Response Predictors to Calcineurin Inhibitors in Patients with Primary Membranous Nephropathy

2018 ◽  
Vol 47 (4) ◽  
pp. 266-274 ◽  
Author(s):  
Xiaofang Yu ◽  
Jieru Cai ◽  
Xiaoyan Jiao ◽  
Shu Zhang ◽  
Hong Liu ◽  
...  
Keyword(s):  
Roc Curve ◽  
Membranous Nephropathy ◽  
Minimal Change Disease ◽  
Operating Characteristic ◽  
Calcineurin Inhibitors ◽  
Minimal Change ◽  
Ms Analysis ◽  
Response Predictors ◽  
Phospholipase A2 Receptor ◽  
Serum Amyloid A1

Background: Currently, there is an urgent need to find ways of identifying primary membranous nephropathy (PMN) patients who are likely to benefit from calcineurin inhibitors (CNI) or who are resistant to them. In this study, we employed nano-HPLC-MS/MS analysis to identify serum biomarkers that predict the clinical response to CNI therapy in PMN patients. Methods: The endpoint was complete remission (CR) after CNI treatment. PMN patients were grouped into no-remission (NR) or CR groups to screen predictive candidates using the nano-HPLC-MS/MS analysis. Results: Compared with NR patients, 3 upregulated proteins and 5 downregulated proteins were found to present a twofold change in CR patients’ serum. Serum amyloid A1 protein (SAA1) was further validated by ELISA; it was decreased in patients in the NR group compared with patients in the CR group, but SAA1 in patients in these groups was lower than in healthy controls and minimal change disease patients. The area under the receiver operating characteristic (ROC) curve of SAA1 was used to distinguish PMN NR patients from those in remission and was 0.901, with a sensitivity of 78.3% and specificity of 86.8%, similar to that of the phospholipase A2 receptor (PLA2R) antibody. Combining SAA1 with the PLA2R antibody, the area under the ROC curve was 0.956, which was higher than that of SAA1 or the PLA2R antibody alone. Conclusions: Serum SAA1 may be a candidate PMN biomarker that can be used to discriminate CNI NR cases from remission patients. The combination of SAA1 and the PLA2R antibody increases the accuracy of diagnosis.

scholarly journals Development and Validation of a Discrimination Model Between Primary PLA2R-Negative Membranous Nephropathy and Minimal Change Disease Confirmed by Renal Biopsy

2020 ◽  
Author(s):  
Feng Wu ◽  
Yiding Zhang ◽  
Wen Cui ◽  
Yijun Dong ◽  
Yingyang Geng ◽  
...  
Keyword(s):  
Renal Biopsy ◽  
Membranous Nephropathy ◽  
Minimal Change Disease ◽  
Multivariate Logistic Regression Analysis ◽  
Test Group ◽  
Minimal Change ◽  
Clinical Feature ◽  
Specific Marker ◽  
Discrimination Model ◽  
Phospholipase A2 Receptor

Abstract BackgroundMembranous nephropathy (MN) and minimal change disease (MCD) are two common causes leading to nephrotic syndrome (NS). They have similar clinical feature but different treatment strategy and prognosis. M-type phospholipase A2 receptor (PLA2R) is considered as a specific marker of membranous nephropathy. However, its sensitivity is only about 70%. Therefore, there is a lack of effective and noninvasive tools to distinguish PLA2R-negative MN and MCD patients without renal biopsy. We aim to develop a discrimination model using noninvasive parameters for distinguishing the two diseases and support immediate treatment before result of renal biopsy.MethodsA total 949 patients who were pathologically diagnosed as idiopathic MN or primary MCD in the First Affiliated Hospital of Zhengzhou University from January 2017 to August 2019 were enrolled in this study, including 805 idiopathic MN (605 PLAR2-positive MN and 200 PLA2R-negative MN) and 144 primary MCD. Based on the basic information and laboratory examination of 200 PLA2R-negative MN and 144 MCD, we used univariate and multivariate logistic regression analysis to select the relevant variables and develop the discrimination model. ROC curves and calibration curves were used to evaluate the diagnostic ability and calibration ability of the model. The decision curve was used to show the net benefit. We also tested the effectiveness of our model in all 949 patients.ResultsA novel model that included age, albumin, urea, high density lipoprotein, urea and red blood cell count was established for PLA2R-negative MN and MCD. The discrimination model has good differential capability (an AUC of 0.889 in training group and an AUC of 0.920 in test group) and calibration capability. When testing in all 949 patients, our model also showed good discrimination ability for all idiopathic MN and MCD.ConclusionWe constructed a discrimination model with high diagnostic effectiveness for PLA2R-negative MN and MCD. The model could also be used for all idiopathic MN and MCD patients.

