scholarly journals Clinical Study of THSD7A, SOD2 and AR Antigens in Idiopathic Membranous Nephropathy

Author(s):  
Honggang Wang ◽  
Tingting Zhao ◽  
Jianwei Dong ◽  
Yan Zhou ◽  
Jing Huang ◽  
...  

Abstract Background To explore the expression of THSD7A, SOD2 and AR podocyte antigens in the renal tissue of patients with idiopathic membranous nephropathy (IMN) and its clinical diagnostic value in IMN. Method This study retrospectively collected 150 renal tissue specimens and clinical data of patients undergoing renal biopsy in the Department of Nephrology, Shandong Provincial Hospital, including 130 IMN and 20 non-IMN patients. We use immunohistochemical staining to detect the expression of THSD7A, SOD2, AR antigens in the kidney tissue of patients. We focus on analyzing the clinical and pathological characteristics of IMN patients with positive THSD7A antigen expression, and analyze the prognosis of THSD7A-IMN patients and tumor occurrence. Meanwhile, the sensitivity and specificity of those antigens for the diagnosis of IMN were discussed. Results There were only 6 patients with THSD7A positive expression among 150 patients with glomerular disease, of which 5 patients were all IMN patients, and the patients' serum anti-PLA2R antibodies(anti-PLA2R-ab) were all negative. The positive rate of THSD7A in IMN was 3.85%, and the positive rate in IMN patients with anti-PLA2R-ab negative was 5.50%. Meanwhile, the sensitivity and specificity of renal tissue THSD7A in diagnosing IMN is 4.0% and 95%. In addition, the IgG subtype of THSD7A-IMN was mainly IgG4; Among them, 2 patients with IMN had both THSD7A and PLA2R antigen staining. This study also suggests that there is no significant difference in clinical and pathological characteristics between THSD7A positive and negative group. The follow-up of THSD7A-IMN patients found no tumors. This study also showed that there were 11 cases of anti-PLA2R-ab negative IMN patients with SOD2 antigen expression (8.56%), 10 cases of anti-PLA2R-ab negative and 4 cases of anti-PLA2R-ab positive IMN patients with AR antigen expression (10.77%), but no obvious SOD2 and AR antigen expression in SMN and other glomerular diseases. Conclusions Glomerular THSD7A antigen has a certain expression rate and high specificity in IMN, but its expression rate is low, and it can be used as a specific diagnostic index for IMN supplement. Kidney tissue SOD2, AR podocyte target antigens have a low positive rate in IMN, and further research is needed to evaluate the condition of IMN.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ruiqiang Wang ◽  
Yunqi Wu ◽  
Bowen Zheng ◽  
Xiaofeng Zhang ◽  
Dongyue An ◽  
...  

AbstractThe 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.


2021 ◽  
pp. 31-31
Author(s):  
Tong Liu ◽  
Mengdi Xia ◽  
Yongji Zhang ◽  
Yibin Wang ◽  
Yun Zhou

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. Forty-eight patients with IMN+HUA group, 49 patients with IMN group, 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 are significantly higher than those in the IMN group, but the AdipoR1 was lower. (2) With the severity of CKD stage, APN, IL-1?, and NLRP3 gradually increased in IMN+HUA group, but AdipoR1 gradually decreased. However, the above 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. The intervention of these two pathways may make a great significance to the occurrence and progression on IMN+HUA patients.


2019 ◽  
Vol 44 (4) ◽  
pp. 848-857 ◽  
Author(s):  
Biao Huang ◽  
Yi Zhang ◽  
Liang Wang ◽  
Wenwei Xu ◽  
Jue Zhang ◽  
...  

Aims: The aim of this study was to develop a new method for detecting anti-phospholipase A2 receptor-IgG4 to improve the sensitivity and specificity in the diagnosis of idiopathic membranous nephropathy (IMN). Methods: A highly sensitive quantitative assay was developed for the detection of serum anti-phospholipase A2 receptor-IgG4 with europium chelation by time-resolved fluoroimmunoassay (TRFIA), and a mouse anti-human IgG4 tracer was prepared using europium chelation for detection. The specificity and sensitivity of anti-phospholipase A2 receptor-IgG4 in the diagnosis of IMN were further assessed in patients with different kidney diseases. Results: The detection limit of anti-PLA2R-IgG4 was 0.69 ng/mL. The measurement range of anti-PLA2R-IgG4 TRFIA was 0.69–2,500 ng/mL. Mean serum anti-PLA2R-IgG4 was 21.27 ± 15.15 ng/mL in 45 healthy volunteers, 31.08 ± 18.17 ng/mL in 29 IgA nephropathy patients, 49.10 ± 34.32 ng/mL in 8 lupus nephropathy patients, and 10,324.11 ± 17,030.40 ng/mL in 30 IMN patients. The anti-PLA2R-IgG4 cutoff concentration was >161.2 ng/mL with the sensitivity of 90.0% and specificity of 100% in the diagnosis of IMN. However, the cutoff for other kidney diseases was lower than 161.2 ng/mL. Conclusion: The serum anti-phospholipase A2 receptor IgG4 detected with the method developed in this study has higher sensitivity and higher specificity than total IgG in the diagnosis of IMN.


