Lupus-like membranous nephropathy during the postpartum period expressing glomerular antigens exostosin 1/exostosin 2 and phospholipase A2 receptor: a case report.

Recently, several target antigens of membranous nephropathy (MN), such as phospholipase A2 receptor (PLA2R) and exostosin 1/exostosin 2 (EXT1/2), have been discovered. A 30-year-old woman was referred to our hospital with nephrotic range proteinuria and microscopic hematuria. She was first noted to have proteinuria before pregnancy, and her proteinuria worsened in the postpartum period. A renal biopsy showed MN. Immunofluorescence microscopy showed IgG, IgA, IgM, C3, C4, and C1q depositions in the mesangial area and glomerular capillary walls (GCWs). Regarding the IgG subclass, IgG1 and IgG3 were detected on glomeruli. Electron microscopy showed subepithelial electron-dense deposits (EDDs). EDDs were also detected in paramesangial and subendothelial areas. The diagnosis of membranous lupus nephritis (MLN) was suspected, but she did not fulfill the criteria for systemic lupus erythematosus. Neither anti-nuclear antibody nor hypocomplementemia were detected. We further evaluated glomerular EXT1/2 expressions, which were evident on GCWs. In addition, PLA2R was also detected on GCWs, although serum antibody for PLA2R was negative. She responded to immunosuppressive therapy with decreased proteinuria. In the present case, glomerular PLA2R expression implied the possibility of primary MN. However, pathological findings with a full-house staining pattern and glomerular EXT1/2 expressions were very similar to those of lupus-associated MN. Glomerular PLA2R expression appeared not to reflect immunocomplexes of PLA2R and autoantibody when considering the results for glomerular IgG subclass and the absence of serum anti-PLA2R antibody. Collectively, it is plausible that this was a case of a relatively young postpartum female who developed latent MLN rather than primary MN.

Miyasaka R ，Wada Y ，Takeuchi K ，Abe T ，Uchitsubo R ，Kawamura S ，Sakurabayashi S ，Naito S ，Aoyama T ，Shimizu A ，Takeuchi Y ... -  《-》

A case of PLA2R-positive membranous nephropathy with subsequent development of IgG4-related disease.

Membranous nephropathy (MN) is a common cause of adult-onset nephrotic syndrome. It is also known as a minor but established renal manifestation of Immunoglobulin G4-related disease (IgG4-RD). Previous reports suggest that MN can also be an initial manifestation of IgG4-RD, all of which are phospholipase A2 receptor (PLA2R)-negative MN. We describe a case of PLA2R-positive MN that subsequently developed other manifestations of IgG4-RD. A 60-year-old male with nephrotic syndrome was diagnosed as primary MN with positive staining for PLA2R on the initial renal biopsy, which remained in partial remission with supportive therapy using angiotensin II receptor blocker (ARB) without steroid. About 1 year later, a renal mass was detected during an annual checkup, and contrast-enhanced computed tomography revealed low-density masses in bilateral kidneys and the head of the pancreas. The findings of endoscopic biopsy of the pancreatic mass were consistent with autoimmune pancreatitis (AIP) and the second renal biopsy showed the findings of MN with tubulointerstitial nephritis, both of which led to a diagnosis of IgG4-RD. The second renal biopsy also showed positive PLA2R. The patient received oral glucocorticoid therapy for IgG4-RD, which improved IgG4-related AIP and renal masses and also resulted in complete remission of MN. To our knowledge, this is the first reported case of PLA2R-positive MN with subsequent development of IgG4-RD. It is sometimes difficult to determine whether PLA2R-positive MN occurring with IgG4-RD is primary MN or secondary MN associated with IgG4-RD. The possibility of developing IgG4-RD should be considered even when preceding MN is PLA2R-positive, suggesting of primary MN.

Tanemoto F ，Mimura I ，Abe H ，Nangaku M ... -  《-》

Rare case of exostosin 1/exostosin 2-related membranous lupus nephritis concomitant with dual ANCA- and anti-GBM antibody-associated crescentic glomerulonephritis effectively diagnosed by mass spectrometry: a case report.