scholarly journals Development and validation of a discrimination model between primary PLA2R-negative membranous nephropathy and minimal change disease confirmed by renal biopsy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Feng Wu ◽  
Yiding Zhang ◽  
Wen Cui ◽  
Yijun Dong ◽  
Yingyang Geng ◽  
...  
Keyword(s):  
Renal Biopsy ◽  
Membranous Nephropathy ◽  
Minimal Change Disease ◽  
Treatment Strategies ◽  
Test Group ◽  
Minimal Change ◽  
Specific Marker ◽  
Discrimination Ability ◽  
Discrimination Model ◽  
Phospholipase A2 Receptor

AbstractMembranous nephropathy (MN) and minimal change disease (MCD) are two common causes leading to nephrotic syndrome (NS). They have similar clinical features but different treatment strategies and prognoses. M-type phospholipase A2 receptor (PLA2R) is considered as a specific marker of membranous nephropathy. However, its sensitivity is only about 70%. Therefore, there is a lack of effective and noninvasive tools to distinguish PLA2R-negative MN and MCD patients without renal biopsy. A total 949 patients who were pathologically diagnosed as idiopathic MN or MCD were enrolled in this study, including 805 idiopathic MN and 144 MCD. Based on the basic information and laboratory examination of 200 PLA2R-negative MN and 144 MCD, we used a univariate and multivariate logistic regression to select the relevant variables and develop a discrimination model. A novel model including age, albumin, urea, high density lipoprotein, C3 levels and red blood cell count was established for PLA2R-negative MN and MCD. The discrimination model has great differential capability (with an AUC of 0.904 in training group and an AUC of 0.886 in test group) and calibration capability. When testing in all 949 patients, our model also showed good discrimination ability for all idiopathic MN and MCD.

scholarly journals Development and Validation of a Between Primary PLA2R-Negative Membranous Nephropathy and Minimal Change Disease Confirmed by Renal Biopsy

2021 ◽  
Author(s):  
Feng Wu ◽  
Yiding Zhang ◽  
Wen Cui ◽  
Yijun Dong ◽  
Yingyang Geng ◽  
...  
Keyword(s):  
Renal Biopsy ◽  
Membranous Nephropathy ◽  
Minimal Change Disease ◽  
Test Group ◽  
Minimal Change ◽  
Clinical Feature ◽  
Specific Marker ◽  
Net Benefit ◽  
Discrimination Model ◽  
Phospholipase A2 Receptor

Abstract Background: Membranous nephropathy (MN) and minimal change disease (MCD) are two common causes leading to nephrotic syndrome (NS). They have similar clinical feature but different treatment strategy and prognosis. M-type phospholipase A2 receptor (PLA2R) is considered as a specific marker of membranous nephropathy. However, its sensitivity is only about 70%. Therefore, there is a lack of effective and noninvasive tools to distinguish PLA2R-negative MN and MCD patients without renal biopsy. We aim to develop a discrimination model using noninvasive parameters for distinguishing the two diseases and support immediate treatment before result of renal biopsy.Methods: A total 949 patients who were pathologically diagnosed as idiopathic MN or primary MCD in the First Affiliated Hospital of Zhengzhou University from January 2017 to August 2019 were enrolled in this study, including 805 idiopathic MN (605 PLAR2-positive MN and 200 PLA2R-negative MN) and 144 primary MCD. Based on the basic information and laboratory examination of 200 PLA2R-negative MN and 144 MCD, we used a univariate and multivariate logistic regression to select the relevant variables and develop the discrimination model. ROC curve and calibration curve were used to evaluate the diagnostic ability and calibration ability of the model. The decision curve was used to calculate the net benefit. We also test the effectiveness of our model in all 949 patients.Results: A novel model that included age, albumin, urea, high density lipoprotein, urea and red blood cell count was established for PLA2R-negative MN and MCD. The discrimination model has excellent differential capability (an AUC of 0.889 in training group and an AUC of 0.920 in test group) and calibration capability. When testing in all 949 patients, our model also showed good discrimination ability for all idiopathic MN and MCD.Conclusion: We constructed a discrimination model with high diagnostic effectiveness for PLA2R-negative MN and MCD. The model could also be used for all idiopathic MN and MCD patients.

