Adult Idiopathic Membranous Nephropathy Research Articles

Quantitative detection and prognostic value of antibodies against M-type phospholipase A2 receptor and its cysteine-rich ricin domain and C-type lectin domains 1 and 6-7-8 in patients with idiopathic membranous nephropathy.

M-type phospholipase A2 receptor (PLA2R) is the major autoantigen in adult idiopathic membranous nephropathy (IMN). Although reactive epitopes in the PLA2R domains have been identified, the clinical value of these domains recognized by anti-PLA2R antibodies remains controversial. Accordingly, this study aimed to quantitatively detect changes in the concentrations of different antibodies against epitopes of PLA2R in patients with IMN before and after treatment to evaluate the clinical value of epitope spreading. Highly sensitive time-resolved fluorescence immunoassay was used to quantitatively analyze the concentrations of specific IgG and IgG4 antibodies against PLA2R and its epitopes (CysR, CTLD1, CTLD6-7-8) in a cohort of 25 patients with PLA2R-associated membranous nephropathy (13 and 12 in the remission and non-remission groups, respectively) before and after treatment, and the results were analyzed in conjunction with clinical biochemical indicators. The concentration of specific IgG (IgG4) antibodies against PLA2R and its epitopes (CysR, CTLD1 and CTLD6-7-8) in non-remission group was higher than that in remission group. The multipliers of elevation of IgG (IgG4) antibody were 5.6(6.2) fold, 3.0(24.3) fold, 1.6(9.0) fold, and 4.2(2.6) fold in the non-remission/remission group, respectively. However, the difference in antibody concentrations between the two groups at the end of follow-up was 5.6 (85.2), 1.7 (13.1), 1.0 (5.1), and 1.5 (22.3) times higher, respectively. When detecting concentrations of specific IgG antibodies against PLA2R and its different epitopes, the remission rate was 66.67% for only one epitope at M0 and 36.36% for three epitopes at M0. When detecting concentrations of specific IgG4 antibodies against PLA2R and its different epitopes, the remission rate was 100.00% for only one epitope at M0 and 50.00% for three epitopes at M0. A trivariate logistic regression model for the combined detection of eGFR, anti-CTLD678 IgG4, and urinary protein had an AUC of 100.00%. Low concentrations of anti-CysR-IgG4, anti-CTLD1-IgG4, and anti-CTLD6-7-8-IgG4 at initial diagnosis predict rapid remission after treatment. The use of specific IgG4 against PLA2R and its different epitopes combined with eGFR and urinary protein provides a better assessment of the prognostic outcome of 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.

The efficacy and safety of Sanqi Qushi Granule in patients with idiopathic membranous nephropathy ——protocol of a multicenter, randomized control trial (SQ-AUTUMN)

BackgroundAdult nephropathy is mainly caused by idiopathic membranous nephropathy (IMN). In cases of proteinuria, Modified Ponticelli Regimens (MPR) are often successful. However, it can cause adverse side effects. Oral Sanqi Qushi Granule (SQG) with MPR is effective in patients with IMN. However, whether it can improve the remission rate of IMN and shorten the remission time is unknown. In this trial, SQG with MPR on IMN will be evaluated clinically for its efficacy and safety.MethodsWe will randomly assign IMN patients who meet the criteria to receives SQG plus cyclical Cyclophosphamide (CTX)/steroids or with placebo plus cyclical CTX/steroids for 6 months. A 12-month follow-up will be conducted on them. Status of remission will be used to assess treatment efficacy.DiscussionThis study aims to appraise whether treatment with SQG plus cyclical CTX/steroids is superior to placebo plus cyclical CTX/steroids in the remission rate of patients with adult IMN. Adverse events of SQG plus MPR will be also evaluated for further researches about Chinese Medicine and MPR on whether it can improve the remission rate of IMN in half a year and shorten the remission time and relieve adverse effects will also be clarified.Trial registrationChinese Clinical Trial Registry ChiCTR2200061953. Registered on 13 July 2022.

