Phospholipase A2 Receptor Antibody Research Articles

Analysis of glomerular PLA2R efficacy in evaluating the prognosis of idiopathic membranous nephropathy in the background of different serum anti-PLA2R levels

Objective To verify glomerular PLA2R antigen and serum PLA2R antibody expression in membranous nephropathy as well as to explore glomerular PLA2R efficacy in evaluating the prognosis of idiopathic membranous nephropathy (IMN) in the background of different serum anti-PLA2R levels. Methods We retrospectively analyzed 155 patients who were diagnosed with IMN by kidney biopsy. Patients were divided into six groups according to their serum PLA2R antibody or glomerular PLA2R antigen positiveness and the level of serum anti-PLA2R titer. Both clinical features and pathological characteristics were recorded, and the remission time was compared among groups. Correlation between clinical figures and the anti-PLA2R titer or semi-quantity of glomerular PLA2R antigen was detected. Results A positive correlation between time to partial remission and serum anti-PLA2R titer was found. Among patients with serum anti-PLA2R titer <150 RU/ml, there were shorter remission time in negative glomerular PLA2R antigen group compared with positive glomerular PLA2R antigen, and a positive correlation between time to complete remission and semi-quantity of glomerular PLA2R antigen was found. Conclusion Both glomerular PLA2R antigen and serum anti-PLA2R play a role in disease presentation and prognosis in primary membranous nephropathy. Glomerular PLA2R antigen has a major role on disease prognosis when serum anti-PLA2R titer is less than 150RU/ml, while serum anti-PLA2R has predominant role in IMN prognosis when serum anti-PLA2R titer is above 150RU/ml.

A Case of Membranous Nephropathy Hypothesized to be Associated With COVID-19 Vaccine

A 56-year-old male patient with a medical history of essential hypertension was referred to the emergency room after he was found to have a serum creatinine level of 13 mg/dL at his primary care physician’s office. The patient reported that he had developed a coronavirus disease 2019 (COVID-19)-like infection six months prior that was not confirmed. Two months later, he started to notice dyspnea on exertion and bilateral lower limb swelling and was started on furosemide. He received the first dose of the Moderna COVID-19 vaccine a month before the presentation but did not receive the second dose. Subsequently, his lower limb swelling and exertional dyspnea started worsening. He denied any new medication, dysuria, oliguria, hematuria, fever, or any other symptoms. Initial evaluation was consistent with kidney failure. Hypocalcemia and hyperphosphatemia were noted, along with medical renal disease on renal ultrasound. Eosinophils and nephrotic-range proteinuria were found in the urine. His serum phospholipase A2 receptor (PLA2R) antibodies were positive. A renal biopsy showed membranous glomerulonephritis with moderate segmental sclerosis, as well as tubulointerstitial fibrosis with neutrophils, consistent with acute interstitial nephritis. Positive staining for PLA2R in the glomerular deposits suggested primary membranous nephropathy (MN). He was treated with prednisone first, and when the kidney biopsy was conclusive for membranous glomerulopathy, he was started on rituximab. On admission, he received hemodialysis intermittently, but this was stopped a month after discharge as his renal function normalized. Recently, there have been numerous cases reported with new onset of glomerular disease after receiving the COVID-19 vaccine. Further studies of vaccinated patients are needed to determine whether the severe acute respiratory syndrome coronavirus 2 virus vaccination is associated with a higher risk of MN and to identify potential predisposing factors and mechanisms of kidney injury in patients in whom it occurs.

