Utility of serum anti-phospholipase A2 receptor antibody as a biomarker in membranous nephropathy: An experience from a tertiary care center of Eastern India

Background: Membranous nephropathy (MN) is a pattern of glomerular injury. Exact categorization into primary membranous nephropathy (PMN) or secondary membranous nephropathy (SMN) is essential for treatment. An endogenous podocyte antigen, M-type phospholipase A2 receptor (PLA2R) has been discovered to be involved in the pathogenesis of PMN. Aims and Objectives: In this article, we aimed to analyze renal tissue PLA2R and serum anti-PLA2R antibodies in MN cases and determined the diagnostic utility. Materials and Methods: The study was of prospective type carried out from March 2019 to August 2020. Analysis of cases of MN was performed with PLA2R paraffin immunoflourescence and serum anti-PLA2R antibody ELISA. Results: Overall sensitivity, specificity, PPV, and NPV of serum anti-PLA2R ELISA for PMN was 91.3%, 80%, 75%, and 93.3%, respectively, and of tissue PLA2R staining for PMN was 91.67%, 81.08%, 75.86%, and 93.75%, respectively. There was strong concordance between two methods. In the patients that were followed up, we found baseline serum anti-PLA2R antibody was less in complete remission group than that in non-remission group and the reduction in serum anti-PLA2R antibody was more in complete remission group than that in non-remission group. Conclusion: Routine light and immunofluorescence examination are incapable of giving exact categorical opinion regarding PMN and SMN. Serum anti-PLA2R antibody detection and renal tissue PLA2R analysis are sensitive and specific in detecting PMN. Baseline serum anti-PLA2R antibody and anti-PLA2R antibody quantification trends are related to prognosis of PMN. So they can be incorporated as additional biomarker.

Membranous nephropathy / Nefropatia membranosa

ABSTRACT Membranous nephropathy is a glomerulopathy, which main affected target is the podocyte, and has consequences on the glomerular basement membrane. It is more common in adults, especially over 50 years of age. The clinical presentation is nephrotic syndrome, but many cases can evolve with asymptomatic non-nephrotic proteinuria. The mechanism consists of the deposition of immune complexes in the subepithelial space of the glomerular capillary loop with subsequent activation of the complement system. Great advances in the identification of potential target antigens have occurred in the last twenty years, and the main one is the protein "M-type phospholipase-A2 receptor" (PLA2R) with the circulating anti-PLA2R antibody, which makes it possible to evaluate the activity and prognosis of this nephropathy. This route of injury corresponds to approximately 70% to 80% of cases of membranous nephropathy characterized as primary. In the last 10 years, several other potential target antigens have been identified. This review proposes to present clinical, etiopathogenic and therapeutic aspects of membranous nephropathy in a didactic manner, including cases that occur during kidney transplantation.

RESUMO A nefropatia membranosa é uma glomerulopatia, cujo principal alvo acometido é o podócito, e acarreta consequências na membrana basal glomerular. Tem maior frequência em adultos, principalmente acima dos 50 anos. A apresentação clínica é a síndrome nefrótica, mas muitos casos podem evoluir com proteinúria não nefrótica assintomática. O mecanismo consiste na deposição de complexos imunes no espaço subepitelial da alça capilar glomerular com subsequente ativação do sistema do complemento. Grandes avanços na identificação de potenciais antígenos alvo têm ocorrido nos últimos vinte anos, e o principal é a proteína "M-type phospholipase-A2 receptor" (PLA2R) com o anticorpo anti-PLA2R circulante, o que possibilita avaliar a atividade e o prognóstico dessa nefropatia. Essa via de lesão corresponde aproximadamente a 70% a 80% dos casos da nefropatia membranosa caracterizada como primária. Nos últimos 10 anos vários outros antígenos alvo potenciais têm sido identificados. Esta revisão se propõe a apresentar de modo didático aspectos clínicos, etiopatogênicos e terapêuticos da nefropatia membranosa, incluídos os casos com ocorrência no transplante renal.

Caracterización de enfermedades glomerulares: análisis de 22 años de biopsias renales / Frequency of glomerular diseases in an analysis of 550 kidney biopsies

