Idiopathic Membranous Nephropathy Group Research Articles

Idiopathic membranous nephropathy with focal segmental sclerosis

Aim. To evaluate the clinical and pathological features and prognosis of idiopathic membranous nephropathy (IMN) with focal segmental sclerosis (FSGS) in a group of Russian patients. Materials and methods. 101 patients with morphologically verified IMN were enrolled in our single-center cohort retrospective study. The patients were divided into IMN group and IMN+FSGS group. The primary and secondary outcomes were analyzed in 59 patients, which had follow-up data for period more than 6 months. Results. At the time of renal biopsy the median age was 46.0 (33.0; 55.0) years and the median follow-up was 6.8 (4.0; 15.6) months. Secondary FSGS was revealed in 15 (14.9%) patients with IMN. The IMN and IMN+FSGS groups did not differ in gender, age of onset IMN and age of renal biopsy. In the IMN+FSGS group proteinuria was higher and estimated glomerular filtration rate was lower than that in the IMN group (p0.05). The systolic arterial pressure and creatinine levels in the IMN+FSGS group were slightly higher than in the IMN group, but the difference was not significant. Anti-PLA2R positivity was similar in both groups. Chronic kidney disease (CKD) progression was observed in 10/52 (19.2%) and 5/7 (71.4%) patients in IMN and IMN+FSGS groups, respectively. In a multivariate Cox regression model, age of renal biopsy (odds ratio – OR 1.12, 95% confidence interval – CI 1.03–1.22; р=0.07), FSGS (OR 0.05, 95% CI 0.01–0.34; р=0.002) и response to initial course of immunosuppression (OR 0.33, 95% CI 0.12–0.95; р=0.039) were associated with the CKD progression. Conclusion. In patients with IMN secondary FSGS is associated with a greater severity of proteinuria and a decrease in estimated glomerular filtration rate, and is also an independent factor of the CKD progression.

Serum anti-phospholipase A2 receptor antibody in pathological diagnosis of type 2 diabetes mellitus patients with proteinuria

Patients with diabetes mellitus complicated with proteinuria can be diabetic nephropathy (DN), diabetic complicated with non-diabetic kidney disease (NDKD), or DN with NDKD. Among these membranous nephropathy accounted for a large proportion of DN with NDRD. At present, serum anti-phospholipase A2 receptor (PLA2R) antibody is widely used in the diagnosis and evaluation of therapy in idiopathic membranous nephropathy, our study aimed to investigate the diagnostic significance of anti-PLA2R antibody in type 2 diabetes mellitus (T2DM) patients with proteinuria, providing a method for patients with contraindications of kidney biopsy. Eighty-seven T2DM patients with proteinuria who went on kidney biopsy were divided into the DN group, idiopathic membranous nephropathy (IMN) group, and others group according to their pathological results. In our study, 52.87% and 28.74% of patients were found to have IMN and diabetic nephropathy respectively. The levels of anti-PLA2R antibody, total cholesterol, triglyceride, and estimated glomerular filtration rate (eGFR) were higher in the IMN group, while the prevalence of diabetic retinopathy (DR), systolic blood pressure (SBP) and HbA1c were higher in the DN group. For T2DM patients with proteinuria, anti-PLA2R antibody (AUC = 0.904, 95%CI 0.838–0.970) has a high diagnostic value for IMN. The duration of diabetes (OR = 0.798, P = 0.030), eGFR level (OR = 1.030, P = 0.024), and positive anti-PLA2R antibody (OR = 72.727, P < 0.001) favor the diagnosis of IMN, while DR (OR = 50.234, P < 0.001), SBP (OR = 1.041, P = 0.030), and negative anti-PLA2R antibody (OR = 0.008, P = 0.001) is beneficial to the diagnosis of DN. Our study found that NDKD is not uncommon in patients with T2DM and proteinuria, and IMN was the main pathological type. Positive anti-PLA2R antibody has a strong accuracy in the diagnosis of IMN in patients with T2DM and proteinuria.

