Primary Membranous Nephropathy (original) (raw)
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International Journal of Clinical Practice, 2020
Background Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in nondiabetic adults. M-type phospholipase A2 receptor (PLA2R), thrombospondin type-1 domain-containing 7A (THSD7A) are known as target podocyte antigens in membranous nephropathy (MN). Antibodies against these podocyte antigens are used in the initiation of treatment and response monitoring. However, the relationship between renal podocyte antigens and treatment response is not clear yet. We evaluated the relationship between immunohistochemical PLA2R, THSD7A, and IgG4 staining, clinical findings, and treatment response in kidney biopsies. Methods Fifty-eight patients with MN were included in this retrospective study. In the renal biopsy samples of the patients, PLA2R, THSD7A, and IgG4 were stained immunohistochemically and evaluated by light microscopy. The clinical, laboratory, and treatment results of the patients were obtained from the hospital records.
ANTI-PLA2R ANTIBODY AND PRIMARY MEMBRANOUS NEPHROPATHY: A LITERATURE REVIEW (Atena Editora)
ANTI-PLA2R ANTIBODY AND PRIMARY MEMBRANOUS NEPHROPATHY: A LITERATURE REVIEW (Atena Editora), 2023
Membranous nephropathy is the most common cause of nephrotic syndrome in non-diabetic Caucasian adults over 40 years of age and a leading cause of nephrotic syndrome in adults. Classified into primary and secondary membranous nephropathy related to various conditions including infection (hepatitis B), systemic disease (SLE and sarcoidosis), medications (nonsteroidal anti-inflammatory drugs), thyroiditis, and malignancy. Evidence of the clinical utility of measuring PLA2R plasma levels has increased over the last 2 years and was the main focus of this review. The guiding question was: “What is the clinical applicability of the anti-PLA2R antibody in the management of primary membranous nephropathy, as reported in the literature?”. The literature review was developed following the PICO search strategy. All patients with primary membranous nephropathy must be treated with supportive care from the time of diagnosis to minimize protein excretion. Patients with elevated anti-PLA2R levels and proteinuria >3.5 g/d at diagnosis and those who fail to reduce proteinuria to <3.5 g after 6 months of supportive care or have complications of nephrotic syndrome must be considered for immunosuppressive therapy. Accepted regimens include steroids/cyclophosphamide, calcineurin inhibitors, and B-cell depletion. The anti-PLA2R antibody is the first serological marker that has promising evidence to be used as a tool to predict the course of the disease. More importantly, therapeutic agents such as rituximab and adrenocorticotropic hormone analogues are new therapeutic options that must be considered in the therapy of primary MN.
Membranous nephropathy: diagnosis, treatment, and monitoring in the post-PLA2R era
Pediatric Nephrology, 2019
Membranous nephropathy (MN) is an immune complex-mediated cause of the nephrotic syndrome that can occur in all age groups, from infants to the very elderly. However, nephrotic syndrome in children is more frequently caused by conditions such as minimal change disease or focal segmental glomerulosclerosis, and much less commonly by MN. While systemic conditions such as lupus or infections such as hepatitis B may more commonly be associated as secondary causes with MN in the younger population, primary or "idiopathic" MN has generally been considered a disease of adults. Autoantibodies both to the M-type phospholipase A2 receptor (PLA2R) and to thrombospondin type-1 domain-containing 7A (THSD7A), initially described in adult MN, have now been identified in children and adolescents with MN and serve as a useful diagnostic and monitoring tool in this younger population as well. Whereas definitive therapy for secondary forms of MN should be targeted at the underlying cause, immunosuppressive therapy is often necessary for primary disease. Rituximab has been successfully used in the treatment of MN, and is likely effective in children with MN as well, although dosing in the pediatric population is not well established. This review highlights the new findings in adult and pediatric MN since last reviewed in this journal.
Anti-PLA2R-associated membranous nephropathy: a review with emphasis on diagnostic testing methods
Clinical Nephrology, 2015
The majority of cases of primary membranous nephropathy (MN) are associated with auto-antibodies against the podocyte antigen M-type phospholipase A2 receptor (PLA2R). This particular subset of MN can be diagnosed by identifying anti-PLA2R within patient sera or by detecting PLA2R antigen within glomerular immune complexes in renal biopsy tissue. Since the discovery of anti-PLA2R in 2009, there has been an abundance of literature regarding PLA2R testing as a tool in the diagnosis and management of MN, and these tests are increasingly being implemented in clinical practice. However, questions still remain about a variety of issues such as PLA2R testing in the setting of presumably secondary MN and the significance of PLA2R negative primary MN. The goal of this review is to summarize the current PLA2R testing methods and highlight special features of anti-PLA2R-associated MN.
Anti-PLA2R Antibodies as a Prognostic Factor in PLA2R-Related Membranous Nephropathy
American journal of nephrology, 2015
The natural course of idiopathic membranous nephropathy (MN) varies, as it is known through favorable outcomes in most patients. However, one third of patients with idiopathic MN will slowly progress to end-stage renal disease (ESRD). To prevent disease progression, patients at high risk to develop ESRD are treated with immunosuppressive agents. Therefore, a correct selection of patients who need immunosuppressive treatment is important. Here, we evaluated the prognostic value of anti-phospholipase A2 receptor 1 antibody (anti-PLA2R) levels regarding clinical outcome in a well-defined cohort of 73 PLA2R-related MN patients with long-term follow-up. At baseline, patients were subdivided into patients with either low or high antibody levels based on ELISA testing. Spontaneous remission rates were highest among patients with low anti-PLA2R levels (79%; hazard ratio 2.72 (95% CI 1.22-6.08), p = 0.02) after a median follow-up of 2.9 (95% CI 0.8-5.0, p < 0.001) years, whereas high anti...