Recent developments in mass spectrometry (MS) have revealed target antigens for membranous nephropathy (MN), including phospholipase A2 receptor and exostosin 1/exostosin 2 (EXT1/2). EXT1/2 are known antigens of autoimmune disease-related MN, especially membranous lupus nephritis. We describe the case of an elderly man who developed nephrotic syndrome followed by progressive renal dysfunction. A 78-year-old man presented with rapidly progressive renal dysfunction with proteinuria and hematuria. Three years previously, he had developed leg edema but did not receive any treatment. Laboratory tests showed elevated anti-nuclear antibody (Ab), anti-dsDNA Ab titer, and hypocomplementemia, indicating systemic lupus erythematous. Myeloperoxidase anti-neutrophil cytoplasmic Ab (ANCA) and anti-glomerular basement membrane (GBM) Ab were also detected. The renal pathologic findings were compatible with crescentic glomerulonephritis (GN), whereas non-crescentic glomeruli exhibited MN without remarkable endocapillary or mesangial proliferative change. Immunofluorescence microscopy revealed glomerular IgG, C3, and C1q deposition. All IgG subclasses were positive in glomeruli. Anti-PLA2R Ab in serum was negative. MS analysis was performed to detect the antigens of MN, and EXT1/2 was detected in glomeruli. Therefore, we reached a diagnosis of membranous lupus nephritis concurrent with both ANCA-associated vasculitis and anti-GBM-GN. The simultaneous occurrence of these three diseases is extremely rare. This is the first report of EXT1/2-related membranous lupus nephritis concurrent with ANCA-associated vasculitis and anti-GBM-GN. This case demonstrates the usefulness of MS in diagnosing complicated cases of MN.

Yamazaki T ，Takahashi H ，Takeuchi K ，Sakamoto E ，Tominaga K ，Sakurabayashi S ，Abe T ，Sano T ，Wada Y ，Kuwahara N ，Shimizu A ，Takeuchi Y ... -  《BMC Nephrology》

Concurrent glomerular PCDH7 deposits in PLA2R-associated membranous nephropathy.

Fu N ，Yuan S ，Yang G ，Li H ，Wang T ... -  《-》

Treatment of very high risk membranous nephropathy complicated by pulmonary embolism with glucocorticoids and rituximab: Case report.

We report the efficacy of combination prednisolone and intravenous (IV) rituximab as an immunosuppressive regimen for a young male presenting with extensive venous thromboembolism including a submassive pulmonary embolism secondary to life-threatening nephrotic syndrome from very high risk anti-phospholipase-A2 receptor (PLA2R) positive membranous nephropathy. Initial treatment was with mechanical thrombectomy and anticoagulation. Thereafter, oral prednisolone was initiated to induce remission, during a period of uninterrupted anticoagulation. He subsequently underwent a kidney biopsy for histological confirmation and IV rituximab was administered as definitive treatment. A 33-year-old Chinese male with no chronic conditions presented with shortness of breath and left-sided pleuritic chest pain. He was diagnosed with a submassive pulmonary embolism which was confirmed on computer tomography imaging with additional extensive clot burden in the inferior vena cava and renal veins. Further workup revealed nephrotic syndrome, with proteinuria of 6.5g/day, and serum Albumin 26 g/L, associated with anti-PLA2R of 223 RU/ml. His presenting serum creatinine was 108 µmol/L (CKD-EPI eGFR 77ml/min/1.73m2). Additional workup for malignancy and infections were negative. As part of acute management, immediate anticoagulation was initiated. The patient then underwent endovascular thrombectomy and inferior vena cava filter placement. Given the emergent indication for and need for 4 weeks of uninterrupted anticoagulation, his kidney biopsy had to be delayed. The patient was then preemptively treated with IV Methylprednisolone 500mg for 3 days followed by 0.5mg/kg of oral prednisolone after taking into consideration the specificity of PLA2R positivity for membranous nephrology. After 4 weeks of treatment, serum albumin improved to 32 g/L and anti-PLA2R levels improved significantly to 27 RU/ml. His subsequent kidney biopsy confirmed membranous nephropathy and 2 doses of IV rituximab 1g were administered 14 days apart. Six months after initial presentation, the patient is in partial remission. Albumin has improved to 41 g/L, Anti PLA2R < 2 RU/ml, and proteinuria is 1.18g/day. This case demonstrates that preemptive treatment in patients with anti-PLA2R positive membranous nephropathy can initiated without a histological diagnosis when there are strong contraindications against a kidney biopsy. Treatment with a combination of steroids and IV rituximab could be a viable treatment option for patients with very high-risk membranous nephropathy over conventional therapy with cyclophosphamide.

Khan UF ，Sia C ，Thamboo TP ，Chua HR ，Chan GC ... -  《-》