The cutoff value and prognosis of anti-PLA2R antibody for idiopathic membranous nephropathy: a single-center retrospective study in China

Serum anti-phospholipase A2 receptor (anti-PLA2R) antibody is used for the noninvasive diagnosis of idiopathic membranous nephropathy (IMN). However, the cutoff value of anti-PLA2R antibodies in IMN patients is debatable. This study aimed to investigate the cutoff value of anti-PLA2R antibodies for diagnosing IMN and the correlation of anti-PLA2R antibodies with clinical parameters and prognosis. A total of 252 IMN patients and 521 non-IMN patients with both renal biopsy and serum anti-PLA2R antibody data from April 2017 to November 2019 were enrolled. Anti-PLA2R antibody was detected by an enzyme-linked immunosorbent assay. The anti-PLA2R antibody titer was higher in the IMN group than in the non-IMN group (153.1 ± 22.4 vs. 2.0 ± 0.2 RU/mL, p < 0.001). The optimal anti-PLA2R antibody cutoff value for diagnosing IMN was 2.5 RU/mL, with a sensitivity, specificity, and Youden index of 85.7%, 88.3%, and 0.740, respectively. There was a significant positive correlation between anti-PLA2R antibody and 24-h urinary protein levels (r = 0.341, p < 0.001), and a significant negative correlation between anti-PLA2R antibody and serum albumin levels (r=−0.274, p < 0.001) in patients with IMN. The remission rates positively correlated with the immunosuppressive usage rates and increased from the low- to the high-titer subgroup. Multivariable Cox regression analysis showed that immunosuppressive therapy (adjusted HR = 4.656; 95% confidence interval [CI], 1.461–14.839; p = 0.009) was associated with a higher remission rate in patients with IMN. The optimal Anti-PLA2R antibody cutoff value for diagnosing IMN was 2.5 RU/mL, which was much lower than that indicated by the manufacturer. If IMN is actively treated, patients can have much better prognoses. Trial registration: retrospectively registered.

Single-cell RNA sequencing shows the immune cell landscape in the kidneys of patients with idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (IMN) is a leading pathological type of the adult primary nephrotic syndrome. Some patients develop end-stage renal disease due to poor response to treatment with steroid and immunosuppressive agents. In order to explore the molecular mechanism of IMN, we collected renal tissue samples from IMN patients and healthy controls and performed analysis by single-cell RNA sequencing (scRNA-seq). A total of 11 kidney cell clusters were identified, including multiple myeloid cell clusters, NK/T cell clusters, and B cell clusters. Most kidney parenchymal and immune cells were enriched in the regulation of immune response, inflammation, fibrosis and endoplasmic reticulum stress. The macrophage population in the IMN group showed a highly activated profile with up-regulated genes related to chemotaxis, inflammation, phagocytosis and fibrosis. CD8+ T cells continued to be cytotoxic in IMN; however, a transition to "inflammageing" GZMK+ CD8+ T cells was observed. The proportion of activated B cells in renal tissues of IMN patients was much higher than that of normal controls, indicating that B cells in IMN might be activated by constant antigenic stimulation. Moreover, the cell-cell interaction analysis revealed the potential communication between renal glomerular cells and immune cells in IMN. Overall, scRNA-seq was applied to IMN to unravel the characteristics of immune cells and elucidate possible underlying mechanisms involved in the pathogenesis of IMN.

Anti-phospholipase A2 Receptor Antibody Measurement in Patients with Idiopathic Membranous Nephropathy Diagnosed by Renal Biopsy

Objective: Our study is a cross-sectional study that aims to evaluate the presence and levels of anti-phospholipase A2 receptor (PLA2R) antibodies in healthy volunteers and idiopathic membranous nephropathy (IMN) patients and to assess the relationship between these levels and clinical parameters. Methods: Serum anti-PLA2R antibody levels, complete blood count, urea, creatinine (Kre), total protein,albumin, low-density lipoprotein (LDL)-cholesterol, triglycerides (TG), high-density lipoprotein (HDL)-cholesterol, total cholesterol, C-reactive protein (crp), sedimentation, proteinuria were measured from 71 IMN patients and 48 healthy volunteers. Results: Of the values compared between the two groups, the urea, creatinine, and modified diet renal disease (MDRD) were similar, total protein, albumin, LDL-cholesterol, TG, total cholesterol, HDL-cholesterol, and complete urinalysis protein values were statistically significantly high in the patient group, as expected in nephrotic syndrome (p&lt;0.01). The anti-PLA2Rantibody levels measured using enzyme-linked immunosorbent assay (ELISA) in patient and control groups were found to be negative. The anti-PLA2R level was found to be 0.104 (0.093-0.129) ng/ml in the IMN group, while it was 0.141 (0.117-0.177) ng/ml in the control group (P=0,001). Although the P value was significant, the anti-PLA2R antibody level was found to be high in the control group and was outside the reference range of the kit. Conclusion: There is a need to conduct more sensitive studies with a higher number of patients in order to distinguish between primary and secondary nature and to investigate the presence of anti-PLA2R in IMNpatients, which constitute the majority of nephrotic syndromes in adults. Antibody titer levels were observed to be low and it was revealed that the measurement range of the antibody kit used in the study should be more sensitive.

