scholarly journals Malignancy-Associated Membranous Nephropathy with Positive Anti-PLA2R Autoantibodies: Coincidence or Connection

2021 ◽  
pp. 334-339
Author(s):  
Lyle W. Baker ◽  
Jaime Jimenez-Lopez ◽  
Xochiquetzal J. Geiger ◽  
Nabeel Aslam
Keyword(s):  
Renal Cell Carcinoma ◽  
Nephrotic Syndrome ◽  
Membranous Nephropathy ◽  
High Serum ◽  
Phospholipase A2 Receptor ◽  
Serum Titer ◽  
Current Classification ◽  
Age Appropriate ◽  
Poorly Differentiated ◽  
Very High

Membranous nephropathy (MN) is currently classified as either primary – often associated with positive anti-phospholipase-A2 receptor (PLA2R) autoantibodies – or as secondary – associated with malignancy, infection, medications, or autoimmune disease. We present a case of biopsy-proven MN with very high serum titer of anti-PLA2R autoantibodies in a patient with a synchronous diagnosis of poorly differentiated esophageal adenocarcinoma and renal cell carcinoma who presented with nephrotic syndrome. Based on the current classification, MN in the presence of active malignancy is diagnosed as secondary and unlikely to have positive anti-PLA2R autoantibodies. This raises several questions: whether this patient has secondary MN associated with malignancy and coincidentally discovered anti-PLA2R autoantibodies, primary MN due to anti-PLA2R autoantibodies with coincidentally discovered malignancy, or whether malignancy can induce the formation of anti-PLA2R autoantibodies that result in MN. This case report highlights the importance of age-appropriate cancer screening, even in patients with presumed primary MN and positive anti-PLA2R autoantibodies.

scholarly journals Successful foetal outcome in a patient with primary membranous nephropathy and circulating anti-phospholipid antibodies: A case report

2018 ◽  
Keyword(s):  
Nephrotic Syndrome ◽  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Membranous Glomerulonephritis ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Phospholipase A2 Receptor ◽  
Foetal Outcome ◽  
Circulating Autoantibodies ◽  
Patient’S History

There is little information about pregnancy outcomes in patients with active membranous nephropathy (MN), especially those with circulating autoantibodies to M-type phospholipase A2 receptor (PLA2R), the major autoantigen in primary MN. Membranous glomerulonephritis (MGN) represents an immunologically mediated disease characterized by deposition of immune complexes in the glomerular subepithelial space, frequently associated with circulating M-type phospholipase A2 receptor. Nephrotic syndrome (massive proteinuria and hypoalbuminemia) at diagnosis predicts poor prognosis. Pregnancy with active MGN is high risk for foetal loss, intrauterine growth restriction, and pre-eclampsia, and may worsen maternal renal function, especially with the presence of antiphospholipid antibody syndrome (APLA). We report a 23-year-old gravida in her first pregnancy, suffering from MGN and severe nephrotic syndrome, complicated by APLA syndrome. The patient was treated with enoxaparin, aspirin azathioprine, and Prednisone for a short time, in addition to furosemide and albumin intravenously. She was delivered at 30 weeks due to deteriorating maternal and foetal conditions. A successful neonatal and maternal outcome was achieved in this case. The patient's history revealed thrombocytopenia and APLA syndrome and continues to be treated chronically with enoxaparin. Kidney biopsy performed after delivery showed membranous MGN stage II-III. Herein, we present a case of successful pregnancy and foetal outcome in a young woman with APLA syndrome and MN. Keywords: Membranous GN, Nephrotic Syndrome, Anti-Phospholipid Antibodies.

scholarly journals An Overview of Molecular Mechanism of Nephrotic Syndrome

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Juliana Reis Machado ◽  
Laura Penna Rocha ◽  
Precil Diego Miranda de Menezes Neves ◽  
Eliângela de Castro Cobô ◽  
Marcos Vinícius Silva ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Membranous Nephropathy ◽  
Epithelial Mesenchymal Transition ◽  
Membrane Damage ◽  
Membranous Glomerulonephritis ◽  
Basal Membrane ◽  
Experimental Models ◽  
Mesenchymal Transition ◽  
Disease Occurrence ◽  
Phospholipase A2 Receptor

