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.

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.

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.

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.

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.

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.

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.

Effect of tacrolimus in idiopathic membranous nephropathy： a meta-analysis

Background The efficacy and safety of immunosuppression for idiopathic membranous nephropathy （IMN） are still controversial. Recent studies showed tacrolimus is effective in the treatment of IMN. To evaluate the efficacy and safety of tacrolimus （TAC） for IMN, we conducted a meta-analysis of published medical literatures. Methods Studies addressing the effect of tacrolimus in IMN were searched on PUBMED, EMBASE, The Cochrane Library, and ClinicalTrials.gov （March 2013）. Trials comparing tacrolimus with corticosteroid versus control group （cyclophosphamide with corticosteroid） were included. The quality of the studies was assessed using Jadad method. Statistical analyses were performed using Review Manager 5.2 and the results were summarized by calculating the risk ratio （RR） for dichotomous data or the mean difference （MD） for continuous data with 95% confident interval （CI）. Results A total of four studies （259 patients） were included. It was shown that therapy with tacrolimus plus corticosteroid had a higher complete remission rate compared to therapy with cyclophosplamide plus corticosteroid （RR=1.53, 95% CI： 1.05-2.24, P 〈0.05）, but not significant on total remission, partial remission and adverse effects. Also, no significant alterations were observed in proteinuria and serum albumin level between the two groups. During the entire follow-up period, serum creatinine level remained stable in both groups without ±50% increase in its level. Conclusions TAC is more effective than cyclophosphamide （CTX） by achieving complete remission in patients with IMN. Multi-ethnic RCTs are needed to evaluate its long-term efficacy and safety. Chin Med J 2014;127 （14）： 2693-2699

Cyclosporine treatment in idiopathic membranous nephropathy nephrotic syndrome in adults： a retrospective study spanning 15 years

Background Cyclosporine is effective in treating nephrotic syndrome （NS） with idiopathic membranous nephropathy （IMN） in adults. But high relapse rate remains a major concern. The way to manipulate cyclosporine is inconclusive. The aim of this study was to introduce the way how to titrate the cyclosporine to maintain complete remission without relapse. Methods Patients with biopsy-proven IMN with NS treated with cyclosporine for at least 1 month from 1996 to 2011 at Peking Union Medical College Hospital were reviewed. Results Mean age of the 51 eligible patients was 52 years, with 39 men. Mean proteinuria was （7.47±3.14） g/d, serum albumin （24.50±6.29） g/L, and serum creatinine （82.62±21.18） μmol/L. Cyclosporine was commenced at a mean dose of （3.46±0.63） mg·kg^-1·d^-1. Oral prednisone （0.40±0.29） mg·kg^-1·d^-1 was given concomitantly in 38 patients. Cyclosporine was administered for a median of 16 months （range 1-93 months） and stopped in non-responders by month six. By month 3 （n=47）, the number in complete remission （CR） and partial remission （PR） was 3 and 24, which shifted to 12 and 17 by month 6 （n=41）. Male gender, heavy proteinuria, low serum albumin level, and high serum creatinine level were significant determinants in poor response by month six （P 〈0.05 in all variables compared with responders）. There was a significant reversible serum creatinine increase within 25% during month 3 to 12 （P 〈0.05 in all variables compared with baseline value）. Eleven patients maintained cyclosporine for more than 24 months with a cyclosporine dose of （1.04±1.06） mg·kg^-1·d^-1. Nine patients were in CR. Renal function, systolic and diastolic blood pressure remained stable. Renal impairment （〉30% rise of serum creatinine）, secondary infection, hypertension, gingival hyperplasia and liver impairment occurred in 6, 4, 10, 4, and 1 patients, respectively. Conclusions The observation time for cyclosporine to effectively induce CR of NS in IMN adults should be at least six months. Long-term and low-dose of cyclosporine therapy is safe and effective to maintain CR in those responders.