Efficacy of low or heavy rituximab‑based protocols and comparison with seven regimens in idiopathic membranous nephropathy: a systematic review and network meta-analysis.

Numerous studies have demonstrated the efficiency of tacrolimus + rituximab and rituximab in idiopathic membranous nephropathy (IMN). But optimal dosages of rituximab for IMN are still controversial. This network meta-analysis (NMA) was conducted to compare the efficacy of different rituximab dosages and other main treatments in IMN treatment. Randomized controlled trials (RCTs) and observational studies analyzing nine therapeuticregimens for IMN were included from some databases. Network comparisons were performed to analyze the rates of total remission (TR) and relapse rate. The surface under the cumulative ranking area (SUCRA) was calculated to rank interventions. Twelve RCTs and 12 observational studies involving 1724 patients were pooled for comparison of 9 interventions. This NMA demonstrated steroids + tacrolimus was ranked first in the aspect of total remission at 6months (92%) and 12months (81.3%). The total remission rate associated with tacrolimus + rituximab increased rapidly between the sixth (SUCRA 22.5%) and the twelfth month (SUCRA 63.9%). Tacrolimus and cyclosporine A were associated with higher total remission at 6months (78.8% and 65.4%, separately) and decreased at 12months (58.1 and 34.9%, separately). Steroids + cyclophosphamide, rituximab (Heavy dose) and rituximab (Low dose) had stable remission rates at 6 (63.7%, 46.6%, and 19.4%) and 12months (SUCRA 66.9%, 39.6%, and 28.8%). Tacrolimus and cyclosporine A were associated with a significantly higher risk of relapse than that with steroids + cyclophosphamide, rituximab (Heavy dose), and rituximab (Low dose). For IMN in adults, steroids + tacrolimus was ranked first in the aspect of total remission, followed by steroids + cyclophosphamide and steroids + cyclosporine A. The TR associated with rituximab (Heavy and Low dosage) at 12months was higher than that at 6months. And rituximab (Heavy dose) achieves a higher rate of total remission than that of rituximab (Low dose).

Chinese medicinal herbs for idiopathic membranous nephropathy in adults with nephrotic syndrome: A systematic review of effectiveness and safety.

To assess the benefits and harms of Chinese medicinal herbs formulae for the treatment of idiopathic membranous nephropathy in adult patients with primary nephrotic syndrome.Only randomized controlled trials were included. We searched the Cochrane Central Register of Controlled Trials database, PubMed, EMBASE, Chinese National Knowledge Internet, Chinese Biomedicine Database, and VIP. All studies were analyzed using the criteria of the Cochrane Handbook and were assessed in terms of quality and the risk of bias. Review Manager ver. 5.3.5 software was used for the data analysis, and GRADE profiler software was employed to evaluate quality.Two studies were included (n = 126 Chinese participants). We found that compared with against conventional treatment, one Chinese medicinal herbs formula plus conventional treatment reduced 24-hours urinary total protein (mean differences –3.16 g/24 h, 95% confidence intervals –4.03 to –2.29), and two Chinese medicinal herbs formulae increased serum albumin levels (mean differences 3.18 g/L, 95% confidence intervals 1.12 to 5.52; I2 = 0%).Chinese medicinal herbs formulae may reduce 24-hours urinary total protein and increase serum levels of albumin. However, larger and multicenter studies with high methodological quality are still needed.

Dysbiosis of Gut Microbiota in Adult Idiopathic Membranous Nephropathy with Nephrotic Syndrome

Dysbiosis of Gut Microbiota in Adult Idiopathic Membranous Nephropathy with Nephrotic Syndrome

Meta-Analysis of the Diagnostic Efficiency of THSD7A-AB for the Diagnosis of Idiopathic Membranous Nephropathy.