Comparison of treatment options in adults with frequently relapsing or steroid-dependent minimal change disease

2020 ◽  
Author(s):  
Cihan Heybeli ◽  
Stephen B Erickson ◽  
Fernando C Fervenza ◽  
Marie C Hogan ◽  
Ladan Zand ◽  
...  
Keyword(s):  
Median Time ◽  
Minimal Change Disease ◽  
Treatment Options ◽  
Calcineurin Inhibitors ◽  
Immunosuppressive Drugs ◽  
Minimal Change ◽  
Line Treatment ◽  
Second Line ◽  
Steroid Dependent ◽  
Time To Relapse

Abstract Background Studies comparing all treatment options for frequently-relapsing/steroid-dependent (FR/SD) minimal change disease (MCD) in adults are lacking. Methods Medical records of 76 adults with FR/SD MCD who were treated with corticosteroids as the first-line therapy were reviewed. Treatment options were compared for the time to relapse, change of therapy and progression (relapse on full-dose treatment). Results Second-line treatments included rituximab (RTX; n = 13), mycophenolate mofetil (MMF; n = 12), calcineurin inhibitors (CNI; n = 26) and cyclophosphamide (CTX; n = 16). During the second-line treatments, 48 (71.6%) patients relapsed at median 17 (range 2–100)  months. The majority of relapses occurred during dose tapering or off drug. Twenty of 65 (30.8%) changed therapy after the first relapse. The median time to relapse after the second line was 66 versus 28 months in RTX versus non-RTX groups (P = 0.170). The median time to change of treatment was 66 and 44 months, respectively (P = 0.060). Last-line treatment options included RTX (n = 8), MMF (n = 4), CNI (n = 3) and CTX (n = 2). Seven (41.2%) patients had a relapse during the last-line treatment at median 39 (range 5–112)  months. The median time to relapse was 48 versus 34 months in the RTX versus non-RTX groups (P = 0.727). One patient in the RTX group died presumably of heart failure. No major adverse event was observed. During the median follow-up of 81 (range 9–355)  months, no patients developed end-stage renal disease. Conclusions Relapse is frequent in MCD in adults. Patients treated with RTX may be less likely to require a change of therapy and more likely to come off immunosuppressive drugs.

scholarly journals A diagnostic model for minimal change disease based on biological parameters

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4237 ◽  
Author(s):  
Hanyu Zhu ◽  
Qiuxia Han ◽  
Dong Zhang ◽  
Yong Wang ◽  
Jing Gao ◽  
...  
Keyword(s):  
Minimal Change Disease ◽  
Density Lipoprotein ◽  
Diagnostic Value ◽  
Minimal Change ◽  
Lipoprotein Cholesterol ◽  
Control Group ◽  
Diagnostic Model ◽  
Thrombin Time ◽  
Biological Parameters ◽  
Phospholipase A2 Receptor

Background Minimal change disease (MCD) is a kind of nephrotic syndrome (NS). In this study, we aimed to establish a mathematical diagnostic model based on biological parameters to classify MCD. Methods A total of 798 NS patients were divided into MCD group and control group. The comparison of biological indicators between two groups were performed with t-tests. Logistic regression was used to establish the diagnostic model, and the diagnostic value of the model was estimated using receiver operating characteristic (ROC) analysis. Results Thirteen indicators including Anti-phospholipase A2 receptor (anti-PLA2R) (P = 0.000), Total protein (TP) (P = 0.000), Albumin (ALB) (P = 0.000), Direct bilirubin (DB) (P = 0.002), Creatinine (Cr) (P = 0.000), Total cholesterol (CH) (P = 0.000), Lactate dehydrogenase (LDH) (P = 0.007), High density lipoprotein cholesterol (HDL) (P = 0.000), Low density lipoprotein cholesterol (LDL) (P = 0.000), Thrombin time (TT) (P = 0.000), Plasma fibrinogen (FIB) (P = 0.000), Immunoglobulin A (IgA) (P = 0.008) and Complement 3 (C3) (P = 0.019) were significantly correlated with MCD. Furthermore, the area under ROC curves of CH, HDL, LDL, TT and FIB were more than 0.70. Logistic analysis demonstrated that CH and TT were risk factors for MCD. According to the ROC of “CH+TT”, the AUC was 0.827, with the sensitivity of 83.0% and the specificity of 69.8% (P = 0.000). Conclusion The established diagnostic model with CH and TT could be used for classified diagnosis of MCD.

scholarly journals P0468RENAL OUTCOME AND MORTALITY OF GLOMERULONEPHRITIS IN A THAI TERTIARY CARE CENTER

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Chitimaporn Janphram ◽  
Chagriya Kitiyakara
Keyword(s):  
Multiple Myeloma ◽  
Diabetic Nephropathy ◽  
Lupus Nephritis ◽  
Iga Nephropathy ◽  
Immune Complex ◽  
Membranous Nephropathy ◽  
Minimal Change Disease ◽  
Kidney Biopsy ◽  
Minimal Change ◽  
Different Types