Serum Protein Signatures Using Aptamer-Based Proteomics for Minimal Change Disease and Membranous Nephropathy

IntroductionMinimal change disease (MCD) and membranous nephropathy (MN) are glomerular diseases (glomerulonephritis [GN]) that present with the nephrotic syndrome. Although circulating PLA2R antibodies have been validated as a biomarker for MN, the diagnosis of MCD and PLA2R-negative MN still relies on the results of kidney biopsy or empirical corticosteroids in children. We aimed to identify serum protein biomarker signatures associated with MCD and MN pathogenesis using aptamer-based proteomics.MethodsQuantitative SOMAscan proteomics was applied to the serum of adult patients with MCD (n = 15) and MN (n = 37) and healthy controls (n = 20). Associations between the 1305 proteins detected with SOMAscan were assessed using multiple statistical tests, expression pattern analysis, and systems biology analysis.ResultsA total of 208 and 244 proteins were identified that differentiated MCD and MN, respectively, with high statistical significance from the healthy controls (Benjamin-Hochberg [BH] P < 0.0001). There were 157 proteins that discriminated MN from MCD (BH P < 0.05). In MCD, 65 proteins were differentially expressed as compared with MN and healthy controls. When compared with MCD and healthy controls, 44 discriminatory proteins were specifically linked to MN. Systems biology analysis of these signatures identified cell death and inflammation as key pathways differentiating MN from MCD and healthy controls. Dysregulation of fatty acid metabolism pathways was confirmed in both MN and MCD as compared with the healthy subjects.ConclusionSOMAscan represents a promising proteomic platform for biomarker development in GN. Validation of a greater number of discovery biomarkers in larger patient cohorts is needed before these data can be translated for clinical care.

Membranous Glomerulonephritis With Positive Serum PLA2R Antibodies: A Case Report Of Replacing Membranous Nephropathy, Massive Proteinuria Despite Immunosuppressive Therapies

Membranous nephropathy (MN) is among the most common causes of nephrotic syndrome in non-diabetic adults, accounting for up to one-third of biopsied cases of nephrotic syndrome. The term MN reflects the primary histologic change noted on light microscopy: glomerular basement membrane (GBM) thickening with little or no cellular proliferation or infiltration MN is most often primary (previously called idiopathic), although it has been associated with hepatitis B antigene, autoimmune diseases, thyroiditis, malignancies (1,2). This case has been reported as its rarely encountered in our clinical practice. Its progression is worsened despite immunosuppressive treatment. The case of male patients with primary membranous nephropathy is presented. He was three years. Still, the nephrosis recurred with massive proteinuria (19180 mg/day) in treated corticosteroid and cyclosporine after conservative therapy had failed and went into remission for addition to weight loss without. Keywords: Membranous Glomerulonephritis, Therapies, Prognosis, Malignancy, Positive serum PLA2R antibodies

New Insights into the Treatment of Glomerular Diseases: When Mechanisms Become Vivid.

Treatment for glomerular diseases has been extrapolated from the experience of other autoimmune disorders while the underlying pathogenic mechanisms were still not well understood. As the classification of glomerular diseases was based on patterns of juries instead of mechanisms, treatments were typically the art of try and error. With the advancement of molecular biology, the role of the immune agent in glomerular diseases is becoming more evident. The four-hit theory based on the discovery of gd-IgA1 gives a more transparent outline of the pathogenesis of IgA nephropathy (IgAN), and dysregulation of Treg plays a crucial role in the pathogenesis of minimal change disease (MCD). An epoch-making breakthrough is the discovery of PLA2R antibodies in the primary membranous nephropathy (pMN). This is the first biomarker applied for precision medicine in kidney disease. Understanding the immune system’s role in glomerular diseases allows the use of various immunosuppressants or other novel treatments, such as complement inhibitors, to treat glomerular diseases more reasonable. In this era of advocating personalized medicine, it is inevitable to develop precision medicine with mechanism-based novel biomarkers and novel therapies in kidney disease.