BACKGROUND: The frequency of glomerular diseases is dynamic and varies according to geographic area. AIM: To evaluate the frequency of primary and secondary glomerulopathies, their demographic profile and main clinical characteristics. MATERIAL AND METHODS: Renal biopsies from native kidneys performed between 1999 and 2020 were retrospectively reviewed. Demographic characteristics, clinical presentation, most relevant laboratory tests, frequency of primary and secondary glomerulopathies were analyzed. RESULTS: We analyzed 550 kidney biopsies from patients with a median age of 48 years (64% females). Nephrotic syndrome was the main indication for renal biopsy. Primary and secondary glomerulopathies occurred with similar frequency. Within the primary glomerulopathies, membranous nephropathy (34.1%) was the most common, followed by IgA nephropathy (31.1%) and focal segmental glomerulosclerosis (14.1%). Among the secondary glomerulopathies, lupus nephropathy was the most common (41.7%), followed by pauciimmune glomerulonephritis (27.1%) and diabetic nephropathy (6.4%). When comparing the results with other regions, significant differences were observed with reported frequencies in United States, Europe, Asia and the rest of Latin America. CONCLUSIONS: The most common primary glomerulopathies were membranous nephropathy and IgA nephropathy. Among the secondary glomerulopathies lupus nephropathy and pauci-immune glomerulonephritis were the most common. Compared to international registries, we observed a high proportion of membranous nephropathy and pauci-immune glomerulonephritis.

Clinicopathological features and prognosis of 128 children with idiopathic membranous nephropathy / 中华实用儿科临床杂志

Objective:To analyze the clinicopathological features and prognosis of idiopathic membranous nephropathy (IMN) in children, and to investigate the factors influencing their prognosis.Methods:The clinical and pathological data of 128 children with IMN hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2019 were retrospectively analyzed.They were divided into 2 groups according to the pathological manifestations: group A[typical membranous nephropathy(MN) group] and group B (atypical MN group), and the clinicopathological characteristics of the 2 groups were compared.Different treatment regimens and their efficacy were summarized, and the prognosis and its influencing factors were analyzed.The primary endpoint event at follow-up was the occurrence of end stage renal disease (ESRD), and the secondary endpoint event was the occurrence of renal insufficiency.Children with IMN were further divided into endpoint event group and non-endpoint event group according to the presence or absence of endpoint events at the last follow-up.Survival analysis was performed using the Kaplan-Meier survival curve method.The Cox proportional risk model method was used to analyze the factors influencing the prognosis of poor kidney outcomes in children with IMN. Results:(1)A total of 128 children were included, with the male-to-female ratio of 1.13∶1.00.The median age of onset and peak age of onset were 13.0 (10.3, 15.0) years, and 12-16 years (68.8%), respectively.Massive proteinuria was detected in 119 cases (93.0%), including 103 cases (80.5%) with massive proteinuria and hematuria, 4 cases(3.1%) with simple hematuria, and 5 cases (3.9%) with non-renal proteinuria.There were 29 cases (22.7%) in group A and 99 cases (77.3%) in group B. (2)Blood triacylglycerol level was significantly higher in group B than that of group A[2.1 (1.5, 3.0) mmol/L vs.1.7(1.1, 2.5) mmol/L], while high-density lipoprotein[1.5(1.1, 1.8) mmol/L vs.1.8(1.4, 2.1) mmol/L], serum albumin[22.0(17.0, 27.3) g/L vs.25.5 (21.0, 32.5) g/L] and complement C3[(1.1±0.2) g/L vs.(1.2±0.2) g/L] were significantly lower in group B than those of group A (all P<0.05). (3)Complete clinical data during hospitalization and follow-up data were obtained from 91 children with IMN, with a median follow-up time of 87.0 (49.0, 104.5) months.Among them, 5 cases (5.5%) progressed to ESRD, involving 3 cases received renal transplantation, and 9 cases (9.9%) had secondary endpoints.Cumulative renal survival rate for ESRD at 5 and 10 years were 96.2% and 92.9%, respectively, which, for the secondary endpoints at 5 and 10 years were 95.2% and 84.8%, respectively.(4)Kaplan-Meier survival analysis showed no significant difference in the cumulative renal survival between group A and group B ( P>0.05). Multifactorial Cox regression analysis showed that tubular atrophy/interstitial fibrosis was an independent risk factor for renal insufficiency in children with IMN ( HR=0.102, 95% CI: 0.011-0.940, P<0.05). Conclusions:Massive proteinuria combined with hematuria is the major clinical manifestation of IMN in children, and atypical MN is the major pathological manifestation.Tubular atrophy/interstitial fibrosis is an independent risk factor for renal insufficiency in children with IMN.

Exploration on the TCM pathogenesis of hypersecretion of airway mucus in children base on the theory of water-liquid metabolism and triple energizer membranous system / 国际中医中药杂志

The pathological position of hypersecretion of airway mucus is in airway mucosa. Modern TCM theory believes that the airway mucosa belongs to the triple energizer membranous system of TCM, and the airway mucus is a part of TCM water-liquid system. Based on the TCM physiological characteristics of children, this article explored the pathogenesis of airway mucus hypersecretion in children, and believed that the airway mucus hypersecretion was the result of the disorder of water-liquid metabolism in TCM, which was closely related to the function of qi transformation of triple energizer membranous system. Failure of qi transformation in triple energizer is the core pathogenesis of hypersecretion of airway mucus in children. The deficiency of yang qi in children leads to the disorganization of vaporization in triple energizer, which leads to the insufficiency of movement and transformation function, the failure of water and qi in water, the stop of water and water accumulation, the abnormity of water and grain. The disorder of water-liquid metabolism leads to the occurrence of high airway mucus secretion in children.

