Clinical Observation of Serum Anti-PLA2R Antibody Levels in the Treatment of Idiopathic Membranous Nephropathy with Rituximab

Objective:To investigate the efficacy of rituximab in the treatment of idiopathic membranous nephropathy with varying levels of serum phospholipase A2 receptor antibodies.Methods:A total of 137 patients with idiopathic membranous nephropathy admitted to Beijing Sixth Hospital were selected.Based on their blood PLA2R antibody levels before rituximab treatment,patients were categorized into the PLA2R antibody positive group(n=94)and the PLA2R antibody negative group(n=43).They were followed up for at least 1 year,during which the efficacy,measured through 24-hour urine protein quantification and serum albumin levels,were compared between the two groups before and after treatment.Results:After 3 months of treatment,there was no significant difference in the quantitative levels of 24-hour urine protein between the two groups(P>0.05).However,after 6 and 12 months of treatment,there was a significant difference in the levels of 24-hour urine protein between the two groups(P<0.05).Additionally,after 3 months of treatment,there was a notable difference in the serum albumin levels between the two groups(P<0.05).However,after 6 and 12 months of treatment,there was no significant difference in serum albumin levels between the two groups(P>0.05).Analysis of complications in the two groups revealed that in the positive group,9 individuals experienced thrombosis,5 had infections,and 11 developed acute kidney injury(AKI).In contrast,in the negative group,5 individuals had thrombosis,2 had infections,and 3 developed AKI.There was no statistically significant difference in complications between the two groups(P>0.05).Conclusion:Serum anti-PLA2R antibody levels provide valuable insights into the clinical observation of rituximab treatment for idiopathic membranous nephropathy.They aid in understanding the disease’s pathogenesis,evaluating treatment efficacy,and predicting disease prognosis.

Successful treatment of patients with refractory idiopathic membranous nephropathy with low-dose Rituximab:A single-center experience

BACKGROUND The recognition of idiopathic membranous nephropathy(IMN)as an autoimmune disease has paved the way for the use of B-cell-depleting agents,such as Rituximab(RTX),which is now a first-line drug for treating IMN with proven safety and efficacy.Nevertheless,the usage of RTX for the treatment of refractory IMN remains controversial and challenging.AIM To evaluate the efficacy and safety of a new low-dose RTX regimen for the treatment of patients with refractory IMN.METHODS A retrospective study was performed on refractory IMN patients that accepted a low-dose RTX regimen(RTX,200 mg,once a month for five months)in the Xiyuan Hospital of Chinese Academy of Chinese Medical Sciences’Department of Nephrology from October 2019 to December 2021.To assess the clinical and immune remission data,we performed a 24 h urinary protein quantification(UTP)test and measured the serum albumin(ALB)and serum creatinine(SCr)levels,phospholipase A2 receptor(PLA2R)antibody titer,and CD19+B-cell count every three months.RESULTS A total of nine refractory IMN patients were analyzed.During follow-up conducted twelve months later,the results from the 24 h UTP decreased from baseline[8.14±6.05 g/d to 1.24±1.34 g/d(P<0.05)]and the ALB levels increased from baseline[28.06±8.42 g/L to 40.93±5.85 g/L(P<0.01)].Notably,after administering RTX for six months,the SCr decreased from 78.13±16.49μmol/L to 109.67±40.87μmol/L(P<0.05).All of the nine patients were positive for serum anti-PLA2R at the beginning,and four patients had normal anti-PLA2R titer levels at six months.The level of CD19+B-cells decreased to 0 at three months,and CD19+B-cell count remained at 0 up until six months of follow-up.CONCLUSION Our low-dose RTX regimen appears to be a promising treatment strategy for refractory IMN.