POS-897 A CASE OF DE NOVO NELL-1 MEMBRANOUS NEPHROPATHY POST COVID-19 VACCINATION

COVID-19 pandemic has upended our lives in ways that we had never imagined. Healthcare providers are learning more about the disease process and its effects both in short-and long-term as the available data is evolving. We as nephrologists have been in unique position since we take care of these patients in multiple settings ranging from intensive care units to our clinics and dialysis units. With more recent data, there have been reports of COVID-19 vaccinations causing de novo or recurrence of glomerulonephritis. We present a case of de novo NELL-1 (Neural epidermal growth factor-like 1) Membranous nephropathy developing after second dose of COVID-19 vaccination (Pfizer-BioNTech) followed by spontaneous remission. 50-year-old female with no past medical history, no prescription or over the counter medication, non-smoker, non-contributory family history was referred to nephrology clinic for evaluation of new onset edema and proteinuria. Age-appropriate cancer screening was negative for any malignancy. Examination was benign except for bilateral upper and lower extremity edema. Laboratory parameters showed normal renal function with creatinine 0.69 mg/dl (0.59-1.04 mg/dl). Urinalysis was without hematuria or pyuria. She had proteinuria at 8,720 mg/g (<180 mg/g) on random estimation, 6,458 mg/day on 24-hour collection with accompanying dyslipidemia and normal serum albumin at 3.5 g/dl (3.5-5 g/dl). Serological testing was negative for lupus, hepatitis B, hepatitis C, monoclonal paraproteins, phospholipase A2 receptor antibody (PLA2R), thrombospondin type 1 domain containing 7A antibody (THSD7A), human immunodeficiency virus and had normal complement i.e., C3 and C4 levels. She had received her second dose of COVID-19 vaccination (Pfizer-BioNTech) approximately 8 weeks prior to clinical evaluation and her symptoms started around 5 weeks after vaccination. Kidney biopsy was consistent with Membranous nephropathy, PLA2R negative, THSD7A negative, NELL-1 positive (Figure 1). Based on the clinical presentation, there was concern if new onset membranous nephropathy is somehow related to COVID-19 vaccination. It was decided to manage patient conservatively without any immunosuppressive therapy. Angiotensin converting enzyme inhibitors were prescribed but had to be discontinued because of hypotension. Patient did have spontaneous clinical remission and her proteinuria improved at 370 mg/g at 4 months after initial clinical presentation and kidney function continued to be normal. Our patient did not have any underlying risk factors for membranous nephropathy. Considering the timeline of COVID-19 Vaccination and development of proteinuria, it does point towards vaccination likely mounting a polyclonal antibody response precipitating NELL-1 + membranous nephropathy which went into spontaneous clinical remission as the vaccination effect waned. Though, based on this causality cannot be proven. At this point, we are still contemplating whether our patient should get third booster or not.