Abstract Background and Aims Glomerulonephritis (GN) is a common cause of End-stage renal disease (ESRD) in Asia and around the world. Most studies from renal registries have focused on the prevalence or clinical characteristics of patients with GN. Only a few registry-based data have focused on mortality and ESRD risks of different types of GN. There is limited data from low to middle income countries or from Southeast Asia. The objectives of this study were to evaluate the mortality and ESRD rates among patients with different types of GN referred for a kidney biopsy at a Thai tertiary care hospital. Method In this retrospective study, the data of patients (n=1,025) referred for a kidney biopsy at Ramathibodi Hospital from 1 January 2011 to 31 December 2017 were reviewed. Patients were classified in to 11 different types of GN. Patient death and cause of death data was obtained from National Census office. ESRD data was obtained from the Thailand Nephrology Society ESRD registry which includes all patients on renal replacement therapies for greater than 3 months. Results Patients with inadequate specimen (n=66) or non-glomerular diseases (n=95) were excluded. Data from 864 patients with GN was analyzed. The age at kidney biopsy was 43.9 ± 16.8 years, median eGFR (CKD-EPI) was 42 (IQR 13-83) mL/min/1.73m2. The male:female ratio was 0.6. The prevalence of GN were: Lupus nephritis (26.8%), IgA nephropathy (18.2%), focal segmental glomerulosclerosis (FSGS 12.6 %), membranous nephropathy (11.9 %), diabetic nephropathy (10.8%), minimal change disease (9.7%), hypertensive nephrosclerosis (4.3%), pauci-immune complex glomerulonephritis (2.3%), membranoproliferative glomerulonephritis (MPGN 1.6%) and multiple myeloma (1.4%) Median time follow up was 42 (IQR 23-62) months. Overall mortality was 13 %. Lupus nephritis accounted for highest proportion of all deaths (25%), followed by diabetic nephropathy (19.1%), FSGS (9%). Listed causes of deaths were: sepsis 22% and chronic kidney disease 8%. Mortality rates by disease were: multiple myeloma (50%), diabetic nephropathy (28.7%), MPGN (21.4%), pauci-immune complex GN (20%), hypertensive nephrosclerosis (15.8%), lupus nephritis (14.6%), membranous nephropathy (8.7%), FSGS (8.2%), minimal change disease (5.8%), IgA nephropathy (4.4%) The incidence of ESRD was 14 %. LN accounted for the highest proportion (29%) of all ESRD, followed by IgA nephropathy (14%), and membranous nephropathy (13%). The rates of ESRD by disease were: multiple myeloma (33.3%), lupus nephritis (15%), membranous nephropathy (14.5%), minimal change disease (14.3%), MPGN (14.2%), IgA nephropathy (10.1%), FSGS (10.1%), diabetic nephropathy (7.4%), pauci-immune complex glomerulonephritis (5%), hypertensive nephroclerosis (2.6%). Conclusion Lupus nephritis is the most common GN and accounted for the highest proportion of all deaths and ESRD in this Thai cohort. IgA nephropathy is the most common primary GN and an important cause of ESRD, but the mortality rate is low compared to other GN. Membranous nephropathy has comparable prevalence to FSGS, but is a more important contributor to ESRD. Diabetic nephropathy has higher rate of mortality than ESRD. Multiple myleloma has the highest rate of both death and ESRD.

The Primary Glomerular Diseases

2017 ◽  
Author(s):  
Richard J. Glassock ◽  
Sanjeev Sethi ◽  
Fernando C. Fervenza
Keyword(s):  
Renal Biopsy ◽  
Membranous Nephropathy ◽  
Minimal Change Disease ◽  
Crescentic Glomerulonephritis ◽  
Minimal Change ◽  
C3 Glomerulonephritis ◽  
Focal And Segmental Glomerulosclerosis ◽  
Glomerular Diseases ◽  
Dense Deposit ◽  
Primary Glomerular Diseases