Relationship Between the Efficacy of Low-Dose Glucocorticoids Combined with Tacrolimus in the Treatment of Adult Idiopathic Membranous Nephropathy and the Level of Serum Anti-PLA2R Antibodies

Objective:To further evaluate the efficacy and safety of low-dose glucocorticoids combined with tacrolimus in the treatment of adult idiopathic membranous nephropathy(IMN)in a clinical setting.Methods:We carried out a single-center prospective study of 88 patients with IMN who were admitted into the Affiliated Hospital of Hebei University from January 2019 to December 2021,and the participants were divided into two groups based on their serum anti-PLA2R antibody levels:the negative group and the positive group.46 patients were positive for anti-PLA2R antibodies and 42 were negative.Results:After 6 months of treatment,the serum albumin,cholesterol,and 24h urine protein quantification in the anti-PLA2R negative group improved more significantly compared to the positive group(P<0.05);after 6 months of treatment,the remission rate of the positive group was significantly lower than that of the negative group,and(P<0.05);Conclusion:After treatment with tacrolimus combined with low-dose glucocorticoids,patients with idiopathic membranous nephropathy who were tested positive for anti-PLA2R antibodies had a higher overall remission rate compared those who were tested negative for serum anti-PLA2R antibodies.

Therapy of Rituximab in Idiopathic Membranous Nephropathy with Nephrotic Syndrome: A Systematic Review and Meta-analysis

Objective To investigate the efficacy and safety of rituximab(RTX) in the treatment of idiopathic membranous nephropathy(IMN) with nephrotic syndrome with a systematic review and meta-analysis.Methods Pub Med, Embase, Cochrane Library and Clinical Trials(December 2016) were searched to identify researches investigating the treatment of RTX in adult patients with biopsy-proven IMN. Complete remission(CR) or partial remission was regarded as effective therapy, and the cumulated remission rate was calculated.Results Seven studies involved 120 patients(73% were men) were included in our systematic review and metaanalysis. All were prospective observation cohort studies or matched-cohort studies, mainly came from two medical centers, and one study was multi-centric(four nephrology units in northern Italy). The creatinine clearance was more than 20 ml/(min·1.73 m2) and persistent proteinuria higher than 3.5 g/d for at least 6 months. All patients received treatment previously [44(36.7%) had immunosuppressive treatment]. In 12-and 24-month, 56%(95%CI, 0.47-0.65) and 68%(95%CI, 0.41-0.87) patients could reach remission, while 15%(95%CI, 0.09-0.23) and 20%(95%CI, 0.12-0.32) patients could reach CR. The reduction in proteinuria was gradual and obvious, paralleled with upward trend of serum albumin level and decreasing serum cholesterol level. Renal functions were stable. Relapses happened in 24 months were around 8%. RTX related adverse events were mild and were mostly infusion-related reactions.Conclusions RTX treatment in IMN was efficient, well tolerated and safe. More than 60% patients can reach partial remission or CR in 24 months, and relapse is rare. Adverse events of RTX are mostly infusion-related reactions and generally mild.

Efficacy and Safety of Tacrolimus vs. Cyclophosphamide for Idiopathic Membranous Nephropathy:A Meta-analysis of Chinese Adults

The efficacy and safety of tacrolimus （TAC） and cyclophosphamide （CTX） in the treatment of idiopathic membranous nephropathy （IMN） were compared in Chinese adult patients using a meta-analysis of the available literatures. Randomized controlled clinical trials （RCTs） of the treatment of primary IMN with TAC or CTX combined with corticosteroids in the English databases PubMed, Embase and Cochrane, as well as Chinese databases, were searched. Qualified studies were subjected to quality assessment and meta-analysis. A total of 8 RCTs, including 359 Chinese patients, were included in the meta-analysis. The complete remission rate and overall remission rate in the TAC treatment group after 6 months of treatment were higher than those in the CTX treatment group. No significant difference in remission rate was found after 12 months of treatment. There was no significant difference in the adverse reaction between the two groups at the 6th or 12th months. TAC-based treatment was associated with a faster response than CTX at the 6th month, but there was no significant difference between the two groups at 12th month in Chinese adults. Further study is needed to evaluate the long-term efficacy and safety of this treatment regimen.

Effect of Nephritis Rehabilitation Tablets combined with tacrolimus in treatment of idiopathic membranous nephropathy