POS-486 SECONDARY POLYCYTHEMIA IN NEPHROTIC SYNDROME – AN UNCOMMON ASSOCIATION

Polycythaemia is defined as haemoglobin (Hb) of over16.5 g/dL in men and 16 g/dL in women or haematocrit of over 49% in men and 48% in women (WHO 2017). Primary polycythaemiais caused by erythropoietin (EPO) receptor mutations or Janus Kinase 2 (JAK2) mutations. Secondary polycythaemia is occasionally seen with renal diseases such as cystic kidney disease, tumours, renal artery stenosis and after renal transplantation. Polycythaemia associated with Nephrotic Syndrome (NS) is very rare. This association was first described by Emmanuel DA and Wenzel FJ in 1962. Here, we describe four patients with NS who had polycythaemia at presentation.Heavy protienuria leading to renal interstitial oedema causing hypoxia and increased EPO production and high serum IL8 and increased stability of IL8 mRNA(in minimal change disease) are thought to cause secondary polycythaemia in NS. The resolution of polycythaemia following reduction in proteinuria further strengthens the causation.The exact pathogenesis remains to be elucidated. This is a retrospective observational study conducted in NU Hospitals, Bengaluru, India.There were four patients with NS and polycythaemia, between February 2015 to May 2021. All patients with NSwere subjected to biochemical investigations and ultrasonography (USG) of the abdomen after a detailed history and physical examination as per our hospital protocol. Coagulation profile and blood grouping were done prior to renal biopsy. Percutaneous renal biopsy was done under real-time USG guidance. The tissue obtained was sent for Light microscopic examination, Immunofluorescence microscopy and Electron microscopy. In view of the polycythaemia, all these patients underwent a Chest X Ray, arterial blood gas (ABG) analysis, serum EPO and serum JAK2 mutation studies. All four patients in our study were men. Mean age was 32.25 ± 11.70 years. Mean Hb was 18.75 ± 1.22 g/dL. Mean hematocrit was 54.67 ± 6.5 %. Mean proteinuria at onset was 7.62 ± 7.45 grams/day. Mean serum creatinine at the onset was 1.30 ± 0.58 mg/dL. None had splenomegaly. All had normal total white cell and platelet count. None were smokers. ABG was normal in all. All patients had normal serum EPO levels (mean 3.4±1.64 mU/ml) and negative JAK2 mutation analysis. The etiology of NS was minimal change disease (MCD), primary membranous nephropathy (MGN), primary focal segmental glomerulosclerosis (FSGS) and IgA nephropathy in each one of them. PLA2R antibodies were positive in the serum and renal tissue of the patient with MGN.Immunosuppression was initiated in all patients except the patient with IgA nephropathy who had significant chronicity. Three out of four patients had resolution of polycythemia in parallel with remission of NS.The patient with MCD was detected to have polycythaemia during a relapse. This study highlights polycythaemia as an unusual complication of NS.Most cases of NS and polycythemia documented in the literature correspond to FSGS, mainly associated with polycythaemia vera. There are case reports of secondary polycythaemia associated with primary FSGS, MGN and MCD. We didn't do IL8 and IL11 assay in our patients. To the best of our knowledge ours is probably the largest case series of polycythaemia associated with NS.

Evaluation of efficacy of rituximab for membranous nephropathy: A systematic review and meta-analysis of 11 studies

IntroductionThe use of traditional immunosuppressive medicines for the treatment of membranous nephropathy is being challenged, owing to its limited efficacy and tolerability. Research on M-type phospholipase A2 receptor antibodies has provided a new way for evaluating the efficiency and prognosis of treatment of membranous nephropathy. However, the relationship between rituximab, a monoclonal antibody against CD20, and antiphospholipase A2 receptor antibodies and the drug regimen of rituximab for membranous nephropathy is uncertain. We conducted a meta-analysis to evaluate the efficacy of rituximab treatments in membranous nephropathy and compared the clinical effects of first-line and second-line rituximab therapies. MethodsPubMed, Embase, Web of Science, Scopus, the Cochrane Central Register ofControlled Trials, and ClinicalTrials.gov were searched to find articles about rituximab treatment of patients with membranous nephropathy between January 2000 and August 2020. The outcomes included remission, antiphospholipase A2 receptor antibodies, relapse, and adverse events. The Grading of Recommendations Assessment Development and Evaluation criteria were used to evaluate the strength of evidence. ResultsA total of 723 participants from 11 trials were included in this meta-analysis. The other treatments included cyclosporine, cyclophosphamide, steroids, and non-immunosuppressive antiproteinuric treatment. Rituximab significantly improved cumulative remission (P=0.007; Odds Ratio [OR]=3.06; 95% confidence interval [CI]=1.35–6.94) compared with other treatments. It significantly reduced relapse (P<0.00001; OR=0.06; 95% CI=0.02–0.19), antiphospholipase A2 receptor antibody levels (P=0.0009; SMD=−0.52; 95% CI=−0.83 to −0.21), and the proportion of patients positive for anti-PLA2R antibodies (P=0.003; OR=6.11; 95% CI=1.85–20.24) compared with other treatments. Compared with the second-line, first-line rituximab therapy achieved a higher rate of cumulative remission (P=0.03; OR=0.32, 95% CI=0.11–0.91). ConclusionsRituximab can improve the rate of clinical remission in patients with membranous nephropathy. Rituximab was more effective than other treatments in reducing relapse, antiphospholipase A2 receptor antibody levels, and the proportion of patients positive for antiphospholipase A2 receptor antibodies. The clinical remission rate following first-line rituximab therapy was better than that of second-line rituximab therapy for membranous nephropathy.