The Safety and Efficacy of Rituximab-Based Regimen in Atypical Membranous Nephropathy: A Single Center Retrospective Cohort Study.

There are increasing reports of atypical membranous nephropathy (AMN) cases with similar pathological characteristics to secondary membranous nephropathy (SMN) without definite underlying causes. Although rituximab has become a first-line option in treating idiopathic membranous nephropathy (IMN), the efficacy and safety of rituximab-based regimen for AMN is not clear. This is a retrospective, single-center study. AMN patients who received rituximab-based therapy were included. IMN patients treated with rituximab during the same period were selected as the control group matched by gender, sex, baseline urinary protein and albumin levels. Baseline data and follow-up data were collected. A total of 20 AMN patients and 40 IMN patients were included. The baseline levels of urinary protein were comparable between the two groups [6.77 (IQR 3.34, 11.49) g/24 h vs 6.47 (IQR 3.4, 10.76) g/24 h, P=0.944]. The baseline levels of serum albumin were 26.15±6.71 g/L and 26.8±5.54 g/L (P=0.689) respectively. The cumulative remission rate for rituximab-based treatment at the 12th month was lower in AMN group than IMN group [13 (65%) vs 36 (90%), P=0.045]. In AMN group, non-responders showed a higher level of proteinuria and a worse renal function at baseline than those of responders. There was no significant difference in the overall adverse events or serious adverse events between the two groups. In our study, AMN patients obtained proteinuria remission in a lower percentage compared with IMN patients. In general, rituximab-based therapy is effective in AMN patients with an acceptable safety profile.

Association between PLA2R gene polymorphism and idiopathic membranous nephropathy in Heilongjiang Chinese.

The aim of this study was to investigate the correlation between the phospholipase A2 receptor (PLA2R) gene polymorphism and idiopathic membranous nephropathy (IMN) in Heilongjiang Chinese. Thirty-five patients with IMN confirmed by renal biopsy attending the Heilongjiang Hospital of Traditional Chinese Medicine between June 2021 and December of 2021 were selected as the IMN group, and a group of 25 healthy participants from the Physical Examination Center of Heilongjiang Hospital of Traditional Chinese Medicine were enrolled as healthy controls. Polymerase chain reaction (PCR) was used to identify and genotype 8 single-nucleotide polymorphism (SNP) loci (rs16844715, rs2715918, rs2715928, rs35771982, rs3749119, rs3828323, rs4665143, and rs6757188) of PLA2R and to analyze the PLA2R gene polymorphisms that correlated with IMN. SPSS 26.0 statistical software was used for data analysis, and the chi-squared (χ2) goodness-of-fit test was used to determine whether each SNP genotype and allele in the PLA2R gene complied with the Hardy-Weinberg equilibrium. The qualitative data were analyzed via χ2 or Fisher exact probability method. Logistic regression was used to analyze risk factors, and the odds ratios (ORs) values and 95% confidence intervals (CIs) were calculated. α=0.05 was taken as the test level, and P<0.05 was considered statistically significant. Statistically significant differences were found in the genotype and allele frequencies of rs35771982 and rs3749119 between the IMN and control groups (P<0.05). Logistic regression analysis showed that the genotypes rs35771982 GG and rs3749119 CC were associated with IMN susceptibility. Statistically significant differences in uric acid level were found between the rs35771982 GG and CG + CC genotypes (P<0.05), while statistically significant differences in serum albumin were detected between rs3749119 CC and the CT + TT genotypes (P<0.05). Multivariate logistic regression analysis showed that gender, age, and triglyceride levels affected the occurrence of IMN (P<0.05). The PLA2R gene polymorphisms rs35771982 and rs3749119 in Heilongjiang Chinese may be related to IMN susceptibility and correlated with clinical indicators of IMN. Gender, age, and triglyceride levels may influence the occurrence of IMN.