Thrombospondin type I domain‐containing 7A (THSD7A), is a specific autoantigen of adult idiopathic membranous nephropathy (IMN), whose circulating antibody (THSD7A‐AB) represents a promising biomarker for diagnosis of IMN. The objective of this meta‐analysis is to investigate the diagnostic efficiency of THSD7A‐AB for IMN. After rigorous data extraction, quality assessment, and data analysis, 10 articles (4545 patients) are included. For IMN, the summary sensitivity is 4% (2–7%), and the specificity is 99% (98–100%). The summary positive likelihood ratio (PLR) and negative likelihood ratio (NLR) are 5.40 (2.40–11.90) and 0.97 (0.95–0.99), respectively. The diagnostic odds ratio (DOR) is 6.00 (2.00–12.00). The area under the summary receiver operating characteristic curve (AUC) is 0.78 (0.74–0.81). For M‐type phospholipase A2 receptor (PLA2R)‐negative IMN, the summary sensitivity is 8% (6–10%), specificity is 100% (99–100%). The summary PLR and NLR are 15.80 (5.70–44.00) and 0.93 (0.91–0.95), respectively. The DOR is 17.00 (6.00–48.00). The AUC is 0.99 (0.98–1.00). THSD7A‐AB has higher diagnostic value in PLA2R‐negative patients than in IMN patients. These results suggest that THSD7A‐AB could possibly be applied as an auxiliary non‐invasive diagnostic method for PLA2R‐negative IMN.

Dysbiosis of gut microbiota in adult idiopathic membranous nephropathy with nephrotic syndrome

BackgroundGut bacterial microbiota is altered in patients with chronic kidney disease (CKD) and those on dialysis. However, it is not yet clear what bacterial composition changes occur in patients with idiopathic nephrotic syndrome (INS). We present in this report the changes in gut bacterial microbiota in INS patients with membranous nephropathy. MethodsA total of 158 individuals were recruited for this study. Of these, 80 patients had stage 3–5 CKD without nephrotic syndrome (CKD group), 48 patients had INS and pathological diagnosis of membranous nephropathy (INS group), and 30 were age- and sex-matched healthy controls (HC group). The gut microbiome composition was analyzed using a 16S ribosomal RNA gene-based sequencing protocol. ResultsThe results indicate that the nephrotic syndrome patients had a significantly different alpha and beta diversity compared with the CKD group and HC group (P < 0.01). At the phylum level, the INS patients showed increased Fusobacteria and Proteobacteria but reduced Firmicutes when compared with the HC group. At the genus level, Megamonas, Megasphaera, Akkermansia, and the butyrate-producing bacteria Lachnospira, Roseburia, and Fusobacterium were more abundant in the HC group (LDA score > 3) than the CKD and INS group. Fecal organic acid analysis revealed significantly lower quantities of propionate acid and butyric acid in INS than the HC group (P < 0.05). Compared with the HC group, we found that Parabacteroides was increased in CKD and INS patients. In addition, Oscillospira and Ruminococcus were more abundant in CKD patients than in the other two groups (LDA score > 3). At the genus level, ten bacterial taxa were more prevalent in the HC group. Providencia and Myroides were more prevalent in INS patients. ConclusionOur findings highlight that, INS patients had a significantly different alpha and beta diversity and decreased gut microbiota-derived short-chain fatty acids, such as butyrate. However, large-scale prospective studies should be performed to identify the cause and effect factors of these changes in the microbiota in INS patients.

Treatment of idiopathic membranous nephropathy in adults: KDIGO 2012, cyclophosphamide and cyclosporine A are out, rituximab is the new normal.