Variants in the Promoter Region of HLA-DQA1 were Associated with Idiopathic Membranous Nephropathy in a Chinese Han Population

Background：Idiopathic membranous nephropathy （IMN） is an autoimmune disease and the leading cause of adult nephritic syndrome.HLA-DQA1 had been identified to be associated with IMN in Europeans and the result was replicated in Chinese Han population.In this study,six single nucleotide polymorphisms （SNPs） in the promoter ofHLA-DQA I and other two SNPs with IgA nephropathy were included for the association analysis.Methods：The SNPs were genotyped in 509 patients and 601 controls by the MassArray iPLEX.The quantification ofanti-phospholipase A2 receptor （PLA2R） antibodies in sera of IMN patients was performed by anti-PLA2R ELISA （lgG） kit.Results：After analysis,four SNPs were significantly associated with IMN,with rs2187668 and rs28383345 as the top two signals （P =8.42×10-4 and 2.48× 10-5,respectively）.Even under dominant model,the two SNPs were still significantly associated with IMN （P =3.50×10-3 for rs28383345 and P =6.55×10-5 for rs2187668）.After conditional study with rs2187668,rs28383345 was the only variant significantly correlated with IMN after Bonferroni correction （P =0.016）.The minor alleles of the two SNPs were also mutually exclusive in our cohort.This indicated that the two SNPs were independently associated with IMN in Chinese Han population.Levels of anti-PLA2R autoantibodies were correlated with the genotypes of the two SNPs,but not significantly （P〉0.05）.Conclusions：Our results revealed that a novel independent variant in the promoter of HLA-DQA I was associated with I MN in Chinese Han population.The locus possessed regulatory role according to the data of RegulomeDB.The exact role of the SNPs on the expression of HLAoDQA1 needs further investigation.

Effects of Jian Pi Qu Shi Formula on intestinal bacterial flora in patients with idiopathic membranous nephropathy:A prospective randomized controlled trial

Background:The incidence of idiopathic nlembranous nephropathy(IMN)has recently increased remarkably.Immune dysfunction caused by disordered intestinal flora might be an important factor affecting IMN.The Jian Pi Qu Shi Formula(JPQSF)shows promise in treating IMN.Here,we sequenced 16S rRNA genes to compare intestinal flora between patients with IMN and healthy persons.We also conducted a randomized controlled clinical trial to further compare the intestinal flora of patients with IMN treated with traditional Chinese medicine(TCM)and western medicine(WM).Methods:Among 40 patie nls with IMN treated at Department of Nephrology in Xiyuan Hospital,Chinese Academy of Traditional Chinese Medicine between July 2016 and December 2018,we compared 30 of them with 10 healthy persons(controls).The IMN group was randomly assigned to receive JPQSF(TCM)or immunosuppressant WM therapy in(n=15 per group)for 6 months.Intestinal microbiota diversity was analyzed using alpha diversity and beta diversity.Intestinal flora that significantly differed between the groups was analyzed using MetaStat.The effects and safety of the therapies were determined based on the values for plasma albumin,24-h urine protein excretion,serum creatinine,urea nitrogen,estimate glomerular filtration rate(eGFR),complete blood count,and liver enzymes.All data were statistically analyzed using Statistical Package for the Social Sciences(SPSS)20.0 statistical software.Results:Baseline characteristics did not significanlly differ between the IMN and healthy groups,or the TCM and WM groups.After six months of treatment,24-h urinary protein significantly declined in the TCM and WM groups(before and after treatment:3.24±1.74 vs.1.73±1.85 g,P<0.05 and 3.94±1.05 vs.1.91±1.18 g,P<0.05,respectively).Plasma albumin was significantly increased in the TCM group(before vs.after treatment:32.44±9.04 vs.39.99±7.03 g/L,P<0.05),but did not significantly change in the WM group(31.55±4.23 vs.34.83±9」4 g/L,P>0.05).Values for urea nitrogen,serum creatinine,and eGFR did not significanlly change in either group.The alpha diversity index for intestinal flora differed between the IMN and healthy groups,and the TCM and WM groups.Comparisons of multiple samples(beta diversity)revealed differences in intestinal flora between the IMN and healthy groups,and the TCM and WM groups.The Metastat analysis findings showed that the main genera that differed between the IMN group before treatment and the healthy group were Christensenellaceae_R-7_group,Bifidobacterium(77),Dorea,Escherichia-Shigella,Parabacteroides,Bifidobacterium,and Coprococcus_3.AfterTCM therapy,the main differential genera were Butyricimonas,Bacteroides,Alistipes,and Lachnospira,and after WM therapy,these were Ruminococcus_2,Lachnospiraceae_ND3007_group,Lachnospira,Bifidobacterium,Alistipes,and[Eubacterium]_ventriosum_group.Conclusion:Patients with IMN might have disordered intestinal flora,and JPQSF can regulate intestinal flora in patienls with IMN.