2018 ◽  
Vol 16 ◽  
pp. 205873921877608
Author(s):  
Chunhua Xun ◽  
Yong Zhao ◽  
Wenjuan Wang ◽  
Tiantian Cheng

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 < 0.05). In IMN group, there were significant correlation between sTNFR1 and sTNFR2 ( P < 0.01). Both sTNFR1 and sTNFR2 were positively related to serum urea, CREA, CysC, UA, 24-h PRO ( P < 0.05) and negatively related to ALB ( P < 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.


Author(s):  
Miaomiao Chen ◽  
Gaosi Xu ◽  
Xuexin Chen

Abstract Objective: This study was to evaluate the efficacy of rituximab (RTX) versus conventional agents and different RTX dose regimens in the treatment of idiopathic membranous nephropathy (IMN). Methods: After systematically searched associated studies up to 1st December 2020, we performed a fixed and random-effects meta-analysis using the Stata software and evaluated the quality of included studies by the risk of bias scale of the Cochrane collaboration tool. Results: RTX had a higher total remission (TR) (OR = 2.663, 95% CI 1.361 to 5.210, P = 0.004) than conventional therapy for patients at moderate risk for lose of kidney function (pre-study proteinuria < 8 g/d), however, for patients at severe risk (pre-study proteinuria > 8 g/d), there was no significant difference in TR (OR = 0.691, 95% CI 0.064 to 7.423, P = 0.761). In RTX dose studies, standard dose regimen had a better effect of reducing proteinuria than low-dose regimen (Low dose MD = -3.999, 95% CI -6.177 to -1.820; standard dose MD = -5.220, 95% CI -7.160 to -3.279, P < 0.0001). Significant improvement in serum albumin was seen in patients treated with standard dose than low dose regimen (Low dose MD = 0.601, 95% CI 0.052 to 1.150, P = 0.032; standard dose MD = 0.963, 95% CI 0.740 to 1.185, P < 0.0001). Conclusion: For patients with moderate risk IMN, RTX treatment has a higher TR than conventional therapy. Standard dose RTX is more effective than low dose in reducing proteinuria and recovering serum albumin levels.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Nessrine Breik ◽  
Mouna Jerbi ◽  
Raja Aoudia ◽  
Soumaya Chargui ◽  
Hanen Guaied ◽  
...  

Abstract Background and Aims Idiopathic membranous nephropathy (IMN) is increasingly seen in older patients but little is known about its treatment and outcomes at long term follow up. The objective of this work is to study the renal survival of IMN in elderly as well as prognostic factors. Method We conducted a retrospective descriptive study in the nephrology department at Charles Nicolle hospital over a period of 44 years. All older patients (≥65 years) with histologically proven MN were included in this study. Data collected included demographic, clinical and biological parameters in each patient. Data were entered and analyzed using SPSS software. Chi-squared test with a level of significance of 0.05 was used for the qualitative variables. Results Twenty-eight patients were collected. The mean age was 67.03 years (65-78 years) with a male predominance (sex ratio: 2.3) and low socio-economic level in 82.5% of cases. Sixteen patients were smokers (57.14%), 5 ethyl patients (17.8%), diabetes was present in 3 patients (10.7%) and hypertension in 11 patients (39.28%). The clinico-biological picture was dominated by high systolic blood pressure in 21 cases (75%), anasarca in 7 cases (25%), proteinuria in all cases and hematuria in 20 cases (71.14%). Biology revealed nephrotic syndrome (NS) in all cases, hypercholesterolemia in 23 cases (82.14%), high serum creatinine in 14 cases (50%) with an average creatinine level of 127,95 µmol/l, anemia in 17 cases (60.7%) and anti-neutrophil cytoplasmic antibodies were positive in one case. MN was confirmed by a kidney biopsy in all cases. Symptomatic treatment was indicated in all patients. Immunosuppressive therapy was started early in 12 patients (40%) because of the severe NS and the deterioration of renal function. Eight patients (26.6%) received corticosteroids alone, three patients received corticosteroid with mycofenolate mofetil and one patient received corticosteroid with ciclosporin. Fourteen patients received only symptomatic treatment. We noted complete remission in 6 patients (21.42%) and end renal stage disease in 5 patients (17.85%). Our study showed that treatment with angiotensin receptors blockers was associated with better renal survival with a statistically significant difference, (p = 0.011). A reduced kidney function at presentation, tubule-interstitial disease and interstitial fibrosis and tubular atrophy were associated with poor survival with a statistically significant result (p = 0.012) (p=0,011) respectively. Conclusion IMN is the most common cause of nephrotic syndrome in elderly patients and it has the same risk for progression as in younger individuals. Decrements in glomerular filtration rate, increased risk for comorbidities, vascular disease and change in pharmacokinetics justify special attention to treatment decisions in elderly individuals with IMN.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xianding Wang ◽  
Fan Zhang ◽  
Yamei Jiang ◽  
Zilin Xu ◽  
Xiaobing Feng ◽  
...  