The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines for glomerulonephritis shed light on the complex world of glomerulonephritis therapy. However, they may no longer apply to idiopathic membranous nephropathy, as recently concluded by the KDIGO 2019 Working Group. This is due to the discovery of autoantibodies such as anti-phospholipase A2 receptor (anti-PLA2R) that allow disease monitoring as well as to results from recent clinical trials, comparative cohort studies and meta-analyses. Perhaps the most disruptive of them is the Membranous Nephropathy Trial of Rituximab (MENTOR) trial comparing rituximab with cyclosporine A, which supports the superiority of rituximab in efficacy and safety. Furthermore, rituximab results compared favourably with the short-term results of classical clinical trials that supported the KDIGO 2012 recommendation of immunosuppressive cyclophosphamide-based regimens as first choice for active treatment of idiopathic membranous nephropathy. Thus, the KDIGO recommendations for cyclophosphamide-based regimens or calcineurin inhibitors as the first line of active treatment regimens for idiopathic membranous nephropathy with nephrotic syndrome may no longer apply. By contrast, rituximab-based regimens or other B-cell-targeted therapies appear to represent the present and future of membranous nephropathy therapy.

Comparative efficacy of 13 immunosuppressive agents for idiopathic membranous nephropathy in adults with nephrotic syndrome: a systematic review and network meta-analysis

ObjectivesThis study aimed to compare the effectiveness of 13 types of immunosuppressive agents used to treat idiopathic membranous nephropathy (IMN) in adults with nephrotic syndrome.DesignSystematic review and network meta-analysis.Data sourcesPubMed,...

New progress in the pathogenesis, diagnosis and treatment of adult idiopathic membranous nephropathy

在绝大多数IMN患者肾组织中存在PLA2R、血清中存在抗PLA2R抗体。研究肾移植术后的复发性和新发性MN与抗PLA2R抗体的相关性，有利于进一步揭示MN的发病机制。抗PLA2R抗体的高表达与IMN的自发缓解率低、治疗抵抗率高、大量蛋白尿、肾功能受损有密切相关性。

SAT-005 PLA2R+VE MEMBRANOUS GLOMERULONEPHRITIS PATIENTS SHOWS POOR RESPONSE TO TACROLIMUS PLUS PREDNISOLONE THERAPY COMPARED TO PLA2R-VE PATIENTS

Idiopathic Membranous Nephropathy (IMN), an autoimmune concomitant nephrotic syndrome of the adult is mainly associated with PLA2R antibody expressed on podocytes. The lack of exact mechanisms involved in the pathogenesis of IMN is transmitted to its therapeutic management. There is no standard therapy for patients with frequent relapsing or steroid-dependent IMN. Hence we propose the efficacy of low dose Tacrolimus (Tac) plus prednisolone and associated changes in anti-PLA2R in adult IMN. Total 101 membranous nephropathy patients were treated with combination of prednisolone 1mg/kg alt-day) and Tac 0.1mg/kg/day (trough 6-10 ng/ml first 6M and 4-6 ng/ml for next 3M) then both taper by 1/3 every month up to 12M. Out of 101 patients, 15 diabetic, 7 lupus, 1HBV and 1 ankylosing spondylitis patients were excluded. Finally, 77 Patients were followed and evaluated for the anti-PLA2R level at baseline, 3M, 6M,12M and end of follow-up (17-61 , median 38 months). CR, PR, relapse, and side-effects were recorded. Of the 77 patients, at 3M 60(77.92%; CR-37, PR-23); at 6M 61(79.22%; CR-53, PR-8); at 12M 53(68.86%; CR-47, PR-6) achieved remission. Eight (10.38%) relapsed and 16(20.77%) showed no response at 12M. At end of follow-up, out of 54 responsive patients 37(68.51%; CR-36, PR-1) remained in remission and 17(31.48%) patients relapsed. Out of 77 patients, 51 (66.3%) were anti-PLA2R positive. Remission rate was significantly low in PLA2R+ve than PLA2R-ve (36/51 vs 24/26; p=0.03) at 3M, (36/51 vs 25/26; p=0.009) at 6M and (31/51 vs 22/26; p=0.03) at 12M. PLA2R level was decreased by 60.38% and 77.56% at 3M and 6M respectively. There were significant correlations between PLA2R level and 24h proteinuria at baseline, 3M and at 6M. (Figure-1) During therapy 4 patients develop cutaneous tenia, 1 osteonecrosis of the femur head, 1 corpus tunnel syndrome, 4 onset diabetes, 3 tremor, and 14 patients experienced GI symptoms. The eGFR was decreased significantly (p=0.003) by 26.5% at the end of therapy and was normalized after stopping Tac, and 5 non-responsive patients had doubling of serum creatinine and progressively deteriorated eGFR. To note, 4 females had pregnancy and successful delivery in our cohort of patients. PLA2R+ve patients showed poor response compare to PLA2R-ve patients. Remission with Tacrolimus and prednisolone therapy is comparable to historical Ponticelli (Pred plus CYP) regimen. Successful pregnency was ovserved on Tac based regimen.