Pharmacogenetic testing improves treatment responses in patients with PLA2R-related membranous nephropathy / 南方医科大学学报

OBJECTIVE@#To evaluate the value of pharmacogenetic testing for improving the efficacy and safety of treatment with cyclosporine, tacrolimus, and cyclophosphamide (CTX) for PLA2R-related membranous nephropathy and for determing individualized and precise treatment plans for the patients.@*METHODS@#A total of 63 patients with PLA2R-related membranous nephropathy hospitalized in the Department of Nephrology at our hospital from January, 2019 to October, 2021 were enrolled in this study. Thirty-three of the patients underwent pharmacogenetic testing before taking the immunosuppressive drugs selected based on the results of genetic screening for sensitive targets, and the other 30 patients were empirically given immunosuppressive drugs according to the guidelines (control group). The clinical efficacy and adverse effects of the immunosuppressive drugs were analyzed for all the patients. The two groups of patients were compared for demographic and biochemical parameters including 24-h urine protein, serum albumin, renal function, and serum anti-phospholipase A2 receptor antibody both before and at 3 months after the beginning of the treatment.@*RESULTS@#Among the 33 patients undergoing pharmacogenetic testing, 51.5% showed a GG genotype for cyclosporine, and 61.6% had an AG genotype for tacrolimus; for CTX, 51.5% of the patients showed a homozygous deletion and 63.6% had an AA genotype. After treatment for 3 months, serum anti-phospholipase A2 receptor antibody, 24-h urine protein, and serum albumin levels were significantly improved in pharmacogenetic testing group as compared with the control group (P < 0.05).@*CONCLUSION@#Individualized and precise administration of immunosuppressive drugs based on pharmacogenetic testing better controls proteinuria and serum antiphospholipase A2 receptor antibodies and increases serum albumin level in patients with PLA2R-related membranous nephropathy.

Mechanism of Salvianolate in Inducing Autophagy in Podocytes of Rats with Membranous Nephropathy via AMPK/SIRT1/PGC-1α Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of salvianolate on the protein expressions of adenosine monophosphate （AMP）-activated protein kinase （AMPK）， silent information regulator 1 （SIRT1） and peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α）， autophagy and apoptosis in kidney tissue of rats with membranous nephropathy （MN）， and to explore its possible molecular mechanism against MN. MethodEighty male SD rats were randomly divided into normal group， model group， benazepril hydrochloride group （10 mg·kg-1）， and salvianolate low-， medium-， and high-dose groups （16.7， 33.3 and 66.7 mg·kg-1）. The rats were modeled by injection of cationized bovine serum albumin （C-BSA） into the tail vein. After successful modeling， rats in the administration groups were given corresponding doses of drugs for 4 consecutive weeks， and then 24-hour urine， serum and kidney tissue were collected for the detection of 24-hour urinary protein （UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， C reactive protein （CRP）， glutathione peroxidase （GSH-Px）， superoxide dismutase （SOD）， and malondialdehyde （MDA）. The pathological changes of kidneys were observed by light microscope， electron microscope and immunofluorescence. Western blot was used to detect the protein expressions of phospho-AMPK （p-AMPK）， AMPK， phospho-SIRT1 （p-SIRT1）， SIRT1 and PGC-1α in rat kidney tissue. The protein expressions of autophagy-specific gene （Beclin-1）， microtubule-associated protein 1 light chain 3 （LC3） Ⅱ， ubiquitin-binding protein （p62）， B cell lymphoma （Bcl-2）， Bcl-2-associated X （Bax）， and cysteine aspartic protease-7 （Caspase-7） in rat kidney tissue were determined by immunohistochemistry （IHC）. ResultCompared with the conditions in the normal group， the levels of UTP， IL-6， TNF-α， CRP and MDA in the model group were increased （P<0.05） while the levels of SOD and GSH-Px were decreased （P<0.05）， and there was no difference in BUN and SCr. Compared with the model group， the administration groups had lowered UTP， IL-6， TNF-α， CRP and MDA （P<0.05） while elevated SOD and GSH-Px （P<0.05）. It could be seen from hematoxylin and eosin （HE） staining， Masson staining， immunofluorescence and electron microscopy that the pathological damage of rat kidney tissue in the model group was significant， but after treatment with benazepril hydrochloride and salvianolate， the pathological damage of kidney cells was gradually improved. The expressions of p-AMPK/AMPK， p-SIRT1/SIRT1， PGC-1α， Bcl-2， Beclin-1 and LC3Ⅱ in rat kidney in the model group were lower than those in the normal group （P<0.05） while the expressions of Bax， Caspase-7 and p62 were higher （P<0.05）. Compared with the model group， benazepril hydrochloride group and salvianolate groups had an up-regulation in the expressions of p-AMPK/AMPK， p-SIRT1/SIRT1， PGC-1α， Bcl-2， Beclin-1 and LC3Ⅱ in the kidney （P<0.05） while a down-regulation in the expressions of Bax， Caspase-7 and p62 （P<0.05）. ConclusionThe protective effect of salvianolate on the kidneys of MN rats may be related to the activation of AMPK/SIRT1/PGC-1α signaling pathway， the up-regulation of autophagy and the reduction of apoptosis.

