution of proteinuria and hematuria in children with LN.METHODS A 24-wk pilot study was conducted at Beijing Children’s Hospital.Children with active LN were divided into either a TCM group or a control group.Children in the TCM group received DBXF combined with GCs and CYC,and the ones in the control group received GCs and CYC every 4 wk for 24 wk.The primary endpoints of this trial were urinary protein excretion of<150 mg/d and normal serum albumin concentration and renal function.RESULTS The trial included 78 children,of whom 38 received GCs and CYC treatment(control group)and the remaining 40 received DBXF combined with GCs and CYC treatment(TCM group).At week 24,the TCM group showed a better rate of complete remission(42.5%);however,there was no significant difference compared with the control group(31.5%,P>0.05).The urine red blood cell count and urine protein level were significantly lower in the TCM group than in the control group at weeks 4,12,and 24(P<0.05).Furthermore,patients in the TCM group had a lower proportion of methylprednisolone pulses than those in the control group(1.30±1.41 vs 3.05±2.02,P<0.0001).The ending GC dose was significantly lower in the TCM group than in the control group(P<0.001).Moreover,more hepatic function damage,gastrointestinal adverse effects,and hypertension were observed in the control group than in the TCM group(P<0.05).CONCLUSION The findings suggest that DBXF treatment is effective and safe as a supplementary therapy for LN and is superior to routine GC and CYC therapy.DBXF containing combination treatment possibly results in a faster resolution of proteinuria and hematuria,smoother GC reduction,fewer methylprednisolone pulses,and fewer adverse events.

Outcome of Leflunomide in the Treatment of Proliferative Lupus Nephritis Compared to Cyclophosphamide

Background: Lupus nephritis (LN) is one of the most common presentations of Systemic lupus erythematosus (SLE). Cyclophosphamide is one of the key immunosuppressive agents for the management of LN. Leflunomide is an isoxazole immunomodulatory agent has been shown to be safe, well tolerated and effective in SLE and LN. Objective: To evaluate the outcome of leflunomide in the treatment of proliferative lupus nephritis compared to cyclophosphamide. Method: This randomized clinical trial was held in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2017 to August 2019. A total of 66 patients of proliferative lupus nephritis who need induction therapy were enrolled in this study. Leflunomide 100 mg/day for consecutive 3 days followed by 0.5 mg/kg/day in divided dose was given in experimental group (n = 32) and intravenous cyclophosphamide 0.5 gm/m2 of body surface area monthly pulse was given in control group (n = 34). All study patients have received prednisolone and hydroxychloroquine according to KDIGO guideline then followed up monthly for 6 months. Outcomes were measured at 6th month by renal function [S. Creatinine, 24 hours urinary total protein (24-hr UTP)], changes in SELENA-SLEDAI score, anti-ds DNA level, serum complement levels (serum C3 & C4), remission (complete/partial) and adverse drug responses. Result: In experimental group, remission occurred in 18 (56.3%) patients and no remission in 14 (43.7%) patients. In control group, remission occurred in 24 (70.6%) patients and no remission in 10 (29.4%) patients. Adverse effects in experimental group were: elevated ALT (6.3%), hypertension (12.5%), infection (6.3%) and amenorrhea (12.5%). In control group, adverse effects were mainly leucopenia (5.9%), infection (17.7%) and amenorrhea (29.4%). Intergroup analysis for treatment responses and adverse effects showed no significant difference (p > 0.05). Conclusion: Leflunomide combined with prednisolone is effective in the induction treatment of proliferative lupus nephritis in Bangladeshi patients in terms of response rate and adverse effects.

TUBULORETICULAR STRUCTURE AND CYLINDRICAL CONFRONTING CISTERNAE IN LUPUS NEPHRITIS

Objective.To investigate the pathological significance of tubuloreticular structure(TRS) and cylindri- cal confronting cisternae(CCC) in patients with lupus nephritis. Methods. An electron microscopical study of 24 renal biopsy specimens from patients with lupus nephritis was carried out, with particular emphasis on two endoplasmic reticulum(ER)-related structures. Result. TRS was found in 18 cases, and CCC in 10 of them. TRS often appeared in the capillary en- dothelium,and did not correlate well with the activity index of lupus nephritis. CCC appeared frequently in monocyte/macrophage and lymphocyte, and correlated well with both the activity index and the amount of interstitial immune deposits. Conclusion.TRS and CCC derived from inward "budding" of ER membrane were suggested and the morphogenesis and morphologic variations of CCC were discussed. Both TRS and CCC are pathognomonic, though not specific changes. They may be helpful in pathologic diagnosis of lupus nephritis, when properly combined with certain clinical and pathological features.

Long-Term Outcome of 102 Cases of Lupus Nephritis: A Single-Center Cohort Study in Japan

Background: The mortality rate is higher in SLE patients with lupus nephritis (LN) than in those without nephropathy. Objectives: The aim of this study was to identify the factors affecting the long-term renal outcome in 102 patients with LN. Methods: This was a retrospective cohort study. Logistic regression analysis was used in a model to determine how independent variables predicted the outcome. The survival analysis was based on the Kaplan-Meier curve with subjects censored for death. Results: The 15-year survival rate was 93.5%, and the renal function non-deterioration rate was 78.3%. No influence of individual types of immunosuppressant drugs used was found on the renal function deterioration rate. In this study, the results of analysis identified only daily urinary protein excretion level as having any significant effect on the risk of progression of LN to renal failure. Conclusions: These results suggest that remission induction therapy and maintenance therapy focused on long-term preservation of renal function need to be selected for LN patients with a high daily urinary protein value at the start of treatment and for LN patients who fail to show any reduction of the daily urinary protein excretion level to 0.5 g or less at one year after the biopsy.