Efficacy and Safety of Different Immunosuppressive Therapies in Patients With Membranous Nephropathy and High PLA2R Antibody Titer.

Background: This study aimed to evaluate clinical features and prognosis and therapy option of patients with different risk ranks based on antibody against the M-type phospholipase-A2-receptor (PLA2Rab) level in seropositive M-type phospholipase-A2-receptor (PLA2R)-associated membranous nephropathy (MN) in a large sample size, multi-center study. Method: Based on the unvalidated cut-off value of PLA2Rab above 150 RU/ml as one of the clinical criteria for high risk of progressive kidney function loss in MN according to 2020 Kidney Disease: Improving Global Outcomes (KDIGO) draft guidelines recommendation, a total of 447 patients who received cyclophosphamide (CTX) or tacrolimus (TAC) combined with corticosteroids treatment for 12 months were divided into high titer (>150 RU/ml) group and non-high titer (20–150 RU/ml) group, which were subdivided into CTX subgroup and TAC subgroup. The overall cohort was classified into CTX group and TAC group as well. Clinical parameters levels and remission rates were recorded at 3, 6, and 12 months follow-up. PLA2Rab was tested by enzyme-linked immunosorbent assay. Results: Patients with high titer PLA2Rab were associated with more severe proteinuria and hypoalbuminemia compared to those with non-high titer antibody, accompanied by lower complete remission (CR) and total remission (TR) rates at 3, 6, and 12 months, which even took longer to remission. Similar remission rates differences between the two titer groups were observed in the CTX and TAC groups, respectively. PLA2Rab level at baseline was an independent predictive factor for CR and TR. In the high titer group, CR and TR rates in the CTX subgroup were significantly higher than those in the TAC subgroup at 12 months, although serious adverse events were more frequent in the former. Conclusion: High-risk rank patients with PLA2Rab level above 150 RU/ml have higher disease activity and worse prognosis among patients with seropositive PLA2R-associated MN, even under different immunosuppressive therapeutic models; moreover, CTX combined with corticosteroids was preferred compared to TAC plus corticosteroids, although serious adverse events were more frequent in the former. Additionally, baseline PLA2Rab level was an independent predictive factor for clinical remission.

Posttransplant membranous nephropathy - A case report

Primary membranous nephropathy (PMN) is a common cause of adult-onset nephrotic syndrome. Anti-M-type phospholipase A2 receptor (PLA2R) antibodies are pathogenic and correlate with clinical outcomes. The role of anti-PLA2R in recurrent PMN is unclear. In the present manuscript, we report five cases of PMN who underwent kidney transplantation (KT) with varying titers of anti-PLA2R pre-kidney transplantation (KT). Two patients with anti-PLA2R in the second and third tertiles had a recurrence of PMN, whereas patients with a negative or anti-PLA2R in the first tertile had no recurrence. The report signals a heightened risk of PMN recurrence in patients with elevated anti-PLA2R antibody titer at KT.

Anti-phospholipase A2 Receptor Antibody in Differentiation and Prognostication of Membranous Nephropathy.

Anti-M-type phospholipase A2 receptor (anti-PLA2R) antibody is believed to be associated with primary membranous nephropathy (pMN) and absent in secondary MN (sMN). There are few data regarding utility of anti-PLA2R antibody as a prognosticator. Our study aimed to compare the incidence of positive serum anti-PLA2R antibody titer in pMN versus sMN and correlation with clinical outcome. From August 2015 to July 2019, patients with biopsy-proven MN were evaluated for serum anti-PLA2R antibody titers by the enzyme-linked immunosorbent assay. The subset of cases was repeated to monitor the clinical response in terms of 24 h proteinuria. A total of 169 patients, 65 pMN and 104 sMN were studied. Anti-PLA2R antibody was found in 41 (63.08%) pMN with mean titer, 232.62 RU/mL, and 40 (38.46%) sMN with mean titer 253.59 RU/mL. Out of positive antiPLA2R antibody titer in pMN cases, 15 were retested twice to 5 times with mean titers of 78.95, 36.27, 13.9, and 15.45 RU/mL, respectively. Out of positive anti-PLA2R antibody in sMN cases, 11 were retested twice to five times with mean titers of 104.42, 122.49, 12.33, and 17.2 RU/mL, respectively. All patients with decreasing anti-PLA2R antibody titer in both groups had clinical remission, with a decrease in mean 24 h proteinuria from 7.11 g to 3.36 g in pMN and 5.97 g to 3.41 g in sMN. Ten pMN and 11 sMN patients without remission showed persistent positive anti- PLA2R antibody titer. Anti-PLA2R antibody titer may be elevated in pMN/sMN. It can also be used as a noninvasive prognostic marker for MN.