Research progress on neutrophil extracellular traps in oral infectious diseases / 口腔疾病防治

@#Eutrophils are the first innate immune cells to reach the site of inflammation. Neutrophils produce neutrophil extracellular traps (NETs) that can quickly capture and limit the spread of pathogens, facilitating the removal of pathogens and their debris. Neutrophils in the oral cavity are specifically transformed from circulating neutrophils in the blood, and the number of NETs released by oral neutrophils is much higher than that of circulating neutrophils, thus better maintaining the balance of the oral microenvironment. As a bimorphic fungus, only the mycelium phase of Candida albicans can induce NETs, which is related to the neutrophils' ability to sense the size of pathogenic microorganisms through neutrophil elastase. However, spherical Staphylococcus aureus are much smaller than Candida albicans, and they can still induce NETs. Porphyromonas gingivalis, as one of the microorganisms in the periodontitis complex, induces fewer NETs than Streptococcus oralis and Actinomycetes, which are two common oral microorganisms, and there may be a mechanism allowing them to escape neutrophilic immunity in the early stage of periodontitis. Although the two main pathways of NET production have been studied in detail, the mechanisms involved in the induction of NETs by different microorganisms, especially from oral neutrophils, are not well understood. This review describes the mechanism of the immune effects of pathogenic microorganisms on neutrophil NETs in the oral cavity, providing a reference for the search for therapeutic targets and the development of key drugs for treating oral infectious diseases.

Clinical Significance of Thrombospondin Type 1 Domain-Containing 7A and Neural Epidermal Growth Factor-Like 1 Protein in M-Type Phospholipase A2 Receptor-Negative Membranous Nephropathy / 中国医学科学院学报

Objective To investigate the clinical significance of thrombospondin type 1 domain-containing 7A (THSD7A) and neural epidermal growth factor-like 1 protein (NELL1) in phospholipase A2 receptor (PLA2R)-negative membranous nephropathy (MN). Methods A total of 116 PLA2R-negative MN patients treated in Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University from 2014 to 2021 were enrolled in this study.Immunohistochemistry was employed to detect THSD7A and NELL1 in the renal tissue.The pathological characteristics,treatment,and prognosis were compared between positive and negative groups. Results The 116 PLA2R-negative MN patients included 23 THSD7A-positive patients and 9 NELL1-positive patients.One patient was tested positive for both proteins.The THSD7A-positive group showed higher positive rate of IgG4 (P=0.010),more obvious glomerular basement membrane (GBM) thickening (P=0.034),and higher proportion of stage Ⅱ MN and lower proportion of stage I MN (P=0.002) than the THSD7A-negative group.The NELL1-positive group had lower positive rates of C1q and IgG2 (P=0.029,P=0.001),less obvious GBM thickening (P<0.001),more extensive inflammatory cell infiltration (P=0.033),lower proportion of deposits on multi-locations (P=0.001),and lower proportion of atypical MN (P=0.010) than the NELL1-negative group.One patient with THSD7A-positive MN was diagnosed with colon cancer,while none of the NELL1-positive patients had malignancy.Survival analysis suggested that THSD7A-positive MN had worse composite remission (either complete remission or partial remission) of nephrotic syndrome than the negative group (P=0.016),whereas NELL1-positive MN exhibited better composite remission of nephrotic syndrome than the negative group (P=0.015).The MN patients only positive for NELL1 showed better composite remission of nephrotic syndrome than the MN patients only positive for THSD7A (P<0.001). Conclusions THSD7A- and NELL1-positive MN is more likely to be primary MN,and there is no significant malignancy indication.However,it might have a predictive value for the prognosis of MN.