BACKGROUND Idiopathic membranous nephropathy(IMN)has a high incidence in the middleaged and elderly population,and poses a great threat to the physical and mental health and quality of life of patients.Nephritis Rehabilitation Tablets have many potential effects,such as clearing residual toxins,tumefying the kidney and spleen,replenishing qi,and nourishing yin,and have played an important role in the treatment of a variety of kidney diseases.AIM To investigate the efficacy and safety of Nephritis Rehabilitation Tablets combined with tacrolimus in the treatment of IMN.METHODS Eighty-four patients with IMN recruited from January 2017 to September 2020 were randomly divided into a study group(n=42)and a control group(n=42).On the basis of routine symptomatic treatment,both groups were treated with tacrolimus,and the study group was additionally treated with Nephritis Rehabilitation Tablets.Both groups were treated for 12 wk.The therapeutic effect,the levels of renal function indexes[serum creatinine(Scr),serum albumin,and 24-h urinary protein],urinary immunoglobulin(IgG4),membrane attack complex(C5b-9),and the incidence of adverse reactions were measured before and after 12 wk of treatment.RESULTS The total effective rate in the study group was significantly higher than that of the control group.Before treatment,there was no significant difference in Scr,serum albumin,or 24 h urinary protein between the two groups.After 12 wk of treatment,the levels of Scr and 24-h urinary protein in both groups were significantly lower and serum albumin was significantly higher than those before treatment(P<0.05),and the levels of Scr and 24-h urinary protein were significantly lower(P=0.003 and 0.000,respectively),and the level of serum albumin was significantly higher(P=0.00)in the study group than in the control group.Before treatment,there was no significant difference in urinary IgG4 and C5b-9 levels between the study group and the control group(P=0.336 and 0.438,respectively).After 12 wk of treatment,the levels of urinary IgG4 and C5b-9 in the two groups were lower than those before treatment,and the levels of urinary IgG4 and C5b-9 in the study group were significantly lower than those in the control group(P=0.000).There was no significant difference in the incidence of adverse reactions between the two groups(P=0.710).CONCLUSION Based on routine intervention,Nephritis Rehabilitation Tablets combined with tacrolimus in the treatment of IMN can effectively improve the renal function of patients and downregulate the expression of urinary IgG4 and C5b-9.In addition,they can improve the overall therapeutic effect while not increasing the risk of adverse reactions.

sPLA2-IB Level Correlates with Hyperlipidemia and the Prognosis of Idiopathic Membranous Nephropathy

Summary:Recent studies suggested that serum secretory phospholipase A2 group IB(sPLA2-IB)was increased in idiopathic membranous nephropathy(IMN).However,the interference of high lipemia on the sPL.A2-IB levels was not taken into account in these studies.The present study aimed to investigate the correlation between sPLA2-IB and lipemia,and the clinical merit of sPLA2-IB in the prediction of prognosis of IMN patients.A total of 64 IMN patients,39 immunoglobulin A nephropathy(IgAN)patients and 64 healthy controls were included in the study.The levels of serum sPLA2-IB,lipemia and proteinuria were measured.Fifty IMN patients were followed up for 6 months.Pathologic stages were made for all IgAN and IMN patients.The results showed that the levels of serum sPLA2-IB,cholesterol and low-density lipoprotein cholesterol(LDL-C)were significantly higher,and the levels of albumin and high-density lipoprotein cholesterol(HDL-C)were significantly lower in IMN patients than in healthy controls and IgAN patients.Serum sPLA2-IB levels were also found to be higher in IgAN patients than in heathy controls,but the association of serum sPLA2-IB levels with proteinuria,cholesterol and albumin was only shown in IMN patients.Antibody against M-type receptor for secretory phospholipase A2(PLA2R1)was positive in 813%IMN patients.Glomerular sPLA2-IB deposition,podocyte fused processes,and density deposition on thickened basement membrane were seen in IMN patients,but not in IgAN patients.IMN patients with lower sPLA2-IB and proteinuria levels were found to have better outcome after the 6-month follow-up.In IMN patients,sPLA2-IB levels were significantly increased in both serum and renal tissue.In conclusion,serum sPLA2-IB was closely correlated with proteinuria,albumin and cholesterol,and IMN patients with lower sPLA2-IB levels were more likely to achieve a better outcome.

STUDY ON THE RELEVANCY OF IDIOPATHIC MEMBRANOUS NEPHROPATHY TO HLA HAPLOTYPE IN SHANGHAI POPULATION

Objectire To disclose the relevancy of idiopathic membranous nephropathy (IMN) to HLA haplotype in Shanghai region population. Methods Analysis of HLA genotype and haplotype was carried out in 33 IMN patients and 71 controls in Shanghai using PCR - SSO. Rcsults The normal haplotypes of controls were DR9- DQA1 * 0301, DR4 - DQA1 *0301, DR12- DQB1 * 0301 and DR9- DQB1 * 0303. The haplotype frequency (Hf) of DR2- DQA1 * 0101 was the highest in IMN group (Hf=12.86), presenting significant linkage disequilibrium. The dofference between two groups was significant (P<0.05). Conclusion It was concluded that the susceptibility of IMN in Shanghai population was associated with specific HLA haplotype.