Prognostic Aspects of Lupus Nephritis at Aristide Le Dantec University Hospital in Dakar

Introduction: Kidney injury is common in the course of lupus and affects the functional and vital prognosis. The risk of progression to end-stage renal failure can reach 40% to 60%. Thus we carried out this work for the purpose of an evaluation of the renal and vital prognosis and to deduce the factors of poor prognosis. Patients and method: This was a retrospective, descriptive and analytical study conducted over a period of 10 years from January 1, 2007 to December 31, 2016, performed in the Nephrology Department of Aristide Le Dantec Hospital in Dakar. Patients with lupus nephritis were included. The studied parameters were epidemiological, clinical, paraclinical and progression. We had done a crossover of the patients to look for the factors of poor renal and vital prognosis. Results: Out of 93 cases of lupus patients, 64 were included, a prevalence of 69%. The mean age of the patients was 31.97 ± 10.44 years old. There were 81% women and 19% men, a sex ratio of 0.23. Class III was found in 24 cases (37.5%), Class IV in 20 cases (31.25%), Class V in 15 cases (23.4%), Class II in 4 cases (6.25%) and Class I in 1 case (1.6%). The combination of corticosteroids and immunosuppressants was used in 56.25% of cases. After a follow-up of six months, 19 patients were in complete remission, 21 had resistance and 9 had partial remission. Of the 21 patients who had resistance, 8 were in chronic renal failure. Death was observed in 5 patients and the causes were in 3 patients: pulmonary embolism, bacterial meningitis and pulmonary tuberculosis. The cause of death was unknown in 2 patients. The factors of poor renal prognosis were lymphopenia, the presence of anti-native DNA antibodies, nephrotic syndrome, microscopic hematuria, tubular atrophy and interstitial fibrosis. Risk factors affecting renal survival were the presence of native anti-DNA antibodies, microscopic hematuria, leukocyturia and the presence of a proliferative class. The factors of poor prognosis were renal failure, lymphopenia, nephrotic syndrome, glomerular sclerosis, arteriosclerosis, interstitial infiltration and tubular atrophy. Conclusion: The risk conferred by nephropathy is greater for proliferative glomerulonephritis;it is also correlated with the presence of persistent nephrotic syndrome or severe renal failure.

Pneumothorax during retroperitoneal laparoscopic partial nephrectomy in a lupus nephritis patient:A case report

BACKGROUND Downgrading target treatment and laparoscopic partial nephrectomy have become increasingly popular in patients with renal cell carcinomas.Rare as it is,pneumothorax is one of the most severe intraoperative complications which needs immediate recognition.On the other hand,as a rheumatological disease,lupus nephritis requires a long period of hormone therapy.Cases of pneumothorax in hormone-consuming renal cancer patients are even fewer.CASE SUMMARY A 39-year-old woman was admitted to our department to take a laparoscopic partial nephrectomy.The patient had a medical history of lupus nephritis and renal clear cell carcinoma with hormone and target treatment.Her blood oxygen saturation dropped to 92%during the operation,and pneumothorax was detected by ultrasound.O2 inhalation and lung dilation were performed.Her vital signs were monitored closely throughout the operation.The operation was accomplished,and she regained consciousness smoothly.A postoperative bedside chest X-ray was conducted after she was transferred to the urosurgery ward,while no evidence of further pneumothorax or lib injury was observed.CONCLUSION Pneumothorax is a severe complication in laparoscopic or robotic-assisted laparoscopic operations,especially in retroperitoneal ones.It is easily neglected unless the injury of the diaphragm is found.Low insufflation pressure and shorter operation time are necessary for patients with a history of long-term hormone consumption or chronic immune system disease.

The gene expression of NGAL and TLR9 in glomerulus and tubulo-interstitium of patients with lupus nephritis

Background The role of neutrophil gelatinase associated lipocalin (NGAL) and Toll-like receptor 9 (TLR9) in the pathogenesis of lupus nephritis remain elusive. Methods We quantified the glomerular and tubulointerstitial mRNA expression of NGAL and TLR9 in 42 patients with lupus nephritis (LN group) and 10 controls. Results As compared to controls, LN group had higher glomerular expression of TLR9, and higher tubulointerstitial expression of NGAL and TLR9. Tubulointerstitial NGAL expression significantly correlated with proteinuria (r = 0.492;p = 0.003), renal function (r = -0.386;p = 0.022) and histological chronicity index (r = 0.540;p = 0.004). Proteinuria had significant correlation with glomerular (r = 0.554;p = 0.001) and tubulointerstitial (r = 0.379;p = 0.043) TLR9 expression. Furthermore, there was a significant difference in tubulointerstitial expression of NGAL between treatment response groups. Conclusion There is an increase in intra-renal mRNA expression of NGAL and TLR9 in LN. Although tubulointerstitial expression of NGAL does not correlate with systemic disease activity, it correlates with proteinuria, renal function, and therapeutic response. The role of NGAL in the pathogensis in LN, as well as its application as biomarker for lupus nephritis, requires further study.