Serum phospholipase A2 receptor antibodies and immunoglobulin G subtypes in adult idiopathic membranous nephropathy: Clinical value assessment

BackgroundIdiopathic membranous nephropathy (IMN) is widely considered as an organ-specific autoimmune disorder. Implicated in its pathogenesis are the phospholipase A2 receptors (PLA2R) expressed on glomerular podocytes against which serum antibodies are formed. In this study we quantified and assessed the clinical value of total serum PLA2R antibodies and the subtype antibodies in IMN. MethodsWe measured serum levels of total PLA2R antibodies and IgG subtype antibodies by Enzyme Linked Immunosorbent Assay (ELISA) in 146 biopsy-proven IMN patients, 51 non-IMN patients and 62 healthy controls. We went ahead and determined the diagnostic potential of total serum PLA2R antibodies and assessed if a relationship exists between the dominat subtype antibody and the clinical parameters. ResultsThe diagnostic sensitivity and specificity of total serum PLA2R antibody for IMN were found at 69.9% and 100% respectively. Significant differences in systolic blood pressure, serum Cystatin C, serum albumin and estimated glomerular filtration rate (eGFR) were found between the antibody-positive and antibody-negative groups of IMN patients. Subtype antibody 4 and 1 exhibited the highest positive rates of 94.4% and 91.6% respectively. The mean serum proportion of subtype antibodies was 65.4, 12.7, 7.6 and 4.6% for subtype 4, 1, 3 and 2 respectively. Serum levels of total protein and albumin were significantly decreased among patients with high serum titres of antibody subtype 4. ConclusionOur findings underscore the diagnostic potential of total serum PLA2R antibodies and highlight the importance of antibody subtype 4 over other subtype antibodies in IMN.

The Release of Monocyte-Derived Tissue Factor-Positive Microparticles Contributes to a Hypercoagulable State in Idiopathic Membranous Nephropathy.

Aim: Idiopathic membranous nephropathy (IMN) is an immune-mediated inflammatory disease characterized by a high risk of thromboembolic complications. Microparticles (MPs), a type of extracellular vesicles, have procoagulant properties, especially when they display tissue factor (TF). This study aimed to investigate whether circulating TF-positive MPs contributed to the hypercoagulable state in patients with IMN.Methods: Twenty adult IMN patients and fourteen healthy subjects were included in the study. The basic indexes of a routine biochemical examination and coagulative function were determined. The plasma levels of MPs were detected by flow cytometry, and TF activity of MPs was examined using an assay kit. The plasma levels of lipopolysaccharide (LPS) were measured by an enzyme-linked immunosorbent assay.Results: Total circulating MPs were not increased in patients with IMN compared with healthy controls. Circulating CD14+/TF+MPs were significantly increased in IMN patients, but this achieved significance was not observed in CD41+/TF+MPs between the two groups. Interestingly, the circulating TF-positive MPs were increased significantly. Plasma MPs TF assays revealed high procoagulant activity, which was positively associated with the D-dimer level in IMN. In addition, circulating LPS in IMN patients were significantly higher than those in the controls. Furthermore, after two hours' incubation with healthy whole blood, LPS enhanced the release of circulating TF-positive MPs and the TF activity of MPs.Conclusion: Increased circulating LPS may mediate the release of monocyte-derived TF-positive MPs, which further contributes to the hypercoagulable state in IMN patients. These findings provide an additional mechanism by which patients with IMN have a higher risk of thromboembolic complication.