Podocytopathies (minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS)) together with membranous nephropathy are the main causes of nephrotic syndrome. Some changes on the expression of nephrin, podocin, TGF-β, and slit diaphragm components as well as transcription factors and transmembrane proteins have been demonstrated in podocytopathies. Considering the pathogenesis of proteinuria, some elucidations have been directed towards the involvement of epithelial-mesenchymal transition. Moreover, the usefulness of some markers such as TGF-β1, nephrin, synaptopodin, dystroglycans, and malondialdehyde have been determined in the differentiation between MCD and FSGS. Experimental models and human samples indicated an essential role of autoantibodies in membranous glomerulonephritis, kidney damage, and proteinuria events. Megalin and phospholipase-A2-receptor have been described as antigens responsible for the formation of the subepithelial immune complexes and renal disease occurrence. In addition, the complement system seems to play a key role in basal membrane damage and in the development of proteinuria in membranous nephropathy. This paper focuses on the common molecular changes involved in the development of nephrotic proteinuria.

scholarly journals A novel approach to rapid induction of remission in primary membranous nephropathy

2021 ◽  
Vol 93 (6) ◽  
pp. 706-712
Author(s):  
Vladimir A. Dobronravov ◽  
Olga B. Bystrova ◽  
Zinaida Sh. Kochoyan ◽  
Evgeniya N. Fomicheva
Keyword(s):  
Membranous Nephropathy ◽  
Cumulative Incidence ◽  
Therapy Group ◽  
High Serum ◽  
High Dose ◽  
Control Groups ◽  
Open Label ◽  
Serious Adverse Events ◽  
Rapid Induction ◽  
Phospholipase A2 Receptor

Aim. То evaluate the effectiveness of a novel multi-targeted treatment approach including rituximab (RTX), cyclophosphamide (CPH) and steroids (S) to the induction of remission in patients with primary membranous nephropathy (PMN) compared to standard immunosuppression (IST). Materials and methods. An open-label prospective comparative study included 56 PMN patients (pts) with nephrotic syndrome (NS) and high serum level of antibodies to the phospholipase A2 receptor anti-PLA2R (mean age 5112 years, men 70%). We recorded demographic and clinical parameters at the time of kidney biopsy, data from light-optical and immunomorphological studies. All pts were on stable doses of the renin-angiotensin systems blockers. We compared the effectiveness of different treatments in the inductions of clinical and immunological remissions in pts who received experimental treatment with RTX, CPH and S (RTX+CPH+S group, n=14) and two control groups: high-dose RTX therapy (group RTX, n=12), cyclosporine and steroids (group CsA+S, n=30). Results. In the RTX+CPH+S group, remission was achieved in 100% of cases (of which complete remissions CR in 21.4%). The median time-to-remission (2.5 [1.0; 3.5] months) was significantly lower compared to both control groups: RTX (8.7 [6.6; 14.0] months, p=0.005) and CsA+S (12.4 [6.5; 19.9] months, p0.001). The cumulative incidence of clinical and immunological remissions was also significantly higher in the RTX+CPH+S group than in the control groups. These results were confirmed in comparative analyzes in the same treatment groups after propensity score matching. The cumulative incidence of clinical and immunological remissions in the RTX+CPH+S group was higher than in the combined group of patients who received other therapies (p0.001). The incidence of serious adverse events was low and did not differ between groups. Conclusion. The use of multi-targeted therapy with rituximab, cyclophosphamide, and steroids seems to be an effective approach for the rapid induction of PMN remission and prevention of NS complications.