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

ObjectiveTo assess the significance of focal segmental glomerulosclerosis (FSGS) variants on clinicopathological characteristics and short-term outcomes in idiopathic membranous nephropathy (IMN) patients.MethodsThe 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.ResultsThe 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.ConclusionThe non-GTL FSGS lesion was a novel negative predictor in IMN and should be taken into account in the management of IMN.

GDF-15 and sST-2 act as biomarkers of disease severity but not independent predictors in idiopathic membranous nephropathy

BackgroundWe aimed to explore biomarkers of disease severity in idiopathic membranous nephropathy (IMN) and independent predictors of prognosis in IMN. MethodsClinical data were collected from 79 IMN patients. Serum levels of growth differentiation factor-15 (GDF-15) and soluble suppression of tumorigenicity (sST-2) were tested by enzyme-linked immunosorbent assay (ELISA) in IMN patients and subgroups, and correlation analysis was performed. Univariate and multiple logistic regression analyses were performed to identify independent predictors of IMN, and a combined-factors model was constructed. Moreover, the area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the prognostic efficacy. ResultsThe levels of GDF-15 were significantly higher in the IMN group and subgroups with low estimated glomerular filtration rate (eGFR) and high 24 hour-urine protein (24 h-UP), whiles sST-2 level was only significantly higher in the IMN group. GDF-15 levels were positively correlated with creatinine (Crea), cystatin C (Cys-C) and 24 h-UP and negatively correlated with GFR and albumin (Alb), while sST-2 levels were positively correlated with Urea and Cys-C and negatively correlated with eGFR. After one year of follow-up, 54 patients had incomplete remission. Serum phospholipase A2 receptor antibody (PLA2R-Ab), Urea, high-density lipoprotein cholesterol (HDL-C) and 24 h-UP but not GDF-15 and sST2 were independent predictors of prognosis in IMN patients, but combined factors showed the best prognostic efficacy. ConclusionSerum levels of GDF-15 and sST-2 may be potential biomarkers for the severity of IMN, while the combined-factors model is effective for predicting the risk factors of incomplete remission in IMN.

Association of gut microbiota with idiopathic membranous nephropathy

BackgroundThe prevalence of idiopathic membranous nephropathy (IMN) is increasing worldwide and the gut microbiota is recognized to play a role in its pathology. The aim of this study was to understand the involvement of the gut–kidney axis in IMN by analyzing the composition of the gut microbiota of biopsy-proven IMN patients compared with healthy controls (HC).MethodsFecal samples from 30 patients with IMN diagnosed by renal biopsy and 30 healthy co-residents (control group) were collected for analysis in the Nephrology Department of the Second Affiliated Hospital of Harbin Medical University. The microbiota composition was analyzed by a 16S rRNA microbial profiling approach.ResultsThe results indicated that the α- and β-diversity of IMN patients differed significantly from those of the HC groups (P < 0.05). At the phylum level, IMN patients showed an increased abundance of Proteobacteria but a reduced abundance of Bacteroidota compared with the HC group. Actinobacteriota abundance showed a strong negative correlation with the estimated glomerular filtration rate. At the genus level, Faecalibacterium, Agathobacter, and Bacteroides were less abundant in the IMN group than in the HC group (LDA score > 2). Abundant bacterial functions related to lipid metabolism were observed among IMN group.ConclusionPatients with IMN appear to have an altered gut microbiome, which could provide reference for future research on the interaction mechanism between the intestinal flora and IMN.

Clinicopathological characteristics and prognosis of hepatitis B associated membranous nephropathy and idiopathic membranous nephropathy complicated with hepatitis B virus infection