M-type phospholipase A2 receptor (PLA2R) glomerular staining in pediatric idiopathic membranous nephropathy.

Identifying M-type phospholipase A2 receptor (PLA2R) is a landmark breakthrough for understanding adult idiopathic membranous nephropathy (iMN). However, potential roles for PLA2R in pediatric iMN have not been well investigated. A total of 34 pediatric iMN patients who underwent kidney biopsy between 1972 and 2015 were enrolled in this study. The study cohort consisted of 15 children aged from 3 to 9years and 19 aged from 10 to 15years. In all cases, secondary causes of MN, including infections, autoimmune diseases, and others, were ruled out. We examined PLA2R glomerular staining in stored, formalin-fixed, paraffin-embedded kidney biopsy samples. Kidney biopsy specimens obtained from an adult patient with iMN and an adult patient with lupus-associated MN were also examined to assess our PLA2R staining procedure. Granular staining of PLA2R along glomerular capillary loops was present in two patients: an 11-year-old girl and 12-year-old boy identified during a school urine screening test and who presented with mild proteinuria at the time of biopsy. Interestingly, the intensity of PLA2R glomerular staining in these patients was weaker than that of a PLA2R-positive adult iMN patient. There were no PLA2R-positive patients among our cohort of children younger than 10years. This preliminary study suggests PLA2R may play a role in some adolescent and preteen iMN patients but may be less frequently associated with iMN during childhood.

Antibodies to m-type phospholipase A2 receptor in children with idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (IMN), the commonest cause of adult nephrotic syndrome (NS), accounts for only a minority of paediatric NS. Antibodies to m-type phospholipase A2 receptor (PLA2R) are seen in two-thirds of adult IMN cases. PLA2R staining in glomerular deposits is observed in 74% and 45% of adult and paediatric IMN cases, respectively. However, there are no reports of anti-PLA2R in paediatric IMN. We evaluated anti-PLA2R levels and PLA2R in gloemrular deposits in paediatric IMN seen at our center. Five cases were enrolled, all the cases stained for PLA2R in glomeruli and three (60%) had antibodies to PLA2R antigen. There was a parellel reduction in proteinuria and anti-PLA2R titer. The present report suggests that PLA2R has a contributory role in the pathogenesis of paediatric IMN.

Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome.

Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome.

Meta-Analysis of Association between Pathological Characteristics and Renal Outcomes in Adult Idiopathic Membranous Nephropathy

Background and objectives: The associations of pathological features with renal outcomes in adult Idiopathic Membranous Nephropathy (IMN) are still controversial. A meta-analysis was performed to assess whether pathological features could independently predict risk of progressive kidney disease in adult IMN patients. Methods: The PubMed database (January 2000 to September 2013) was searched to identify cohort studies of adult IMN patients (≥ 50 patients for each study) in which at least one of the following pathological features was assessed: segmental sclerosis, tubular atrophy/interstitial fibrosis, arteriosclerosis, C3 deposits by immunofluorescence, and the stage or heterogeneity of electron dense deposits by electron microscopy. Renal outcomes included development of renal insufficiency or progression to ESRD. Results: Nine cohort studies were included. A total of 2080 patients with 252 hard endpoints (renal insufficiency or ESRD) were reported. Segmental sclerosis was significantly associated with poor renal outcomes (8 studies with 1622 patients: hazard ratio, 1.59 [95% confidence interval, 1.07-2.37], P=0.02). Tubular atrophy/interstitial fibrosis and arteriosclerosis were also significantly associated with poor renal outcomes (7 studies with 1569 patients: 3.85 [2.16-6.87], P<0.000001; and 5 studies with 1349 patients: 1.83 [1.17-2.86], P=0.008). There were insufficient data to systematically assess the independent predictive value of C3 deposits and the stage and heterogeneity of electron dense deposits. Conclusions: Significant associations of renal outcomes with segmental sclerosis, chronic tubule interstitial injury, and arteriosclerosis were only confirmed in two, five, and one of nine included studies, respectively. However, this meta-analysis indicated that each of these pathological features was significantly associated with progression of kidney disease. More methodologically sound and sufficiently powered prospective cohort studies with adequate number of patients and length of follow-up are still urgently needed to address the questions regarding prognostic utility of pathological features in adult IMN patients.