Glomerular disorders in which the manifestations of disease are primarily confined to the kidneys, without multisystem involvement, are not only common but very heterogeneous in terms of pathogenesis and clinical features. Typically, these primary glomerular diseases are characterized according to the findings on renal biopsy, as studied by light, immunofluorescence, and electron microscopy. The principal primary glomerular diseases are minimal change disease, focal and segmental glomerulosclerosis, membranous nephropathy, C3 glomerulonephritis and dense deposit disease, IgA nephropathy, and renal-limited crescentic glomerulonephritis. These clinicopathologic entities are discussed according to epidemiology, clinical features, pathology, pathogenesis (and genetics if appropriate), prognosis, and treatment, emphasizing recent findings.  Key words: C3 glomerulonephritis, dense deposit disease, focal and segmental glomerulosclerosis, glomerulonephritis, IgA nephropathy, membranous nephropathy, minimal change disease, renal biopsy, renal-limited crescentic glomerulonephritis

scholarly journals Loss of phosphatidylserine flippase β-subunit Tmem30a in podocytes leads to albuminuria and glomerulosclerosis

2021 ◽  
Author(s):  
Wenjing Liu ◽  
Lei Peng ◽  
Wanli Tian ◽  
Yi Li ◽  
Ping Zhang ◽  
...  
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Membranous Nephropathy ◽  
Minimal Change Disease ◽  
Critical Role ◽  
Minimal Change ◽  
Mouse Retina ◽  
Β Subunit ◽  
Filtration Barrier ◽  
Segmental Glomerulosclerosis

Phosphatidylserine (PS) is asymmetrically concentrated in the cytoplasmic leaflet of eukaryotic cell plasma membranes. This asymmetry is regulated by a group of P4 ATPases (named PS flippases) and its β-subunit TMEM30A. The disruption of PS flippase leads to severe human diseases. Tmem30a is essential in the mouse retina, cerebellum and liver. However, the role of Tmem30a in the kidney, where it is highly expressed, remains unclear. Podocytes in the glomerulus form a branched interdigitating filtration barrier that can prevent the traversing of large cellular elements and macromolecules from the blood into the urinary space. Damage to podocytes can disrupt the filtration barrier and lead to proteinuria and podocytopathy, including focal segmental glomerulosclerosis, minimal change disease, membranous nephropathy, and diabetic nephropathy. We observed reduced TMEM30A expression in patients with minimal change disease and membranous nephropathy, indicating potential roles of TMEM30A in podocytopathy. To investigate the role of Tmem30a in the kidney, we generated a podocyte-specific Tmem30a knockout (KO) mouse model using the NPHS2-Cre line. Tmem30a KO mice displayed albuminuria, podocyte degeneration, mesangial cell proliferation with prominent extracellular matrix accumulation and eventual progression to focal segmental glomerulosclerosis (FSGS). Our data demonstrate a critical role of Tmem30a in maintaining podocyte survival and glomerular filtration barrier integrity. Understanding the dynamic regulation of the PS distribution in the glomerulus provides a unique perspective to pinpoint the mechanism of podocyte damage and potential therapeutic targets.

The evolution of the therapeutic approach to membranous nephropathy

2020 ◽  
Author(s):  
Claudio Ponticelli ◽  
Passerini Patrizia ◽  
Lucia Del Vecchio ◽  
Francesco Locatelli
Keyword(s):  
Membranous Nephropathy ◽  
Alkylating Agent ◽  
Randomized Clinical Trials ◽  
Calcineurin Inhibitors ◽  
Phospholipase A2 Receptor ◽  
Repeated Administrations ◽  
Circulating Antibodies ◽  
Stage Renal Disease ◽  
End Stage

Abstract Primary membranous nephropathy (MN) is a frequent cause of nephrotic syndrome (NS) in adults. In untreated patients, the outcome is variable, with one-third of the patients entering remission while the remaining ones show persisting proteinuria or progression to end-stage renal disease. Randomized clinical trials reported the efficacy of a 6-month regimen alternating intravenous and oral glucocorticoids with an alkylating agent every other month. The potential side effects of this regimen were limited by the fact that the use of glucocorticoids and alkylating agent did not exceed 3 months each. Two randomized trials with follow-ups (FU) up to 10 years provided assurance about the long-term efficacy and safety of this cyclical therapy. Calcineurin inhibitors have also been used successfully. However, in most responders, NS relapsed after the drug was withdrawn. Conflicting results have been reported with mycophenolate salts and adrenocorticotropic hormone. Observational studies reported good results with rituximab (RTX). Two controlled trials demonstrated the superiority of RTX over antiproteinuric therapy alone and cyclosporine. However, the FUs were relatively short and no randomized trial has been published against cyclical therapy. The available results, together with the discovery that most patients with MN have circulating antibodies against the phospholipase A2 receptor 1, support the use of cytotoxic drugs or RTX in MN. It is difficult to choose between these two different treatments. RTX is easier to use, but the FUs of the available studies are short, thus doubts remain about the long-term risk of relapses and the safety of repeated administrations of RTX.

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