The main objective of this study is to analyze the clinical and pathological features and prognosis of patients with Hepatitis B associated membranous nephropathy (HBV-MN) and idiopathic membranous nephropathy (IMN) complicated with hepatitis B virus (HBV) infection. This study will provide more basis for diagnosis and prognosis evaluation. A total of 50 patients with HBV-MN were included in this study. 56 IMN patients complicated with HBV infection diagnosed during the same period formed the control group. Parameters including blood routine, urine routine and plasma levels of albumin (ALB), serum creatinine (SCR), blood urea nitrogen (BUN), urea acid (UA), total cholesterol (T-CHO), triglycerides (TG), complement C3 and C4, glutamic pyruvic transaminase (ALT), glutamic pyruvic transaminase (AST), 24-h urinary protein quantification (24 h-TP), renal phospholipase A2 receptor (PLA2R) and HBV related markers during the hospitalization and outpatient follow-up study period were collected for all the patients. The proportion of male patients was high in both groups. The average age of the HBV-MN group was 37.2 ± 14.187 years old, it was younger compared with the IMN group (P = 0.003). Nephrotic syndrome was the major clinical manifestation among patients. There was no significant difference between the two groups in the levels of anemia, microscopic hematuria, renal dysfunction, liver dysfunction, liver cirrhosis. The level of serum C3 and C4 in the HBV-MN group was lower compared with the IMN group (P = 0.002, P = 0.014). In the HBV-MN group, serum HBV markers were negative in 6 (12%) patients, 4 patients (8%) were positive for PLA2R in serum, and 5 patients (10%) were positive for PLA2R in renal tissue. Stronger IgG1 and C1q and weaker IgG4 staining were found in HBV-MN group renal tissues (P = 0.003, P = 0.025, and P = 0.001, respectively). There were no statistical differences compared with serum and renal PLA2R between HBV-MN and IMN groups (P = 0.098, P = 0.109). During the 1-year follow-up, there was no significant difference in complete remission rate between the two groups (P = 0.7739). Renal biopsy is crucial to diagnose HBV-MN. IgG subtypes in the HBV-MN group were mainly IgG1 deposition, while those in IMN complicated with HBV infection group were mainly IgG4 deposition. When HBV-associated antigen and PLA2R are present in renal tissue, lower level of serum C3 and C4, high intensity of renal C1q and IgG1 is more supportive of HBV-MN. The positive of PLA2R in serum and renal tissue in differentiating HBV from IMN complicated with HBV infection remains to be discussed.

Kidney transplantation outcomes in patients with IgA nephropathy and other glomerular and non-glomerular primary diseases in the new era of immunosuppression.

ObjectivesKidney transplant (KTx) recipients with IgAN as primary disease, were compared with recipients with other causes of renal failure, in terms of long-term outcomes.MethodsNinety-nine KTx recipients with end-stage kidney disease (ESKD) due to IgAN, were retrospectively compared to; i/ a matched case-control group of patients with non-glomerular causes of ESKD, and ii/ four control groups with ESKD due to glomerular diseases; 44 patients with primary focal segmental glomerulosclerosis (FSGS), 19 with idiopathic membranous nephropathy (IMN), 22 with lupus nephritis (LN) and 21 with pauci-immune glomerulonephritis (PIGN).ResultsAt end of the observation period, graft function and survival, were similar between KTx recipients with IgAN and all other groups, but the rate of disease recurrence in the graft differed significantly across groups. The rate of IgAN recurrence in the graft was 23.2%, compared to 59.1% (p<0.0001) in the FSGS group, 42.1% (p = 0.17) in the IMN group, and 0% in the LN and PIGN groups (p = 0.01). IgAN recipients, who were maintained with a regimen containing tacrolimus, experienced recurrence less frequently, compared to those maintained with cyclosporine (p = 0.01). Graft loss attributed to recurrence was significantly higher in patients with FSGS versus all others.ConclusionRecipients with IgAN as primary disease, experienced outcomes comparable to those of recipients with other causes of ESKD. The rate of IgAN recurrence in the graft was significantly lower than the rate of FSGS recurrence, but higher than the one recorded in recipients with LN or PIGN. Tacrolimus, as part of the KTx maintenance therapy, was associated with lower rates of IgAN recurrence in the graft, compared to the rate cyclosporine.

The correlation between polycyclic aromatic hydrocarbons and idiopathic membranous nephropathy

Objective: To explore the relationship between polycyclic aromatic hydrocarbons (PAHs), the major component of atmospheric pollutant particulate matter 2.5 (PM2.5) and idiopathic membranous nephropathy (IMN) and its possible mechanisms. Methods: Thirty-five (24 males and 11 females) patients with IMN confirmed by renal biopsy pathology in the First Affiliated Hospital of Zhengzhou University from June to September 2020 were selected as the research group, with an age of (47.3±12.9) years. Meanwhile, patients with secondary membranous nephropathy (SMN, n=10) and minimal-change disease (MCD, n=10) were selected as control group. Blood samples were collected to detect PAHs and heme oxygenase-1 (HO-1), and the relationship of PAHs with clinical indicators and oxidative stress indicator HO-1 was analyzed. Results: Compared with SMN and MCD groups [(2.6±1.7) mg/L and (2.8±1.0) mg/L], the concentration of PAHs in IMN group [(4.1±1.9) mg/L] increased (both P<0.05). The concentration of PAHs was positively correlated with the levels of β2 microglobulin, total cholesterol and 24-hour urine total protein (r=0.509, 0.336, and 0.653, respectively, all P<0.05), but was negatively correlated with the levels of total protein and albumin (r=-0.499,-0.530, respectively, both P<0.05). Additionally, the concentration of PAHs was negatively correlated with the level of HO-1 (r=-0.358, P=0.017). Linear regression analysis showed that the concentration of HO-1 decreased by 1.737 μg/L when the concentration of PAHs increased by 1 mg/L (P=0.035). Conclusion: PAHs have a high level in IMN patients, and may be involved in the occurrence and development of IMN through oxidative stress.