Network Meta-analysis of Chinese patent medicines in treatment of idiopathic membranous nephropathy / 中国中药杂志

This study aimed to systematically evaluate the efficacy and safety of different Chinese patent medicines in the treatment of idiopathic membranous nephropathy. The relevant randomized controlled trial(RCT) was retrieved from PubMed, EMbase, Cochrane Library, CNKI, SinoMed, Wanfang, and VIP with the time interval from database inception to December 2022. The Cochrane risk of bias assessment tool was employed to evaluate the quality of the included RCT, and Stata 15.0 and GEMTC to perform the Bayesian network Meta-analysis. Finally, 51 RCTs were included, involving 9 Chinese patent medicines and 3 591 patients. The results of network Meta-analysis showed that in terms of the total effective rate and the increase in plasma albumin, the top three interventions were Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine, Bailing Capsules + conventional western medicine, and Tripterygium Glycosides Tablets + conventional western medicine. In terms of reducing 24-hour urine total protein, the top three interventions were Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine, Shenfukang Capsules +conventional western medicine, and Huangkui Capsules + conventional western medicine. In terms of reducing serum creatinine, the top three interventions were Shenfukang Capsules + conventional western medicine, Bailing Capsules + conventional western medicine, and Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine. In terms of safety, Chinese patent medicines combined with conventional western medicine had fewer adverse reactions than the control group. The results suggest that Chinese patent medicines combined with conventional western medicine can improve the therapeutic effect on idiopathic membranous nephropathy, and differentiated medications can be adopted according to the specific symptoms of patients in clinical treatment. Further validation needs to be carried out in the future with multi-center, large-sample, and high-quality RCT.

Traditional Chinese Medicine Intervention in Membranous Nephropathy Based on Podocyte Injury： A Review / 中国实验方剂学杂志

Membranous nephropathy， an autoimmune kidney disease with glomerular podocyte injury as the core mechanism， is a common pathological type of adult nephrotic syndrome and has become the main cause of end-stage renal disease in China. Podocytes are terminally differentiated cells that play an important role in maintaining the structural and functional stability of glomeruli and are molecular barriers for protein filtration. Glomerular filtration membrane injury induced by podocyte injury is an important cause of massive proteinuria. Persistent or aggravated proteinuria may prolong the course of membranous nephropathy. It is believed that podocyte destruction in membranous nephropathy is mainly related to oxidative stress， autophagy dysregulation， abnormal expression of podocyte marker proteins， chronic inflammation， epithelial-mesenchymal cell transdifferentiation， and so on. At present， western medicine mostly uses immunosuppressants and hormones for treatment according to its pathological stage， but there are certain adverse reactions. Traditional Chinese medicine （TCM） has made some achievements in the prevention and treatment of membranous nephropathy. In recent years， studies have found that many Chinese medicines can affect the occurrence and development of membranous nephropathy in different links by acting on multiple targets in the human body， with manifest advantages. This paper overviewed the podocyte injury mechanism in membranous nephropathy and summarized the treatment of membranous nephropathy with Chinese medicine monomers， compounds， and Chinese patent medicines in intervening related target pathways， aiming to provide a basis for the clinical treatment， basic research， and targeted drug development of TCM against membranous nephropathy.

Comparison of efficacy and safety of rituximab at different doses in the treatment of idiopathic membranous nephropathy / 中华肾脏病杂志

It was a retrospective cohort study. Patients diagnosed with idiopathic membranous nephropathy (IMN) and received rituximab (RTX) alone for one course of treatment during hospitalization in the Department of Nephrology of the First Hospital of Jilin University from March 2020 to March 2022 were enrolled. The patients were divided into 1 g standard treatment group (once 1 g every 2 weeks for twice) and 375 mg/m 2 experimental treatment group (375 mg/m 2 once a week for 4 weeks) according to the different methods of drug administration, and the efficacy and safety of different doses of RTX in the treatment of IMN were compared between the two groups to provide a reference for optimizing the clinical treatment protocol. The patients were followed up regularly for more than 9 months after treatment and the data were complete. A total of 69 patients were included with age of (51.7±11.8) years old, and 46 males (66.7%). There were 31 patients in the 1 g standard treatment group and 38 patients in the 375 mg/m 2 experimental treatment group. The proportion of first-treatment patients in the 1 g standard treatment group was higher than that in the 375 mg/m 2 experimental treatment group (87.1% vs. 65.8%, χ2=4.174, P=0.041). There were no statistically significant differences in the general data, clinical characteristics and baseline laboratory parameters between the two groups (all P>0.05). At the end of 3 months of treatment, 22 patients (31.9%) experienced remission, including 9 patients (29.0%) in the 1 g standard treatment group and 13 patients (34.2%) in the 375 mg/m 2 experimental treatment group ( χ2=0.211, P=0.646). At 6 months, 30 patients (43.5%) experienced remission, including 12 patients (38.7%) in the 1 g standard treatment group and 18 patients (47.4%) in the 375 mg/m 2 experimental treatment group ( χ2=0.521, P=0.470). At 9 months, 38 patients (55.1%) achieved remission, including 18 patients (58.1%) in the 1 g standard treatment group and 20 patients (52.6%) in the 375 mg/m 2 experimental treatment group ( χ2=0.204, P=0.652). At 9 months, the 24 h urine protein of 1 g standard treatment group and 375 mg/m 2 experimental treatment group decreased by 7.93 (6.24, 8.46) g and 7.45 (5.66, 8.67) g (both P<0.05), respectively, and serum albumin increased by 16.4 (15.5, 17.5) g/L and 15.5 (9.0, 15.8) g/L (both P<0.05), respectively, from the baseline value. Kaplan-Meier survival analysis result showed that there was no significant difference in the time of phospholipase A2 receptor titer decreasing to <5 RU/ml between the two groups (Log-rank χ2=3.653, P=0.056). Twenty-three non-serious adverse events occurred in the 1 g standard treatment group, involving 16 patients, and 10 non-serious adverse events occurred in the 375 mg/m 2 experimental treatment group, involving 10 patients. There was better safety in the 375 mg/m 2 experimental treatment group than that in the 1 g standard treatment group ( Fisher value=8.593, P=0.015). Both 375 mg/m 2 regimen and 1 g regimen of RTX in IMN patients are effective in relieving proteinuria and elevating serum albumin. The 375 mg/m 2 regimen of RTX has a lower incidence of adverse events compared with the 1 g regimen.