Abstract Background Currently, research on the quantitative distribution of ABO antigens in different organs and tissues remains limited. We aimed to examine the individual characteristics of blood group glycoprotein A and B antigen expression in human kidneys and livers. Methods We obtained human samples, including the renal artery, renal vein, renal tissue, hepatic artery, hepatic vein, portal vein, and hepatic tissue, from 24 deceased organ transplant donors. The expression of the blood group antigens glycoprotein A and B was analysed and compared by Western blotting. Results There was no significant difference in the expression between blood group glycoprotein A and B antigens at any of the seven sites (p > 0.05). The expression of both A and B antigens was highest in renal tissue and the portal vein and was lowest in the renal artery. A large difference in glycoprotein antigen expression was observed among various donors or different regions of the same individual. Univariate analysis revealed that glycoprotein A/B antigens were affected by the age and sex of donors and were significantly higher in males and in young people. Conclusions Our study found that blood group glycoprotein antigen expression showed certain trends and distinct distribution in the kidney, liver, and vessels among individuals and in different regions of the same individual, which may explain the different clinical outcomes of patients who received ABO-incompatible transplantation.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8650 ◽  
Author(s):  
Wenkai Guo ◽  
Yan Zhang ◽  
Caifeng Gao ◽  
Jing Huang ◽  
Jiatong Li ◽  
...  

Background To discuss the clinicopathological features and prognosis of patients with idiopathic membranous nephropathy (IMN) who are serum-negative for the anti-PLA2R antibody. Method Overall, 229 IMN patients were retrospectively collected in this study and classified into anti-PLA2R antibody-negative (PLA2R−, 59 cases) and antibody-positive (PLA2R+, 170 cases) groups. The clinical and pathological features of the PLA2R− group were analyzed; 162 patients in both groups were followed up, and the PLA2R antigen was detected in renal biopsies from the PLA2R− group. Kaplan-Meier and survival analyses were used to compare differences in prognosis. Results Serum albumin levels were higher and 24-hour urine protein, creatinine, and beta 2-microglobulin (BMG) levels were lower in the PLA2R− group than in the PLA2R+ group; the proportion of acute and chronic tubular lesions was also significantly lower in the PLA2R− group than in in the PLA2R+ group. After treatment, the remission rate was significantly higher in the negative group than in the positive group (93.02% vs 74.78%,), especially the rate of complete remission (51.16% vs 23.47%). Furthermore, the PLA2R antigen-positive staining rate of 43 patients in the PLA2R− group was 62.79%. Although not significant, the survival rate was higher in the PLA2R− group than in the PLA2R+ group. BMG, 24-hour urine protein and acute and chronic tubular lesions were risk factors for kidney death, and 24-hour urine protein was an independent risk factor for kidney death. Conclusions Compared with the PLA2R+ group, the PLA2R− group had mild clinical manifestations and pathological damage and a higher clinical treatment remission rate. Renal tissue PLA2R antigen testing can be considered for patients with seronegative IMN to increase the diagnostic rate.


2021 ◽  
Vol 12 ◽  
Author(s):  
Zhaocheng Dong ◽  
Haoran Dai ◽  
Yu Gao ◽  
Hanxue Jiang ◽  
Meiqi Liu ◽  
...  

Objective: To explore the clinical effect of Mahuang Fuzi and Shenzhuo Decoction on idiopathic membranous nephropathy.Methods: This study is a multicenter, nonrandomized, single-arm clinical trial carried out as per the objective performance criteria, with the target being set at 35.0%. 184 cases of patients suffering from idiopathic membranous nephropathy with Shaoyin Taiyin syndrome were collected. These patients were treated with Mahuang Fuzi and Shenzhuo Decoction with a follow-up period of 3 years. The 24-hour urine protein and blood albumin were observed, and the remission rates of the patients were compared with the target.Results: The mean follow-up time was 18 (12.5, 30) months, and the remission rate was 61.4%, which is a statistically significant difference from the target group of 35%. The remission rates for patients who had and had not used immunosuppressive therapy were 59.6 and 65.5%, respectively, but the difference was not statistically significant (p = 0.254). However, the albumin before the treatment and the course of treatment of the patients was significantly correlated with the disease remission (p &lt; 0.05). However, the albumin before the treatment and the course of treatment of the patients was significantly correlated with the disease remission (p &lt; 0.05). There were no significant changes in renal function before and after treatment, and no severe adverse events occurred during treatment.Conclusion: Mahuang Fuzi and Shenzhuo Decoction have significant effects on idiopathic membranous nephropathy, and has the same effect on patients with membranous nephropathy who are newly treated as well as those who have been treated with immunosuppressive therapy without remission. In addition, the efficacy of this regimen is related to the albumin and the duration of the therapy, but not to 24-hour urine protein or other factors.


Sign in / Sign up

Export Citation Format

Share Document