Altered expression of serum miR-106a, miR-19b, miR-17, and PTEN in patients with idiopathic membranous nephropathy.

BackgroundTo find new diagnostic markers for idiopathic membranous nephropathy (IMN) and also conduct preliminary explorations into the possible pathogenesis of IMN by comparing the expression of microRNA‐451a (miR‐451a), miR‐106a, miR‐19b, miR‐17, and phosphatase and tensin homolog (PTEN) protein in the serum of patients with IMN and healthy controls.MethodsThe expression levels of miR‐451a, miR‐106a, miR‐19b, and miR‐17 in the serum of patients in the IMN group (n = 55, age: 50.2 ± 12.1 years) and the control group (n = 58, age 47.4 ± 13.1 years) were measured by quantitative real‐time polymerase chain reaction (qRT‐PCR), and the concentration of serum PTEN protein was determined by enzyme‐linked immunosorbent assay (ELISA).ResultsCompared with the control group, the expression of miR‐106a, miR‐19b, and miR‐17 was decreased significantly in the IMN group, whereas PTEN protein concentration was increased significantly in the IMN group. The areas under the receiver operating characteristic curve (AUC) of serum miR‐106a, miR‐19b, miR‐17, and PTEN were 0.66 (95% confidence interval [CI], 0.56–0.76), 0.81 (95% CI, 0.73–0.89), 0.69 (95% CI, 0.59–0.79), and 0.86 (95% CI, 0.79–0.93), respectively. The level of serum PTEN protein was negatively correlated with the expression of miR‐106a and miR‐19b. PTEN concentration was positively correlated with serum urea (Urea), creatinine (Crea), cystatin C (Cysc), 24 h urine total protein (24 h‐UP) and negatively correlated with albumin (Alb) and estimated glomerular filtration rate (eGFR).ConclusionsMiR‐106a, miR‐19b, miR‐17, and PTEN are involved in the pathogenesis of IMN and may become new biomarkers for the diagnosis of IMN.

The role of adiponectin and its receptor in patients with idiopathic membranous nephropathy complicated with hyperuricemia

Introduction/Objective. This study aimed to assess the changes of adiponectin (APN), IL-1?, adiponectin receptor 1 (Adipo R1), and NLRP3 expression of patients with idiopathic membranous nephropathy (IMN) complicated with hyperuricemia (HUA) and analyze the relationship between the APN pathway and the NLRP3 pathway. Methods. A group of 48 patients with IMN + HUA, a group of 49 patients with IMN, 30 healthy controls, and 24 samples of healthy renal tissue were evaluated. APN and IL-1? of each group were detected by the ELISA method. AdipoR1 and NLRP3 in kidney tissue were detected by immunohistochemistry. The clinical data of each group were collected, and the relationship between APN, IL-1?, AdipoR1, NLRP3, and other indexes was analyzed. Results. (1) The concentration of UA, APN, IL-1?, and NLRP3 in the IMN + HUA group were significantly higher than those in the IMN group, but the AdipoR1 was lower. (2) With the severity of chronic kidney disease stage, APN, IL-1?, and NLRP3 gradually increased in the IMN + HUA group, but AdipoR1 gradually decreased. However, the aforementioned indicators did not change significantly in the IMN stages. Conclusion. The AdipoR1?AMPK and NLRP3?caspase-1?IL-1? signaling pathway may play an essential role in IMN + HUA patients. An intervention on these two pathways may have significant impact on the disease occurrence and progression in IMN + HUA patients.

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

BackgroundThe incidence of idiopathic membranous 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). MethodsAmong 40 patients 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. ResultsBaseline characteristics did not significantly 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 ± 9.14 g/L, P > 0.05). Values for urea nitrogen, serum creatinine, and eGFR did not significantly 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. After TCM 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. ConclusionPatients with IMN might have disordered intestinal flora, and JPQSF can regulate intestinal flora in patients with IMN.