IgG4-related kidney disease complicated with membranous nephropathy in one patient with multiple metastatic lung malignancies / 中华肾脏病杂志

Here we report the diagnosis and treatment of a rare IgG4-related kidney disease with nephrotic syndrome as the first manifestation. A 62-year-old male patient, presented with edema in both lower limbs and foam urine, had a history of "lung malignant tumor with brain and lymph node metastasis". The increase of IgG4 and decrease of glomerular filtration rate were detected at admission, and the pathological consideration of renal biopsy was membranous nephropathy with IgG4-related tubulointerstitial nephritis. After the combination of low-dose glucocorticoids therapy and rituximab treatment, the patient showed good prognosis in a 9 month follow-up.

Three cases of obinutuzumab treatment for rituximab-resistant phospholipase A 2 receptor- associated membranous nephropathy / 中华肾脏病杂志

Rituximab is currently used as a first-line therapy for phospholipase A 2 receptor-associated membranous nephropathy due to its good efficacy and safety. Although the remission rate after rituximab treatment is more than 60%, nearly 40% patients still do not respond to treatment. We used obinutuzumab to treat 3 cases of rituximab resistant PLA 2R-associated membranous nephropathy. After the first dose of 1 000 mg with or without additional dose, the amount of anti-PLA 2R antibody and urinary protein decreased significantly and the adverse reactions were mild. The results show that obinutuzumab has a certain therapeutic effect on rituximab resistant PLA 2R-associated membranous nephropathy, but the time of follow-up observation is short and can only be used as individual cases, which needs to be confirmed by a large sample and high-quality prospective cohort study.

Influencing factors of early non-remission of proteinuria in patients with idiopathic membranous nephropathy / 中华肾脏病杂志

Objective:To investigate the influencing factors of non-remission of proteinuria in patients with nephrotic syndrome (NS) and idiopathic membranous nephropathy (IMN).Methods:The study was a retrospective observational study. The clinical data of patients with NS who were diagnosed as IMN by renal biopsy and serum albumin recovered normal after six months of treatment were collected from Beijing Anzhen Hospital, Capital Medical University from June 1, 2010 to January 31, 2022. Patients were divided into proteinuria remission group and non-proteinuria remission group according to whether urinary protein < 3.5 g/24 h and decreased 50% from the onset. The differences of clinical and pathological characteristics between the two groups at baseline were compared. The logistic regression model was used to analyze the influencing factors of non-remission of proteinuria.Results:Ninety-five NS patients with renal pathology of IMN were included in this study, with age of 57(43, 65) years old and 50 males (52.6%). There were 75 patients in the proteinuria remission group and 20 patients in the non-proteinuria remission group. Compared with the proteinuria remission group, the non-proteinuria remission group had higher baseline body mass index [(26.83±4.03) kg/m 2vs. (24.68±3.97) m 2, t=-2.149, P=0.034] and proportion of overweight (85.0% vs. 58.7%, χ2=4.765, P=0.029), and larger waist circumference [88.5(85.3, 101.5) cm vs. 87.0(77.5, 92.0) cm, Z=2.362, P=0.018]. Renal pathological results showed that the proportions of diabetes nephropathy (10.0% vs. 0, P=0.043) and glomerular hypertrophy (45.0% vs. 20.0%, χ2=5.227, P=0.022) were higher, and the average diameter of hypertrophic glomeruli was longer [(197.96±6.37) μm vs. (193.51±8.50) μm, t=2.029, P=0.041] in the proteinuria remission group than those in the non-proteinuria remission group. Multivariate logistic regression analysis results showed that waist circumference was an independent influencing factor of non-proteinuria remission in patients with IMN under waist circumference > 90 cm in men and >85 cm in women ( OR=1.083, 95% CI 1.005-1.168, P=0.037). Conclusion:Abdominal obesity is an independent risk factor of non-remission of proteinuria in NS patients with IMN after early treatment.