Idiopathic membranous nephropathy in children:A case report

BACKGROUND Minimal change disease is a common cause of nephrotic syndrome(NS) in children and has a good prognosis. Idiopathic membranous nephropathy(IMN), a rare cause of NS in children, may progress to chronic kidney disease. However, there is little data on how to evaluate and treat IMN in children.CASE SUMMARY In this article, we report the case of a 7-year-old boy with steroid-resistant NS. After cyclophosphamide pulse therapy combined with oral prednisone, the urinary protein results remained positive. Renal biopsy confirmed the pathological diagnosis of stage Ⅱ MN, with positivity for phospholipase A;receptor. Other immunological and infectious diseases relevant to secondary MN were ruled out by laboratory tests. Subsequently, tacrolimus plus prednisone was administered, and the therapeutic effect was satisfactory.CONCLUSION IMN is rare in children. The main clinical manifestation is NS. The diagnosis depends on renal biopsy. There is little evidence-based data on the treatment of IMN in children. Therefore, large-sample randomized controlled trials need to be performed. Individualized treatment should be used to improve the prognosis of the disease.

Non-glomerular Tip Lesion Focal Segmental Glomerulosclerosis as a Negative Predictor in Idiopathic Membranous Nephropathy

Objective To assess the significance of focal segmental glomerulosclerosis(FSGS)variants on clinicopathological characteristics and short-term outcomes in idiopathic membranous nephropathy(IMN)patients.Methods The clinicopathological data of 146 IMN patients diagnosed between December 2016 and March 2019 in our center were collected and analyzed.These patients were divided into the pure IMN group,IMN with glomerular tip lesion(GTL)group,and IMN with non-GTL FSGS group.Results The IMN with non-GTL FSGS and IMN with GTL groups both had higher proportions of patients with hypertension,lower serum albumin,and severe proteinuria,while the IMN with non-GTL FSGS group additionally showed higher blood pressure and serum cholesterol,and lower serum IgG than the IMN group(all P<0.05).As for pathology,the IMN with non-GTL FSGS group had higher proportions of patients with acute tubular injury and moderate to severe chronic injuries than the IMN group(all P<0.05).In the IMN,IMN with GTL,and IMN with non-GTL FSGS groups,the overall one-year remission rates were 81.6%,76%,and 58.8%,respectively.Furthermore,the IMN with non-GTL FSGS group showed the lowest cumulative incidence to reach remission within one year.Multivariate Cox logistic analysis demonstrated that higher level of serum anti-M-type phospholipase A2 receptor antibody and the existence of non-GTL FSGS lesion were independent predictors for no remission in IMN patients.Conclusion The non-GTL FSGS lesion was a novel negative predictor in IMN and should be taken into account in the management of IMN.

IL-4, IL-10 and TNF-<i>α</i>Polymorphisms in Idiopathic Membranous Nephropathy (IMN)

Idiopathic membranous nephropathy (IMN) is a Th2 nephritogenic immune disorder. It is caused by the accumulation of immune complexes, mainly IgG4, at the basal glomerular membrane that leads to the damage of the glomerular barrier and subsequent injury of podocytes. Our aim was to evaluate the relationship between cytokine polymorphisms and IMN. We investigated the cytokine polymorphisms in forty-five patients and one hundred twenty-four healthy individuals, using polymerase chain reaction-sequence specific primers (PCR-SSP). We showed a significant increase in allelic frequencies of the alleles -590T and -33T of IL-4 gene and -308A of TNF-α gene, in IMN patients. In addition, we observed an increased frequency of allele -1082G in IL-10 gene in a subgroup of patients with CD4/CD8 ratio major than 2, when compared either to control subjects or the subgroup of patients with CD4/CD8 ratio minor than 2. Moreover, analyzing the Th1/Th2 cytokines in serum and urine, we found increased levels of IL-4 in serum and IL-5 in urine of patients. We deduce that the alleles -590T and -33T of IL-4 and -308A of TNF-α may be associated with IMN. In addition, in patients with increased T helper lymphocytes, IL-10 -1082G polymorphism can also play a role in the pathogenesis of the disease. These findings remark the role of Th2 immune response and suggest the association between polymorphic variants of IL-4, IL-10 and TNF-α genes with the development of IMN and therefore giving a better insight in pathogenesis of this disease.