Characterization of thromboelastography of patients with different pathological types of nephrotic syndrome.

To investigate the changes in blood coagulability as measured by thromboelastography (TEG) in patients with nephrotic syndrome of different etiologies as well as in patients with venous thromboembolic events (VTE).From January 2013 to October 2017, patients who were diagnosed as idiopathic membranous nephropathy (IMN), minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) were enrolled into this retrospective study in which their clinical characteristics, including TEG variables, were investigated. According to the presence or absence of VTE, the patients with IMN were divided into 2 groups of VTE and non-VTE. The risk factors of VTE were analyzed with logistic regression.Significant differences in TEG parameters were found among the 3 groups of patients with R and K values lower, while the α-angle, maximum amplitude (MA) and confidence interval (CI) values higher, in the IMN group than those in the MCD and FSGS groups (P < .01). Multiple linear regression analysis indicated that the histologic subtype was an independent relevant factor of K time, angle, MA, and CI values. Multivariate logistic regression analysis revealed that serum albumin and CI value were independent risk factors of VTE (P < .05).The results showed that IMN patients may have higher whole blood coagulability than MCD and FSGS patients. The hypercoagulability in IMN patients may be attributed to platelet hyperactivity and the accelerated fibrin-platelet interaction. Hypoproteinemia and increased CI value were independent risk factors of VTE in IMN.

Diagnostic efficacy of serum anti-phospholipase A2 receptor antibodies for idiopathic membranous nephropathy in patients with diabetic kidney disease

AimSerum anti-phospholipase A2 receptor (anti-PLA2R) antibodies are highly accurate in diagnosing idiopathic membranous nephropathy (IMN) in populations with kidney disease. However, the diagnostic value of anti-PLA2R antibodies for IMN in diabetic kidney disease (DKD) is unclear. The objective of this study is to determine the diagnostic efficacy and the optimal cut-off value of this marker in populations with DKD. MethodsThis study included 227 patients with type 2 diabetes who were admitted to the Department of Nephrology of the Chinese People’s Liberation Army General Hospital from May 2016 to January 2018 and underwent pathological diagnosis by renal biopsy. Anti-PLA2R antibodies were detected by enzyme-linked immunosorbent assay in this population. According to the pathological results, the participants were divided into an IMN group and non-membranous nephropathy (non-MN) group. The clinical characteristics were analyzed, the diagnostic ability of anti-PLA2R antibodies was evaluated, and the receiver operating characteristic (ROC) curve was constructed to obtain the optimal cut-off value. ResultsThere were 45 patients in the IMN group, accounting for 19.8% of the study sample. The patients in this group were older at the time of renal biopsy than the non-MN group and presented a shorter duration of diabetes, better glycemic control, lower blood pressure and uric acid, and better renal function; in addition, their clinical symptoms indicated nephrotic syndrome. The optimal cut-off value for anti-PLA2R antibodies for the diagnosis of IMN in DKD was 2.71 Ru/ml, sensitivity was 0.800, specificity was 0.951, positive predictive value was 0.800, negative predictive value was 0.951, accuracy was 0.921, and the Yoden index was 0.750. The area under the ROC curve was 0.87 (95% CI, 0.788–0.952) (p < 0.001). ConclusionsPatients in the IMN group were older, had better renal function and general condition, and the clinical symptoms indicated nephrotic syndrome. Anti-PLA2R antibodies had a good diagnostic performance for IMN in the population with DKD, and the optimal cut-off value was 2.71.

Potential role of soluble TNF-α receptors in diagnosis of idiopathic membranous nephropathy