Neural epidermal growth factor-like 1 protein-related membranous nephropathy complicated with moyamoya syndrome: a case report and literature review / 中华肾脏病杂志

Except for IgA nephropathy, membranous nephropathy (MN) is the most common primary glomerulonephritis in China. Neural epidermal growth factor-like 1 protein (NELL-1) has been currently considered as one of the target antigens for diagnosis of primary MN. Moyamoya syndrome is a syndrome with clinical and imaging manifestations of moyamoya disease and possible vascular stenosis. By far, primary MN complicated with moyamoya syndrome has not been reported internationally. The paper reports a case of NELL-1-related MN complicated with moyamoya syndrome and reviews relevant literature to provide evidence for clinical diagnosis and treatment.

Clinicopathological characteristics and prognosis of idiopathic membranous nephropathy with or without C3 deposition / 中华全科医师杂志

Objective:To investigate the clinicopathological characteristics and prognosis of idiopathic membranous nephropathy (IMN) with or without C3 deposition.Methods:Clinical and pathological data of 576 patients with IMN diagnosed in Affiliated Hospital of Qingdao University from January 2017 to January 2021 were retrospectively analyzed. The patients were divided into C3 deposition group and non-C3 deposition group according to the immunofluorescence staining of C3. The clinical and pathological characteristics were compared between the two groups. Kaplan-Meier survival curve was used to compare the prognosis of the two groups.Results:A total of 576 IMN patients (male 364 (63.20%)) were enrolled, including 400 patients (69.44%) with C3 deposition and 176 patients (30.56%) without C3 deposition. Compared with the non-C3 deposition group, the levels of total blood cholesterol ( t=0.94, P=0.002) and the proportion of phospholipase A2 receptor ( χ2=9.99, P=0.002), IgG ( χ2=10.67, P=0.001), IgM ( χ2=7.00, P=0.008), IgA ( χ2=7.87, P=0.005) and C1q ( χ2=8.28, P=0.004) depositions in renal tissues was higher in C3 deposition group, while the levels of serum C3 ( t=2.87, P=0.004), albumin ( t=3.57, P<0.001) and IgG ( Z=3.55, P<0.001) were lower in C3 deposition group. There were no significant differences in other clinicopathological indicators between the two groups. The survival analysis was performed in 460 patients who were followed for>6 months, including 319 cases (69.35%) of C3 deposition and 141 cases (30.65%) of non-C3 deposition. The end point event was defined as an eGFR decline>30% or entry into end stage renal disease (ESRD). There was no statistically significant difference in treatment method between the two groups ( P>0.05). The median follow-up time was 22 (13,32) months, 327 (71.09%) patients achieved remission, and 22 patients had renal end-point events. Compared with the non-C3 deposition group, the proportion of urinary protein remission was lower ( χ2=10.85, P<0.05), the incidence of renal end-point events was higher ( χ2=5.05, P<0.05). Kaplan-Meier survival analysis showed that patients with C3 deposition had a lower cumulative remission rate (Log-rank χ2=6.68, P=0.010), and a lower cumulative renal survival than those without C3 deposition had ( χ2=5.42, P=0.020). Conclusions:Compared with patients without C3 deposition, IMN patients with C3 deposition have more severe clinical and pathological changes, lower renal cumulative remission rate, and are more likely to have poor prognosis.

Relationship between early urinary incontinence after holmium laser enucleation of the prostate and preoperative membranous urethral length / 中华泌尿外科杂志