American journal of clinical pathology, 2014
Autoantibodies against the M-type phospholipase A2 receptor 1 (anti-PLA2R1) have been demonstrated to be very specific for idiopathic membranous nephropathy (MN). We studied a novel enzyme-linked immunosorbent assay (ELISA) and compared results with results obtained using an indirect immunofluorescence (IIF) and a Western blotting test (WB). One-hundred nine patients with idiopathic MN were recruited between November 1979 and March 2011. The control cohort comprised serum samples from patients with secondary MN (n = 16) and nephrotic controls (n = 17). The presence of anti-PLA2R1 in serum samples obtained at the time of renal biopsy was determined using ELISA, IIF, and WB. With similar specificity (≥ 97%), sensitivity varied from 68% (IIF) to 72% (ELISA, WB). Remarkably, patients who were seronegative for anti-PLA2R1 more often entered spontaneous remission (P = .038), whereas seropositive patients were more frequently treated with immunosuppressive agents (P < .001). ELISA perfo...
PloS one, 2017
Clinical course of membranous nephropathy (MN) is difficult to predict. Measurement of circulating anti-PLA2R autoantibodies (PLA2R-Ab) and detection in immune deposits of PLA2R antigen (PLA2R-Ag) are major advances in disease understanding. We evaluated the clinical significance of these biomarkers. In this 14-year retrospective study, we collected data from 108 MN patients and assessed the relationship between clinical course, PLA2R-Ab and PLA2R-Ag. We also assessed THSD7A status. Eighty-five patients suffered from primary MN (PMN) and 23 patients from a secondary form. The median follow-up was 30.4 months [interquartile range, 17.7;56.7]. Among the 77 patients with PMN and available serum and/or biopsy, 69 (89.6%) had PLA2R-related disease as shown by anti-PLA2R-Ab and/or PLA2R-Ag, while 8 patients (8/77, 10.4%) were negative for both. There was no significant difference between these two groups in age at diagnosis and outcome assessed by proteinuria, serum albumin level and eGFR...
Kidney International Reports, 2017
Introduction: Autoantibodies to M-type phospholipase A2 receptor (aPLA2R) are seen in two-thirds of patients with primary membranous nephropathy (PMN) and are associated with disease activity. However, the precise temporal dynamics between the presence and amount of aPLA2R in circulation, as well as the clinical activity, are not known. We evaluated the temporal association between disease activity and serum aPLA2R during and after treatment in PMN. Methods: The study included all patients with PMN and elevated aPLA2R who were started on immunosuppressive therapy for persistent nephrotic syndrome at a single center between December 2014 and December 2015. Serum samples were tested for aPLA2R at baseline and at monthly intervals for 6 months. Clinical details were collected monthly for 9 months. Serological remission was defined as negative aPLA2R in 2 consecutive samples. Clinical remission was defined by standard criteria. Results: A total of 30 patients with PMN were studied. Of these, 28 (93%) had elevated levels at baseline, whereas 2 (7%) became positive after 1 month. The mean age was 33.2 AE 1 (range, 13À52) years. Median baseline aPLA2R titer was 163.41 (range, 70À291.01) RU/ml. A total of 24 patients (80%) achieved serological remission by 6 months. Among all the serological responders, 54% had achieved negative aPLA2R by the end of the first month. Clinical remission was observed in 20 patients (67%). Serological and clinical remission were noted at 2.7 AE 1.71 and 5.05 AE 2.64 months, respectively. Conclusion: In patients with aPLA2R-associated PMN, reduction in circulating aPLA2R precedes clinical remission. Persistence of aPLA2R at the end of therapy is associated with clinical resistance.
Pathophysiological advances in membranous nephropathy: time for a shift in patient's care
The Lancet, 2015
Membranous nephropathy is a major cause of nephrotic syndrome of non-diabetic origin in adults. It is the second or third leading cause of end-stage renal disease in patients with primary glomerulonephritis, and is the leading glomerulopathy that recurs after kidney transplantation (occurring in about 40% of patients). Treatment with costly and potentially toxic drugs remains controversial and challenging, partly because of insuffi cient insight into the pathogenesis of the disease and absence of sensitive biomarkers of disease activity. The disease is caused by the formation of immune deposits on the outer aspect of the glomerular basement membrane, which contain podocyte or planted antigens and circulating antibodies specifi c to those antigens, resulting in complement activation. In 2002, podocyte neutral endopeptidase was identifi ed as an antigenic target of circulating antibodies in alloimmune neonatal nephropathy, and in 2009, podocyte phospholipase A 2 receptor (PLA 2 R) was reported as an antigenic target in autoimmune adult membranous nephropathy. These major breakthroughs were translated to clinical practice very quickly. Measurement of anti-PLA 2 R antibodies in serum and detection of PLA 2 R antigen in glomerular deposits can now be done routinely. Anti-PLA 2 R antibodies have high specifi city (close to 100%), sensitivity (70-80%), and predictive value. PLA 2 R detection in immune deposits allows for retrospective diagnosis of PLA 2 R-related membranous nephropathy in archival kidney biopsies. These tests already have a major eff ect on diagnosis and monitoring of treatment, including after transplantation.