The role of PLA2R antibody monitoring: what we know and what we do not know.

For a long time, kidney biopsy was the only diagnostic means for membranous nephropathy (MN) and proteinuria and serum creatinine were the only markers of disease activity. The discovery of the phospholipase A2 receptor (PLA2R) antibody in 2009 has induced a paradigm shift in both the diagnosis and monitoring of patients. Two serological tests are routinely used: the enzyme-linked immunosorbent assay (ELISA), which is quantitative, and the immunofluorescence assay (IFA), which is more sensitive. In centres where the two assays are available, the recommendation is to use IFA for screening and diagnosis of immunological remission and ELISA for monitoring the effectiveness of therapy. In patients with positive PLA2R antibody serology, normal kidney function and no evidence of an underlying disease, a kidney biopsy is not mandatory given the almost 100% specificity of the assays. Because MN has different phases, one cannot base a clinical or therapeutic decision on a single measurement of PLA2R antibody at baseline. Risk evaluation of disease progression is a dynamic process that should be performed repeatedly to capture the trajectory of the disease based on both the traditional biomarkers (proteinuria and serum creatinine) and PLA2R antibody levels. The effectiveness of therapy is also evaluated on the PLA2R antibody trajectory, particularly during the first 6 months. Finally, PLA2R antibody monitoring has transformed the management of patients with kidney allografts. Future studies are needed to develop more subtle immunological tests, including monitoring of antigen-specific memory B cells.

Rituximab Is Preferable to Cyclophosphamide for Treatment of Membranous Nephropathy: CON.

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0001842021 and the COMMENTARY: 10.34067/KID.0002492021

The correlation between Serum phospholipase A2 receptor antibody and clinicopathological features in patients with membranous nephropathy

Objective: To assess the correlation between Serum phospholipase A2 receptor antibody and clinicopathological features in patients with membranous nephropathy. Method: The patients being hospitalized for renal biopsy were selected in this study from January 2016 to January 2018. And normal controls were randomly selected; all the patients were divided into idiopathic membranous nephropathy and non-idiopathic membranous nephropathy groups; patients with idiopathic membranous nephropathy were divided into three groups, namely stage I, stage II and stage III; using software for statistical analysis. Results: A total of 357 patients were enrolled, including 155 patients with idiopathic membranous nephropathy, 183 patients with non-idiopathic membranous nephropathy, and 19 cases for normal controls. The average age of the idiopathic membranous nephropathy (IMN) group is higher than that of the membranous nephropathy group (P = 0.01). Different pathological stages of idiopathic membranous nephropathy general clinical characteristics analysis results showed that the age, cys c, serum creatinine (Scr) in stage III membranous nephropathy group were higher than those of the stage I and II membranous nephropathy (P values were 0.003, 0.000 and 0.000 respectively); titers of serum phospholipase A2 receptors antibody with stage II and III membranous nephropathy higher than the stage I membranous nephropathy group (P = 0.006); serum albumin (Alb) levels correlated inversely with serum anti-PLA2R antibody titers (rs = –0.234, P = 0.003), serum antiphospholipase A2 receptor (PLA2R) antibody titer level in patients with idiopathic membranous nephropathy was significantly higher than that in patients with non-membranous nephropathy (P &lt; 0.001). Conclusion: Baseline titer of serum anti-PLA2R antibody is negatively correlated with Alb in the IMN patients，and serum anti-PLA2R antibody level in patients with stage I IMN was significantly lower than stage II and III IMN patients.