Soluble tumor necrosis factor alpha (TNF-α) receptors contain two receptors: soluble tumor necrosis factor receptor (sTNFR) 1 and 2, and the aim of our study was to discover their concentration and diagnostic value for idiopathic membranous nephropathy (IMN). In total, 58 patients with IMN, 51 patients with chronic kidney disease (CKD), and 30 healthy volunteers were enrolled in this study. Levels of serum sTNFR1 and sTNFR2 were determined by enzyme-linked immunosorbent assay (ELISA). Serum cystatin C (CysC), urea, creatinine (CREA), uric acid (UA), total protein (TP), albumin (ALB), and 24-h urinary protein (proteinuria, PRO) were examined by automatic biochemical analyzer. Levels of sTNFR1 and sTNFR2 were significantly higher in IMN group than CKD and control group ( P &lt; 0.05). In IMN group, there were significant correlation between sTNFR1 and sTNFR2 ( P &lt; 0.01). Both sTNFR1 and sTNFR2 were positively related to serum urea, CREA, CysC, UA, 24-h PRO ( P &lt; 0.05) and negatively related to ALB ( P &lt; 0.01). Receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of sTNFR1 and sTNFR2 were 0.997 and 0.993, respectively, when control was healthy volunteers. When sTNFR1 cut-off was 959.15 pg/mL, the sensitivity and specificity were 96.6% and 100%, respectively. When sTNFR2 cut-off was 2449.43 pg/mL, the sensitivity and specificity were 93.1% and 100%, respectively. While the control was CKD group, AUC of sTNFR1 and sTNFR2 were 0.647 and 0.626, respectively. When sTNFR1 cut-off was 3356.57 pg/mL, the sensitivity and specificity were 72.4% and 60.8%, respectively. When sTNFR2 cut-off was 6497.34 pg/mL, the sensitivity and specificity were 72.4% and 58.8%, respectively. This is the first study to show that both levels of sTNFR1 and sTNFR2 increased and correlated with serum urea, CREA, CysC, UA, ALB, 24-h PRO and could be usable for IMN diagnosis and differential diagnosis between IMN and CKD.

Clinicopathological Features of Idiopathic Membranous Nephropathy in 33 Adolescents.

Objective To investigate the clinicopathological features and prognosis of idiopathic membranous nephropathy(IMN)in adolescents. Methods This was a retrospective study on IMN patients hospitalized between June 2012 and December 2014,and a total of 33 IMN patients aged between 13 and 24 years old were enrolled in the study.Meanwhile,33 IMN patients aged more than 24 years old were selected randomly as control group during the same period.Diagnosis was confirmed by renal biopsy,and the secondary causes of membranous nephropathy were ruled out.Data collected from medical record and biopsy were analyzed. Results In the adolescent IMN group,the mean age at renal biopsy was(20±3)years old,and the male/female ratio was 22/11.Twenty-three cases presented as nephrotic syndrome.Systolic and diastolic pressures were(127±13)mmHg and(77±9)mmHg,respectively.The median 24-hour urine protein was 5.14(3.39,9.31)g/d,and the median serum creatinine was 62(52,73)μmol/L.The positive rate of serum anti-phospholipase A2 receptor in adolescent group was 54%.Compared with control group,the adolescent patients had lower incidence of hypertension and higher baseline estimated glomerular filtration rate level [15.2% vs.39.3%,χ2=4.889,P=0.03;125 ml/(min·1.73m2)vs.100 ml/(min·1.73m2),U=137.5,P<0.001].According to IMN staging criteria in electron microscopy,adolescent patients were classified as one case in stage I,21 in stage Ⅱ,and 11 in stage Ⅲ or higher.The positive rates of IgG1,IgG2,IgG3 and IgG4 subclass staining in glomeruli were 46.9%,3.1%,56.3%,and 87.5%,respectively.Compared with control group,the adolescent patients had lower incidence of renal interstitial fibrosis and arteriolar lesions(6.1% vs.66.7%,χ2=26.19,P<0.001;15.2% vs.66.7%,χ2=18.11,P<0.001).Three patients lost to follow-up while others started steroid combined with cyclosporine A(n=20),cyclophosphamide(n=7),or mycophenolate(n=1)or solely(n=2).After a median follow-up of 18(12,24)months,the median proteinuria decreased to 0.20(0.10,0.42)g/d,whereas serum creatinine level remained stable [69(56.8,81.3)μmol/L].Seventeen patients(56.7%)achieved complete remission(CR),and the remaining 13 patients(43.4%)achieved partial remission(PR).The median time of CR and PR were three and six months,respectively.Only one patient relapsed during the follow-up.Also,21 cases received maintenance therapy including cyclosporine A(n=18),azathioprine(n=2)and mycophenolate(n=1).Conclusions The immunofluorescence IgG subclass in glomeruli and distribution of serum anti-phospholipase A2 receptor in adolescent IMN patients are similar to those in older IMN patients.IMN patients in adolescents responded well to immunosuppressive therapy.Cyclosporine A in low dose as maintenance therapy is effective after achieving remission,and will not increase risk of nephrotoxicity.