The Prevalence of Mesangial Electron-Dense Deposits in PLA2R-Positive Membranous Nephropathy

Nephron ◽  
2021 ◽  
pp. 1-5
Author(s):  
Gabriel Giannini ◽  
Lois J. Arend
Keyword(s):  
Electron Microscopy ◽  
Nephrotic Syndrome ◽  
Membranous Nephropathy ◽  
Immunofluorescence Microscopy ◽  
Common Cause ◽  
Electron Dense Deposit ◽  
Dense Deposit ◽  
Phospholipase A2 Receptor ◽  
Dense Deposits ◽  
Negative Biopsies

<b><i>Introduction:</i></b> Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults and can be primary or secondary. The antigenic target of antibodies in 70% of primary cases is phospholipase A2 receptor (PLA2R). The presence or absence of mesangial electron-dense deposits has been used to distinguish between primary and secondary MN. Mesangial deposits suggest MN due to lupus, infection, or other causes, though they are reported to occur in approximately 10% of primary MN. Staining for PLA2R is now frequently used for confirming a diagnosis of primary MN. If mesangial deposits predict a secondary cause, they should be more frequent in PLA2R-negative biopsies. <b><i>Methods:</i></b> A review of institutional kidney biopsies between March 2017 and June 2020 identified all cases of MN. Cases with a diagnosis of lupus or near “full-house” staining by immunofluorescence microscopy (IF) were excluded. Light microscopy, IF, and electron microscopy (EM) were performed. PLA2R staining was performed by IF. EM for all cases was reviewed and electron-dense deposit location, distribution, and size were determined. <b><i>Results:</i></b> Ninety-three cases of MN were identified, of which 86 had both PLA2R staining and EM performed. Of these, 51 cases (59%) were positive for PLA2R and 35 (41%) were negative. Mesangial electron-dense deposits were present in 22 (25.6%) of the 86 cases, including 27.5% (14/51) of PLA2R-positive cases and 22.8% (8/35) of PLA2R-negative cases. No difference was seen in size or distribution of deposits, or other features considered suggestive of secondary MN. <b><i>Conclusion:</i></b> PLA2R-negative cases were not more likely to have mesangial deposits than PLA2R-positive cases. Mesangial deposits should not be used as an indicator of secondary MN.

Membranous Nephropathy with Lambda Light Chain Restriction: A Rare Form with Serum Negative and Tissue Positive PLA2R Ab

Nephron ◽  
2021 ◽  
pp. 1-4
Author(s):  
Emel Isiktas Sayilar ◽  
Saba Kiremitci ◽  
Ihsan Ergun ◽  
Arzu Ensari
Keyword(s):  
Nephrotic Syndrome ◽  
Light Chain ◽  
Membranous Nephropathy ◽  
Capillary Wall ◽  
Glomerular Capillary Wall ◽  
Glomerular Capillary ◽  
Phospholipase A2 Receptor ◽  
Antibody Positivity ◽  
Immunoglobulin Deposits ◽  
Light Chain Deposition

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. Subepithelial polyclonal immunoglobulin deposits and &#x3e;70% M-type phospholipase A2 receptor antibody positivity are typical findings in idiopathic MN. A 58-year-old female patient was admitted with clinical presentation of nephrotic syndrome. Autoimmune diseases, infections, and malignancies were ruled out after clinical and laboratory evaluations. Diagnostic work-up revealed serum PLA2R antibody negativity and diffuse thickening of glomerular capillary wall on biopsy, while glomerular capillary wall IgG, C3, and Lambda monotypic light chain deposition and PLA2R1 positivity were detected by immunofluorescence and immunohistochemical examination, respectively. Following prednisolone treatment, creatinine and proteinuria were markedly regressed. The MN cases with a light chain deposits are rare and experience regarding their treatment are insufficient.

Nephrotic syndrome as a result of membranous nephropathy caused by renal cell carcinoma

2004 ◽  
Vol 11 (4) ◽  
pp. 235-238 ◽  
Author(s):  
ISAO KURODA ◽  
MUNEHISA UENO ◽  
HIROKAZU OKADA ◽  
SHIHO SHIMADA ◽  
MASUMI AKITA ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Nephrotic Syndrome ◽  
Cell Carcinoma ◽  
Membranous Nephropathy ◽  
Renal Cell

scholarly journals Lupus Membranous Nephropathy

2021 ◽  
Vol 1 (1) ◽  
pp. 10-20
Author(s):  
Claudio Ponticelli ◽  
Gabriella Moroni ◽  
Alessia Fornoni
Keyword(s):  
Nephrotic Syndrome ◽  
Lupus Nephritis ◽  
Membranous Nephropathy ◽  
Calcineurin Inhibitors ◽  
Vitamin D Supplementation ◽  
Ckd Progression ◽  
Frequent Use ◽  
Phospholipase A2 Receptor ◽  
Life Threatening ◽  
Inflammatory Milieu