Clinical effect of enriching qi, activating blood circulation, clearing away dampness and heat combined with western medicine in the treatment of idiopathic membranous nephropathy: A meta-analysis

Objective:To systemically review the efficacy and safety about the method of enriching qi,activating blood circulation,clearing away dampness and heat combined with western medicine in the therapy of patients with idiopathy membranous nephropathy(IMN).Methods:We collected the randomized controlled trials(RCTs)of enriching qi,activating blood circulation,clearing away dampness and heat for the treatment of IMN from Pub Med,The Cochrane Library,Medline,China National Knowledge Infrastructure(CNKI),China Biology Medicine disc(CBM),Wanfang Data and Wiper Databases.Bias of risk of retrieval literature was evaluated according to Cochrane Collaboration standard,and Review Manager 5.3 software was used for statistical analysis.Results:Fourteen trials(836 participants)were included in the meta-analysis.This kind of traditional Chinese method combined with western medicine in the treatment of IMN exerted statistical differences in reducing 24-hour urinary protein[WMD=-0.97,95%CI(-1.30,-0.65),Z=5.86(P<0.00001)]and elevating serum albumin[WMD=3.83,95%CI(2.10,5.57),Z=4.33,P<0.0001],lowering serum cholesterol[WMD=-0.82,95%CI(-1.08,-0.56),Z=6.18,P<0.00001],triglycerides[WMD=-0.39,95%CI(-0.67,-0.11),Z=2.77,P=0.006]and reducing the risk of adverse events[OR=0.29,95%CI[0.16,0.50],Z=4.35,P<0.0001]in the patients with IMN as compared with controls.However,there was no statistically significant difference between the method and controls when combining all trials in serum creatinine[WMD=-5.52,95%CI(-18.06,7.03),Z=0.86,P=0.39],when combining all trials in urea nitrogen[WMD=-0.90,95%CI(-2.22,0.41),Z=1.35,P=0.18].Conclusion:The method of enriching qi,activating blood circulation,clearing away dampness and heat combined with western medicine exerts certain advantages and better safety in treating patients with IMN.However,for the inferiority of the included studies,the conclusion still needs high-quality and large-sample prospective randomized controlled trials to verify.

Research progress on markers of urine tubular damage in idiopathic membranous nephropathy

Idiopathic membranous nephropathy is a common primary glomerular disease.Recently,it has been found that the progression and prognosis of glomerular diseases are not only related to the glomeruli itself,but also to the severity of renal tubular injury.Although blood creatinine and urinary protein are recognized biomarkers,they appear late,are insensitive,lack specificity,and are difficult to respond to IMN conditions in a timely and accurate manner.Markers such as N-acetyl-β-D-glucosaminidase,kidney injury molecule 1,neutrophil gelatinase-associated lipoprotein in urine can dynamically reflect the progress of kidney injury in the early stage,and are detected as noninvasive,so It has been applied in IMN,but such research is lacking,and the scope needs to be further expanded and discussed in depth.

CiteSpace-based Knowledge Graph Analysis of the Current Status and Trends of Chinese Medicine Research in Idiopathic Membranous Nephropathy

Objective:To analyze the current status and development trend of Chinese medicine research in the field of idiopathic membranous nephropathy since 2000.Methods:The literature related to Chinese medicine for idiopathic membranous nephropathy published in China Knowledge Network(CNKI)since 2000 was searched,and CiteSpacewas applied to visualize the publication time,authors,and keywords of the literature and to draw a visual knowledge graph.Results:372 relevant literatures were included.Author analysis showed that there were 343 authors included,and the authors with the highest number of publications published 13 articles,and the core authors accounted for 10.2%of the total number;keyword analysis showed that 15 clusters were formed after burst analysis,and 10 emergent words were formed after keyword emergence analysis.Conclusion:Chinese medicine recognizes and intervenes in idiopathic membranous nephropathy in terms of evidence type,treatment method,common prescriptions and single herbs,auxiliary examination,treatment modality,and clinical research.The development trend lies in the combination of macroscopic and microscopic,the synergy between Chinese and Western,multidisciplinary collision diagnosis and treatment,as well as the use of Chinese medicine to intervene in the disease process at an early stage,and the integration of a worldwide standardized diagnosis and treatment guideline of Chinese medicine for idiopathic membranous nephropathy.

