A Refractory Case of Secondary Membranous Nephropathy Concurrent with IgG4-related Tubulointerstitial Nephritis

Immunoglobulin G4-related disease (IgG4-RD) has recently been recognized as an autoimmune disorder involving multiple organs. The kidney is a represented organ with a wide range of renal manifestations. The authors report a case of an 83-year-old Thai male with combined IgG4 tubulointerstitial nephritis and membranous nephropathy coexisting with cholangiocarcinoma. The patient presented with proteinuria, acute renal failure, eosinophilia, hypocomplementemia, and high serum IgG4 concentration. The diagnosis was IgG 4-related tubulointerstitial nephritis and membranous nephropathy on renal biopsy, with negative immunohistochemistry for anti-phospholipase A2 receptor antibodies. Magnetic resonance imaging (MRI) abdomen showed two wedge shaped arterial enhancing lesions of liver. Liver biopsy revealed adenocarcinoma, compatible with cholangiocarcinoma. Proteinuria and renal failure were resolved with initial steroid treatment. Meanwhile, IgG4-related membranous nephropathy should be considered in the differential diagnosis for patients with proteinuria. Potentially, IgG4-RD may be rarely associated with carcinoma development. However, further studies are recommended to ratify and confirm the association between IgG4-RD and incidence of malignancies. Keywords: IgG4-related disease, Membranous nephropathy, Secondary membranous nephropathy, Tubulointerstitial nephritis, Cholangiocarcinoma

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Membranous nephropathy associated with multicentric Castleman’s disease that was successfully treated with tocilizumab: a case report and review of the literature

BMC Nephrology ◽

10.1186/s12882-021-02423-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ryosuke Saiki ◽

Kan Katayama ◽

Yosuke Hirabayashi ◽

Keiko Oda ◽

Mika Fujimoto ◽

...

Keyword(s):

Membranous Nephropathy ◽

Periodic Acid ◽

Castleman’S Disease ◽

Basement Membranes ◽

The Body ◽

Castleman's Disease ◽

Multicentric Castleman’S Disease ◽

High Zinc ◽

Secondary Membranous Nephropathy ◽

Multicentric Castleman's Disease

Abstract Background Multicentric Castleman’s disease is a life-threatening disorder involving a systemic inflammatory response and multiple organ failure caused by the overproduction of interleukin-6. Although renal complications of Castleman’s disease include AA amyloidosis, thrombotic microangiopathy, and membranoproliferative glomerulonephritis, membranous nephropathy is relatively rare. We experienced a case of secondary membranous nephropathy associated with Castleman’s disease. Case presentation The patient was a 43-year-old Japanese man who had shown a high zinc sulfate value in turbidity test, polyclonal hypergammaglobulinemia, anemia, and proteinuria. A physical examination revealed diffuse lymphadenopathy, an enlarged spleen and papulae of the body trunk. A skin biopsy of a papule on the patient’s back showed plasma cells in the perivascular area and he was diagnosed with multicentric Castleman’s disease, plasma cell variant. Kidney biopsy showed the appearance of bubbling in the glomerular basement membranes in Periodic acid methenamine silver stain and electron microscopy revealed electron dense deposits within and outside the glomerular basement membranes. Since immunofluorescence study showed predominant granular deposition of IgG1 and IgG2, he was diagnosed with secondary membranous nephropathy associated with Castleman’s disease. He was initially treated with prednisolone alone, however his biochemical abnormalities did not improve. After intravenous tocilizumab (700 mg every 2 weeks) was started, his C-reactive protein elevation, anemia, and polyclonal gammopathy improved. Furthermore, his urinary protein level declined from 1.58 g/gCr to 0.13 g/gCr. The prednisolone dose was gradually tapered, then discontinued. He has been stable without a recurrence of proteinuria for more than 6 months. Conclusions Tocilizumab might be a treatment option for secondary membranous nephropathy associated with Castleman’s disease.