Objective:To assess whether urinary incontinence after holmium laser enucleation of the prostate (HoLEP) is associated with membranous urethral length(MUL)on preoperative magnetic resonance imaging.Methods:The data of 96 patients who underwent HoLEP from January 2019 to April 2021 in Peking University Third Hospital were retrospectively analyzed. For all patients, the average age was (70.0±7.7) years old, the average body mass index was (23.9±2.9)kg/m 2, median pre-biopsy PSA was 3.79(2.48, 6.03)ng/ml, the average prostatic volume was (60.5±35.0)ml. 22 patients(22.9%) suffered with diabetes mellitus, and 17 patients(17.7%)had at least one time urinary retention. MUL was measured on MRI as the vertical distance from prostatic apex to the entry of the urethra into the penile bulb. All patients' median MUL was 13(11, 17)mm. The recovery of continence was followed up 2 weeks after HoLEP. The difference of age, body mass index, preoperative PSA, diabetes mellitus, urinary retention, prostate volume and MUL between urinary continence and incontinence group 2 weeks after HoLEP operation. The variables with P<0.1 were included in multivariable logistic regression to analyze the independent risk factors of urinary incontinence after HoLEP were compared. Results:All operations were successfully completed. The continence returned to normal in 72 cases (75.0%) and urinary incontinence existed in 24 cases (25.0%) in 2 weeks after surgery. There were 27 cases (37.5%) in continence group and 16 cases (66.7%) in incontinence group for those aged≥70 years. 21 cases (29.2%) in continence group and 13 cases (54.2%) in incontinence group had prostate volume ≥ 60 ml. There were 30 cases (41.7%) in continence group and 20 cases (83.3%) in incontinence group with MUL<13 mm. χ 2 test showed that age ( P=0.013), prostate volume ( P=0.027) and MUL ( P<0.001) were related to the incontinence after surgery. The age, prostate volume and MUL were included in the multivariate logistic regression analysis. Multiple logistic regression showed that MUL<13 mm( P<0.001) was independent predictor for incontinence after HoLEP. Conclusions:The incidence of urinary incontinence was high 2 weeks after HoLEP. Short MUL, which is less than 13 mm, is significantly associated with delayed recovery of urinary continence after HoLEP.

Rapid health technology assessment of 4 kinds of drugs for membranous nephropathy / 中国药房

OBJECTIVE To compare the efficacy， safety and economy of tacrolimus （TAC）， cyclosporin A （CsA）， cyclophosphamide （CTX） and rituximab （RTX） in the treatment of membranous nephropathy （MN）. METHODS Retrieved from Pubmed， the Cochrane Library， Wanfang data， CNKI and health technology assessment （HTA） official website， HTA reports， systematic reviews/meta-analysis and pharmacoeconomic studies about TAC， CsA， CTX and RTX combined with glucocorticoid in the treatment of MN were collected during the inception and Mar. 2022. After data extraction and quality evaluation， descriptive analysis was performed on the results of the included studies. RESULTS A total of 15 articles were included， involving 13 systematic reviews/meta-analysis and 2 pharmacoeconomic studies. In terms of efficacy， TAC and CsA showed significant advantages in increasing the response rate， and could improve the levels of urine protein， serum albumin， serum creatinine and serum total cholesterol. In terms of safety， the incidence of adverse reaction induced by TAC， CsA and RTX was low and the symptoms were mild. In terms of economics， CTX cost lower but caused severe adverse reaction； TAC cost higher but showed higher remission rate and good safety. CONCLUSIONS TAC combined with glucocorticoid may be the recommended scheme for MN.

Role of light and immunofluorescence microscopy to differentiate primary and secondary membranous nephropathy

Context: Membranous nephropathy (MN) causes nephrotic syndrome, mostly primary but may be associated with SLE, infections, cancer, or drug. Aims: To estimate clinical, serological, light microscopic, and direct immunofluorescence (DIF) findings to differentiate primary and secondary MN. Settings and Design: Prospective, cross-sectional, single-center study in a tertiary care hospital. Methods and Material: Total 51 cases from September 2019 to February 2020. Laboratory Data: Blood glucose, urine analysis, urea, creatinine, albumin, cholesterol, HBsAg, Anti HCV, ASO, ANA, MPO ANCA, PR3 ANCA, dsDNA, PLA2R, C3, and C4. Clinical parameters: age, sex, BP, skin lesions, arthralgia, edema, obesity. Renal biopsies examined with H and E, PAS, silver methanamine, MT stains. DIF done with IgG, IgM, IgA, C3c, C1q, kappa, and lambda. Statistical Analysis Used: Statistical software (Graph Pad PRISM 6) and Chi-square test). Results: Among 51 cases, 25 are primary and 26 are secondary MN with 22 being lupus nephritis, with 2 being post-infectious and the remaining 2 being proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGNMIDD) with kappa chain restriction. Mean age was 37 ± 12.18 and 30.69 ± 13.92 years for primary and secondary MN, respectively. Significant male preponderance in primary MN. Serum C4 significantly low in secondary MN (15.34 ± 9.59). Microscopic hematuria present in secondary MN. Mesangial and endocapillary hypercellularity are significant in secondary MN. IgG and kappa are significantly intense in primary whereas IgA, C3c, and C1q are significantly intense in secondary MN. Conclusions: Reliable differentiation between primary and secondary MN has important therapeutic implications.