Kidney injury molecule-1 levels are associated with therapeutic outcomes and renal tubulointerstitial injury severity in idiopathic membranous nephropathy.

Kidney injury molecule-1 (KIM-1) has an important role in chronic kidney disease development. The present study aimed to retrospectively analyze patients with idiopathic membranous nephrology (IMN) with different therapeutic outcomes to investigate the association between KIM-1 levels and therapeutic outcomes. A total of 51 patients with IMN and 20 healthy controls were included. Patients were classified into three groups: Spontaneous remission, remission with immunosuppressive therapy (IST) and nonremission with IST. Clinical and biochemical variables were collected. Urinary KIM-1 levels were measured by ELISA and renal KIM-1 expression was evaluated by immunohistochemistry. Patients with IMN were characterized as having elevated urinary and renal KIM-1 levels compared with those in the controls. Significantly increased urinary and renal KIM-1 levels were observed in the nonremission with IST group compared with those in the spontaneous remission group, and the same trend was observed for the plasma anti-podocyte antigen phospholipase A2 receptor antibody levels. Patients with more severe tubular injury (T2 index) presented with significantly higher urinary and renal KIM-1 levels than those with the T0 index. Urinary and renal KIM-1 levels were positively correlated with blood urea nitrogen, serum creatinine, serum cystatin-C, urinary albumin/creatinine ratio, urinary β2-microglobulin and the renal interstitial fibrosis index, and they were negatively correlated with serum albumin. Furthermore, urinary KIM-1 levels were positively correlated with the renal KIM-1 levels. In conclusion, the measurement of urinary and renal KIM-1 levels may be helpful in guiding medication selection and predicting therapeutic outcomes for patients with IMN.

Membranous nephropathy.

Membranous nephropathy (MN) is a glomerular disease that can occur at all ages. In adults, it is the most frequent cause of nephrotic syndrome. In ~80% of patients, there is no underlying cause of MN (primary MN) and the remaining cases are associated with medications or other diseases such as systemic lupus erythematosus, hepatitis virus infection or malignancies. MN is an autoimmune disease characterized by a thickening of the glomerular capillary walls due to immune complex deposition. Identification of the phospholipase A2 receptor (PLA2R) as the major antigen in adults in 2009 induced a paradigm shift in disease diagnosis and monitoring and several other antigens have since been characterized. Disease outcome is difficult to predict and around one-third of patients will undergo spontaneous remission. In those at high risk of progression, immunosuppressive therapy with cyclophosphamide plus corticosteroids has substantially reduced the need for kidney replacement therapy. Owing to carcinogenic risk, other treatments (calcineurin inhibitors and CD20-targeted B cell depletion therapy (rituximab)) have been developed. However, disease relapses are frequent when calcineurin inhibitors are stopped and the remission rate with rituximab is lower than with cyclophosphamide, particularly in patients with high PLA2R antibody titres. Other new drugs are already available and antigen-specific immunotherapies are being developed.

A case report of breast cancer and membranous nephropathy with positive anti phospholipase A2 receptor antibodies

BackgroundTesting for antibodies against podocyte phospholipase A2 receptor-1 (PLA2R) allows clinicians to accurately identify primary membranous nephropathy (MN). Secondary MN is associated with a spectrum of pathology including solid organ malignancy. PLA2R positivity in these patients occurs, although no case of PLA2R-positive MN has been definitively linked to cancer.Case presentationWe describe a case of biopsy-proven PLA2R-positive MN, in whom invasive ductal carcinoma of the breast was discovered. The patient underwent surgery and adjuvant chemotherapy (including cyclophosphamide) and went into a sustained complete remission of her nephrotic syndrome.Discussion and conclusionsCase series have reported PLA2R positivity in patients with solid organ malignancy associated MN. Our case is unusual as it is a breast malignancy, and the patients nephrotic syndrome and anti-PLA2Rab titres improved with treatment of the cancer. Here we report, to the best of our knowledge, the first case of oestrogen receptor-2 positive breast cancer associated with PLA2R positive MN in a young lady that was treated successfully by treating the malignancy.