Background: Lupus membranous nephropathy (LMN) is a rare disease, usually associated with nephrotic syndrome. Methods: We reviewed the literature by searching for the following terms on Pubmed.gov: lupus nephritis, membranous nephropathy (MN), lupus membranous nephropathy, nephrotic syndrome, and Class V lupus nephritis. Results: The histology of LMN at light microscopy is similar to that of primary MN. Cases of MN associated with focal or diffuse proliferation are not considered LMN by the International Society of Nephrology/Renal Pathology Society classification. Immunofluorescence study of LMN shows deposits of all immunoglobulins and complement. Tubulo-reticular structures, extraglomerular deposits, subepithelial, and scanty subendothelial deposits can be seen on electron microscopy. Phospholipase A2 receptor deposits are usually but not necessarily absent in LMN. The pathogenesis is still not completely understood. The inflammatory milieu of lupus may favor the development of autoantigens and intraglomerular assembly of immune complexes. These are more often associated with mesangial or endocapillary hypercellular lesions. Alternatively, autoantibodies may bind autoantigens in the glomerular subepithelium, triggering a signaling cascade leading to LMN. A central role in the development of podocyte injury and proteinuria is played by the components of complement C5b-C9. CKD progression in LMN is slow but may be accelerated by the frequency of renal flares. Persistent nephrotic syndrome and/or the frequent use of corticosteroids may lead to a series of life-threatening complications. Discussion: Treatment of arterial hypertension, dyslipidemia, and diabetes are of paramount importance. Besides specific therapies of these complications, hydroxychloroquine and vitamin D supplementation are recommended. Immunosuppression should be limited to patients with nephrotic proteinuria. The most frequently used drugs are corticosteroids, calcineurin inhibitors, cyclophosphamide, mycophenolate, and rituximab, alone or combined. Early detection and treatment of renal flares is of paramount importance to prevent CKD progression.

scholarly journals Case Report: A Rare Presentation of NSAID-Induced Secondary Membranous Nephropathy in a Pediatric Patient

2021 ◽  
Vol 9 ◽  
Author(s):  
Siddharth Shah ◽  
M. Asope Elder ◽  
Jessica Hata
Keyword(s):  
Nephrotic Syndrome ◽  
Renal Biopsy ◽  
Membranous Nephropathy ◽  
Ace Inhibitor ◽  
Clinical Presentation ◽  
Pediatric Population ◽  
Lower Abdominal Pain ◽  
Rare Presentation ◽  
Phospholipase A2 Receptor ◽  
Secondary Membranous Nephropathy

Background: Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults, but it is responsible for &lt;5% of nephrotic syndrome cases in children. MN has primary and secondary forms. Secondary MN is caused by viral infections, autoimmune diseases like lupus, or drugs. Non-steroid anti-inflammatory drug (NSAID)-induced secondary MN is rarely described in the pediatric population. Thus, the clinical presentation and time to recovery are vastly unknown in the pediatric subgroup.Clinical Presentation: We report a case of a 15-year-old female who presented with acute onset of nephrotic range proteinuria, significant hypoalbuminemia, hyperlipidemia, and lower extremity edema related to the presence of nephrotic syndrome. She had a history of ibuprofen use periodically for 6 months before presentation because of menstrual cramps and intermittent lower abdominal pain. After the presentation, we performed a renal biopsy that reported stage 1–2 MN, likely secondary. The phospholipase A2 receptor (PLA2R) antibody on the blood test and PLA2R immune stain on the renal biopsy sample were negative. We performed a comprehensive evaluation of the viral and immune causes of secondary MN, which was non-revealing. She had stopped ibuprofen use subsequent to the initial presentation. She was prescribed ACE inhibitor therapy. After 6 months of ACE inhibitor treatment, the proteinuria had resolved.Conclusion: Proteinuria can last for several weeks when NSAID induces secondary MN and nephrotic syndrome. With the widespread use of NSAIDs prevalent in the pediatric community, further studies are needed to evaluate and study the role of NSAIDs in this condition.

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