Unusual Case of Idiopathic Membranous Later Developing Non-Hodgkin’s Lymphoma

A 30-year-old male presented to nephrology services as a case of nephrotic syndrome and membranous nephropathy was found on renal biopsy. He was treated for this pathology with steroid and cytotoxic drugs and remained in remission for 3 years and then presented with non Hodgkin’s lymphoma.

Cyclosporin A treatment for idiopathic membranous nephropathy

Objective To evaluate the efficacy of cyclosporin A (CSA) in the treatment of idiopathic membranous nephropathy (IMN), a prospective controlled clinical study was performed. Methods This study included a group of 30 IMN patients, among them 15 were treated with CSA and 15 with captopril (CAP). The diagnosis of IMN was made with exclusion of secondary forms of membranous nephropathy by extensive clinical and pathological studies. No patients received steroids or cytotoxic agents for six months prior to enrollment. In the CSA group, CSA was given at an initial dosage of 5mg*kg-1*d-1, gradually tailed off over the first three months and maintained at 2mg*kg-1*d-1 for 12 months. In the CAP group, CAP was given at a dosage of 37.5mg/day. Results In the first three months, 6 (6/15)complete remissions (CR) and 2 (2/15) partial remissions (PR) were observed in the CSA group while only 2 (2/15) PRs were observed in the CAP group. Before the end of the 15-months, 8 patients in the CSA group experienced CR and 4 patients experienced PR. One CR patient relapsed as the dosage of CSA was reduced, so 7 patients remained in CR at the end of the first 15-months. No additional CR or PR was observed in the CAP group during late follow-up. At the last visit (an average follow-up time of 44 months) in the CSA-group, another 2 CR patients had relapsed and 1 CR patient shifted to PR after stopping the CSA treatment, so 4 CR and 5 PR remained in the CSA group. In the CAP group, 3 spontaneous CRs occurred beyond 1.5 year's follow-up, with 3 CR and 2 PR at the last visit. No difference was found between the averages of the initial and the last serum creatinine levels in either group. No serious adverse effects were found during CSA treatment. Re-biopsy data of three patients responsive to CSA treatment showed that no pathological improvement of glomerular basement membrane was observed, even in cases at remission. Tubulointerstitial fibrosis was found in 1 relapsed CR patient, whoseserum creatinine increased above the normal range, but not in the other 2 patients whose serum creatinine remained in the normal range. Conclusions CSA therapy at a dosage of 5mg*kg-1*d-1 is effective in inducing remission of nephrotic syndrome in adult IMN patients within three months, with a response rate of 80%. A relatively high rate of relapse (50%) was observed within 2 years after the withdrawal of CSA treatment.

基于CiteSpace和VOSviewer软件分析中医药治疗特发性膜性肾病研究的现状及趋势

目的基于CiteSpace和VOSviewer可视化分析中医药治疗特发性膜性肾病的研究现状和发展趋势,为未来研究方向提供参考和建议。方法检索中国知网(CNKI)、维普(VIP)、Web of ScienceTM核心合集数据库从建库至2022年12月1日期间发表的以中医药治疗特发性膜性肾病的相关文献,并根据纳入和排除标准进行文献筛选。共纳入中文文献469篇、英文文献36篇,利用CiteSpace 6.1.R3和VOSviewer 1.6.18绘制中医药治疗特发性膜性肾病的知识图谱,对发表时间、研究作者、研究机构、研究关键词进行频数分析、聚类分析、突现分析。结果分析可得年发文量从2016年开始呈大幅度上升趋势,王暴魁是中文文献发文量最多的作者,WANG L(王琳)是英文文献发文量最多的作者;首都医科大学附属北京中医医院团队、上海中医药大学附属龙华医院为领头机构;疾病、病机、治疗为主要研究内容。研究者对名医经验的关注度高,“辨证论治”为近两年热点并有望得到进一步研究和应用。结论未来多中心多元交叉研究网络的构建、高质量真实世界研究和生物机制研究的开展将推动中医药治疗特发性膜性肾病的多维度研究得到进一步深化。