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Membranous Nephropathy with Glomerular IgG4 Deposition Without Tubulointerstitial Nephritis in a Patient with Typical IgG4-Related Pancreatic, Hepatic, and Lymph Node Lesions

IgG4-Related Disease ◽

10.1007/978-4-431-54228-5_32 ◽

2013 ◽

pp. 225-229

Author(s):

Kazuhiro Hatta

Keyword(s):

Lymph Node ◽

Membranous Nephropathy ◽

Tubulointerstitial Nephritis

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Membranous glomerulonephritis

10.1093/med/9780199592548.003.0061_update_001 ◽

2018 ◽

Author(s):

Daniel C. Cattran ◽

Heather N. Reich

Keyword(s):

Nephrotic Syndrome ◽

Hepatitis B ◽

Renal Biopsy ◽

Clinical Picture ◽

Membranous Nephropathy ◽

Membranous Glomerulonephritis ◽

Hepatitis B Infection ◽

Immunoglobulin G4 ◽

Secondary Membranous Nephropathy ◽

Secondary Causes

Membranous glomerulonephritis (MGN) usually presents as nephrotic syndrome, which may be severe. It is primarily a disease of adults, men more than women, with a peak incidence in the fourth and fifth decades. It is hoped that proven tests for the characteristic anti-PLA2R antibodies of primary MGN may become established, but the diagnosis currently rests on renal biopsy showing characteristic subepithelial granular immune deposits. These usually contain immunoglobulin G4 and complement. Other patterns may suggest secondary causes of MGN. Secondary membranous nephropathy occurs in lupus and some other immune or autoimmune disorders, in hepatitis B infection, after exposure to some drugs or toxins, and in some cancers. Secondary causes are more common at extremes of age, and are often made obvious by the history or clinical picture. How hard to look for malignancy is controversial, but malignancy is much more likely in patients over 60 years, and may be apparent at presentation.

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Membranous glomerulonephritis

10.1093/med/9780199592548.003.0060_update_001 ◽

2018 ◽

Author(s):

Daniel C. Cattran ◽

Heather N. Reich

Keyword(s):

Membranous Nephropathy ◽

Adult Life ◽

Membranous Glomerulonephritis ◽

Adult Onset ◽

Common Cause ◽

End Stage Renal Failure ◽

Surface Molecules ◽

Phospholipase A2 Receptor ◽

Secondary Membranous Nephropathy ◽

End Stage

Membranous glomerulonephritis (MGN) is the most common cause of adult-onset nephrotic syndrome, and a common glomerular cause of end-stage renal failure. It is caused by antibodies to podocyte surface molecules, usually autoantibodies. In most patients with primary membranous nephropathy the target is the phospholipase A2 receptor. It is hoped that robust assays for this antibody will help to guide therapy but it has not been possible to test this adequately yet. Primary MGN accounts for about 70% of cases with regional variations. MGN is more common in men than women (approximately 2:1) and its peak incidence is in middle adult life. Secondary membranous nephropathy occurs in lupus and some other immune or autoimmune disorders, in hepatitis B infection, after exposure to some drugs or toxins, and in some cancers.

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PLA2R-Negative Membranous Nephropathy Presenting as a Prodrome of IgG4-Related Autoimmune Pancreatitis

Case Reports in Nephrology and Dialysis ◽

10.1159/000501260 ◽

2019 ◽

Vol 9 (2) ◽

pp. 85-91

Author(s):

Magdalini Velegraki ◽

Kostas G. Stylianou ◽

Dimitrios Xydakis ◽

Hariklia Gakiopoulou ◽

Evangelos Voudoukis ◽

...

Keyword(s):

Diabetes Mellitus ◽

Autoimmune Pancreatitis ◽

Membranous Nephropathy ◽

Tubulointerstitial Nephritis ◽

Pathological Feature ◽

Immunoglobulin G4 ◽

Related Disease ◽

Igg4 Related Disease ◽

Phospholipase A2 Receptor ◽

History Of

Membranous nephropathy (MN) with tubulointerstitial nephritis (TIN) is an established manifestation of immunoglobulin G4 (IgG4)-related disease (IgG4-RD). A pathological feature aiming to distinguish between primary and secondary MN is the presence or absence of glomerular staining for phospholipase A2 receptor (PLA2R), respectively. Isolated MN without TIN has been rarely reported in the context of IgG4-RD. This case report describes a patient with a history of MN successfully treated with steroids and cyclophosphamide, who, 3 years later, presented with unexplained exacerbation of diabetes mellitus due to IgG4-related autoimmune pancreatitis. Pancreatitis was treated, and diabetes improved after treatment with steroids. Based on the presence of isolated IgG4 glomerular capillary deposits along with negative staining for PLA2R and the metachronous appearance of autoimmune pancreatitis, MN was retrospectively classified as secondary to IgG4-RD. Isolated IgG4-positive/PLA2R-negative MN without TIN can be a prodrome of IgG4-RD, reminiscent of MN secondary to neoplasms.