Immunosuppression for Membranous Nephropathy

The efficacy and safety of immunosuppression for idiopathic membranous nephropathy (IMN) with nephrotic syndrome are still controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed. The Cochrane Library, PUBMED, EMBASE, Chinese Database, and Clinical Trial Registries (June 2012) were searched to identify RCTs investigating the effect of immunosuppression on adults with IMN and nephrotic syndrome. This review was an update (36 RCTs, 1762 participants) of the 2004 version (18 RCTs, 1025 participants). Immunosuppression significantly reduced all-cause mortality or ESRD (15 RCTs, 791 participants; risk ratio, 0.58 [95% confidence interval, 0.36-0.95]; P=0.03). However, the result was not consistent when prespecified subgroup analyses were undertaken. Immunosuppression increased complete or partial remission (CR + PR) (16 RCTs, 864 participants; 1.31 [1.01-1.70]; P=0.04) but resulted in more withdrawals or hospitalizations (16 RCTs, 880 participants; 5.35 [2.19-13.02]; P=0.002). Corticosteroids combined with alkylating agents significantly reduced all-cause mortality or ESRD (8 RCTs, 448 participants; 0.44 [0.26-0.75]; P=0.002) and increased CR + PR (7 RCTs, 422 participants; 1.46 [1.13-1.89]; P=0.004) but led to more adverse events (4 RCTs, 303 participants; 4.20 [1.15-15.32]; P=0.03). Cyclophosphamide was safer than chlorambucil (3 RCTs, 147 participants; 0.48 [0.26-0.90]; P=0.02). Cyclosporine and mycophenolate mofetil failed to show superiority over alkylating agents. Tacrolimus and adrenocorticotropic hormone significantly reduced proteinuria. Alkylating agents plus corticosteroids had long-term and short-term benefits for adult IMN, but resulted in more withdrawals or hospitalizations.

Glomérulopathies extramembraneuses idiopathiques et secondaires

Antibodies to neutral endopeptidase, a podocyte protein, are responsible for rare alloimmune neonatal membranous nephropathy that develops in children from neutral endopeptidase-deficient mothers. Neutral endopeptidase was the first podocyte antigen described in human membranous nephropathy. PLA2R1, the type-M receptor of soluble phospholipase A2, is a major target antigen in so-called idiopathic membranous nephropathy in adults. Antibodies to PLA2R1 are detected in 60 to 80% of patients before immunosuppressive treatment, and are only occasionally found in secondary membranous nephropathy. To date, they have not been detected in other pathological conditions and in healthy individuals. PLA2R1 and HLA-DQA1 gene variants defined by single nucleotide polymorphisms are strongly associated with idiopathic membranous nephropathy in patients of white ancestry, and can thus be considered as predisposing genes. In addition to their diagnostic value, anti-PLA2R1 antibodies can be used to monitor treatment. Immunization against cationic bovine serum albumin is a cause of early childhood membranous nephropathy. This finding points to a possible role of food and environmental antigens in membranous nephropathy. The newly identified antigen-antibody systems should be considered as molecular signatures challenging the uniform histological definition and having a major impact on patient care in a near future.