A PLA2R-IgG4 Antibody-Based Predictive Model for Assessing Risk Stratification of Idiopathic Membranous Nephropathy.

Background Known as an autoimmune glomerular disease, idiopathic membranous nephropathy (IMN) is considered to be associated with phospholipase A2 receptor (PLA2R) in terms of the main pathogenesis. The quantitative detection of serum PLA2R-IgG and PLA2R-IgG4 antibodies by time-resolved fluoroimmunoassay (TRFIA) was determined, and the value of them, both in the clinical prediction of risk stratification in IMN, was observed in this study. Methods 95 patients with IMN proved by renal biopsy were enrolled, who had tested positive for serum PLA2R antibodies by ELISA, and the quantitative detection of serum PLA2R-IgG and PLA2R-IgG4 antibodies was achieved by TRFIA. All the patients were divided into low-, medium-, and high-risk groups, respectively, which were set as dependent variables, according to proteinuria and renal function. Random forest (RF) was used to estimate the value of serum PLA2R-IgG and PLA2R-IgG4 in predicting the risk stratification of progression in IMN. Results Out-of-bag estimates of variable importance in RF were employed to evaluate the impact of each input variable on the final classification accuracy. The variable of albumin, PLA2R-IgG, and PLA2R-IgG4 had high values (>0.3) of 0.3156, 0.3981, and 0.7682, respectively, which meant that these three were more important for the risk stratification of progression in IMN. In order to further assess the contribution of PLA2R-IgG and PLA2R-IgG4 to the model, we built four different models and found that PLA2R-IgG4 played an important role in improving the predictive ability of the model. Conclusions In this study, we established a random forest model to evaluate the value of serum PLA2R-IgG4 antibodies in predicting risk stratification of IMN. Compared with PLA2R-IgG, PLA2R-IgG4 is a more efficient biomarker in predicting the risk of progression in IMN.

Treatment preferences for primary membranous nephropathy: Results of a multinational survey among nephrologists in the South Asia Pacific region.

There is no clear consensus on how best to treat primary membranous nephropathy (PMN). This study aimed to ascertain prevailing views among nephrologists on their choice of immunosuppressive agents to treat this disease. The Australasian Kidney Trials Network conducted a multinational online survey among nephrologists from the South Asia-Pacific region to identify prescribing practices to treat PMN. Survey questions focused on the types of immunosuppressive therapies used, preferred first-line and second-line therapies, indications for starting immunosuppressive therapy, the preferred mode of combining corticosteroid and cyclophosphamide, the use of serum phospholipase A2 receptor antibody testing in clinical practice, indications for anticoagulation, and interest in participating in future clinical trials in PMN. One hundered fifty-five nephrologists from eight countries responded to the online survey. The majority of them were senior nephrologists from Australia and India with significant experience managing patients with PMN. The combination of cyclophosphamide and corticosteroid was the preferred first-line therapy. Of those who used this combination, only 34.8% followed the Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines by adding intravenous methylprednisolone. The combination of calcineurin inhibitor with corticosteroid was the most common second-line therapy. Most respondents considered prophylactic anticoagulation if serum albumin was less than 25 g/L. Most nephrologists were keen to participate in a clinical trial with a control arm consisting of cyclophosphamide and corticosteroids. The combination of corticosteroid with cyclophosphamide (without intravenous methylprednisolone) is the most commonly reported first-line immunosuppressive therapy for the management of PMN.

Repository Corticotropin Injections Promote Clinical Remission and Regulatory T Cell Expansion in Membranous Nephropathy

Repository Corticotropin Injections Promote Clinical Remission and Regulatory T Cell Expansion in Membranous Nephropathy