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Serum Antibody and Glomerular Antigen of Antiphospholipase A2 Receptor in Chinese Patients with Idiopathic Membranous Nephropathy

BioMed Research International ◽

10.1155/2020/1693710 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Qiu-hua Zhang ◽

Mian Wu ◽

Zhi-gang Hu ◽

Xiao-bin Liu ◽

Biao Huang ◽

...

Keyword(s):

Renal Function ◽

Serum Creatinine ◽

Serum Albumin ◽

Membranous Nephropathy ◽

Serum Antibody ◽

Chinese Patients ◽

Idiopathic Membranous Nephropathy ◽

Phospholipase A2 Receptor ◽

Secondary Membranous Nephropathy ◽

Clinical Correlations

Background. M-type phospholipase A2 receptor (PLA2R) is the first autoantigen responsible for idiopathic membranous nephropathy (IMN). However, serum PLA2R antibody (PLA2R-Ab) can be inaccurate in distinguishing between IMN and secondary membranous nephropathy, while renal PLA2R antigen (PLA2R-Ag) emerges as an ancillary diagnostic. The present study is aimed at examining the associations between PLA2R-Ab in sera and PLA2R-Ag in kidneys in IMN patients. Methods. A total of 93 patients with IMN were retrospectively identified. Their serum PLA2R-Ab and renal PLA2R-Ag expression levels were determined, and the clinical correlations between these parameters and clinical features were examined. Results. The sensitivities of serum PLA2R-Ab and renal PLA2R-Ag for diagnosing IMN were 74.2% and 88.2%, respectively (P<0.001), with poor consistency. Higher serum PLA2R-Ab levels were correlated to stronger renal PLA2R-Ag expression (P=0.048). Patients with positive PLA2R-Ab significantly differed from those with negative levels, in terms of proteinuric levels over 24 hours (4.54 vs. 3.46 g/day, P=0.015) and serum albumin (23.28 vs. 27.95 g/L, P=0.038). Among patients with positive renal PLA2R-Ag, patients with positive PLA2R-Ab had significantly higher 24-hour proteinuria, when compared to patients with negative PLA2R-Ab (4.57 vs. 3.08 g/day, P=0.005). Among those with positive PLA2R-Ab in sera, their PLA2R-Ab levels were correlated with the estimated glomerular filtration and serum creatinine. Conclusion. Serum PLA2R-Ab exhibits a closer correlation with proteinuric severity and renal function, when compared to renal PLA2R-Ag.

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Secondary Membranous Nephropathy. A Narrative Review

Frontiers in Medicine ◽

10.3389/fmed.2020.611317 ◽

2020 ◽

Vol 7 ◽

Author(s):

Gabriella Moroni ◽

Claudio Ponticelli

Keyword(s):

Nephrotic Syndrome ◽

Lupus Erythematosus ◽

Membranous Nephropathy ◽

Urticarial Vasculitis ◽

Slow Progression ◽

Secondary Membranous Nephropathy ◽

Electron Microscopy Analysis ◽

Microscopy Analysis ◽

Circulating Antibodies ◽

Primary Form

Membranous nephropathy (MN) is a common cause of proteinuria and nephrotic syndrome all over the world. It can be subdivided into primary and secondary forms. Primary form is an autoimmune disease clinically characterized by nephrotic syndrome and slow progression. It accounts for ~70% cases of MN. In the remaining cases MN may be secondary to well-defined causes, including infections, drugs, cancer, or autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), urticarial vasculitis, sarcoidosis, thyroiditis, Sjogren syndrome, systemic sclerosis, or ankylosing spondylitis. The clinical presentation is similar in primary and secondary MN. However, the outcome may be different, being often related to that of the original disease in secondary MN. Also, the treatment may be different, being targeted to the etiologic cause in secondary MN. Thus, the differential diagnosis between primary and secondary MN is critical and should be based not only on history and clinical features of the patient but also on immunofluorescence and electron microscopy analysis of renal biopsy as well as on the research of circulating antibodies. The identification of the pathologic events underlying a secondary MN is of paramount importance, since the eradication of the etiologic factors may be followed by remission or definitive cure of MN. In this review we report the main diseases and drugs responsible of secondary MN, the outcome and the pathogenesis of renal disease in different settings and the possible treatments.

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