NLRP3炎症小体参与特发性膜性肾病发生的研究

目的:探讨核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎症小体在特发性膜性肾病(IMN)中的作用及其激活的可能机制。方法:收集未行肾上腺皮质激素及免疫抑制剂治疗且肾组织活检诊断为IMN的患者135例,10例因肾结核及肾肿瘤行肾切除的患者肾脏组织作为对照组。免疫组化法检测各肾组织样本NLRP3、肿瘤坏死因子受体相关因子6(TRAF6)、Caspase-1、NF-κB p65、MAPK信号通路相关蛋白磷酸化ERK1/2(p-ERK1/2)、磷酸化p38(p-p38)及磷酸化JNK(p-JNK)因子表达;收集IMN患者血液和24 h尿液,分析24 h尿蛋白定量、血肌酐、肌酐清除率、尿素氮等一般临床资料,对尿蛋白与NLRP3、Caspase-1、IL-1β、TNF-α及NLRP3与TRAF6进行相关性分析。结果:与对照组比较,IMN患者24 h尿蛋白和血肌酐明显升高(均P<0.05),肾组织NLRP3和Caspase-1蛋白表达明显升高(均P<0.05),其中Ⅱ期IMN患者肾组织NLRP3和Caspase-1蛋白表达最高,IL-1β和TNF-α表达增强(均P<0.05),其中Ⅱ期IMN患者肾组织IL-1β和TNF-α蛋白表达最强,NF-κB p65、p-ERK1/2、p-p38和p-JNK蛋白表达升高(均P<0.05)。IMN患者24 h尿蛋白与肾组织NLRP3蛋白表达呈正相关(r=0.689,P<0.01),与Caspase-1蛋白呈正相关(r=0.614,P<0.0001),与IL-1β呈正相关(r=0.708,P<0.0001),与TNF-α呈正相关(r=0.594,P<0.01)。结论:TRAF6通过NF-κB激活诱导ERK1/2、p38、JNK信号通路刺激NLRP3炎症小体活化,促进IMN发生和大量尿蛋白产生。

TIPE2在IMN中的变化及其与巨噬细胞极化相关细胞因子及IL-17/IL-10的关联研究

目的:搜集IMN病例标本,检测TIPE2的表达水平,研究其与IMN引起巨噬细胞极化相关细胞因子及IL-17/IL-10的关联。方法:选取IMN患者60例为IMN组,招募健康受试者50例为对照组。2组TIPE2水平按文献方法测定,TNF-α、IL-2、IL-17和IL-10水平采用ELISA法检测。结果:IMN组血和尿β_(2)-微球蛋白含量、尿蛋白指标均高于对照组、肌酐水平低于对照组(P<0.001)、而TIPE2、TNF-α、IL-2水平和IL-17/IL-10比值显著高于对照组(P<0.001);TIPE2水平与TNF-α、IL-2、IL-17/IL-10值均呈正相关(P<0.001)。结论:本研究可为临床治疗及药物研发提供新的方向,为基础分子参与的免疫调节提供依据。

特发性膜性肾病患者Nomogram预测模型的构建

目的通过Nomogram列线图建立一个用于预测特发性膜性肾病患者预后的模型。方法选择2018年1月~2020年12月在承德医学院附属医院首次住院并行肾穿刺活检术确诊为特发性膜性肾病(IMN)的初诊初治患者195例,并进行24个月的随访。根据随访结束时是否出现肾终点事件,将患者分为2组,分别为肾脏终点组和未达到肾脏终点组。将纳入单因素Logistic分析中P<0.2的影响因素进行多因素Logistic回归分析,按照赤池信息准则(AIC)选取最优Logistic回归模型构建IMN患者预后不良的预测模型。结果用于预测IMN预后不良预测模型的预测因子包括:年龄、平均动脉压、肾穿刺前病程、白蛋白、血肌酐。IMN患者的受试者工作特性曲线下面积(AUROC)为0.729。校准曲线的Hosmer-Lemeshow检验的统计值为1.44(P=0.49)。决策曲线(DCA)显示IMN的预测概率值在0.17至0.44之间时本模型临床适用。结论本研究构建了用于预测IMN患者预后不良的预测模型,该预测模型的预测能力、校准能力和临床净获益良好,有助于预测IMN患者的预后。