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Recent advances in the management and understanding of IgG4-related kidney disease (RKD) have emphasized the importance of urgent treatment in IgG4-related tubulointerstitial nephritis. On the other hand, to avoid long term glucocorticoid toxicity, strategies for early withdrawal of steroid or combination of immunosuppressants, such as rituximab, a...
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Context 1
... or urine marker (s) or decreased kidney function with elevated serum IgG level, hypocomplementaemia, or elevated serum IgE level 2. Abnormal renal radiologic (1) Bilateral lacrimal gland swelling (2) Bilateral submandibular or parotid gland swelling (3) Imaging findings compatible with type 1 autoimmune pancreatitis (4) Imaging features of retroperitoneal fibrosis Definite: 1 + 3 + 4a +4b 2 + 3 + 4a + 4b 2 + 3 + 5a 1 + 3 + 4a + 5a or 5b 2 + 3 + 4a + 5b ...Context 2
... the 2019 ACR/EULAR classification criteria for IgG4-RD define positivity for anti-proteinase (PR) 3 or anti-myeloperoxidase (MPO) ANCA by ELISA as excluding a diagnosis of IgG4-RD [16,17]. The key points to differentiate between IgG4-RKD and AAV are summarized in Table 2. ANCA-positivity in patients with high serum IgG4 concentrations does not always indicate a diagnosis of AAV rather than of IgG4-RD [24,25]. ...Citations
... Among the glomerulonephritis observed in IgG4-RDs, MN is the most common, accounting for approximately 7% of IgG4-TIN cases in a previous report [7]. However, the precise frequency of IgG4-related MN remains unclear because it has been also reported that 38% of IgG4related MN cases do not involve TIN [8]. The onset timing of IgG4-related MN varies; while most IgG4related MN cases develop simultaneously with or several years after the involvement of other organs, rare cases precede manifestations in other organs [8]. ...
... However, the precise frequency of IgG4-related MN remains unclear because it has been also reported that 38% of IgG4related MN cases do not involve TIN [8]. The onset timing of IgG4-related MN varies; while most IgG4related MN cases develop simultaneously with or several years after the involvement of other organs, rare cases precede manifestations in other organs [8]. In cases of IgG4-related MN without the involvement of other organs, it is difficult to distinguish between primary MN and IgG4-related MN at the onset. ...
... The standard treatment for IgG4-related MN remains to be established, but it often requires immunosuppressants in addition to glucocorticoids because of its poor steroid responsiveness compared to IgG4-TIN [8]. Similar to our case, a previous study reported that a combination of glucocorticoids and cyclosporine was effective for IgG4-related MN. ...
Although immunoglobulin G4 (IgG4)-related kidney diseases are typically characterized by tubulointerstitial nephritis with abundant infiltration of IgG4-positive plasma cells and fibrosis, there have been relatively rare cases of IgG4-related glomerulonephritis. Several cases of IgG4-related disease (IgG4-RD) following coronavirus disease 2019 (COVID-19) mRNA vaccination have been reported. However, there are no reports of IgG4-related glomerulonephritis following COVID-19 vaccination. Herein, we present a case of IgG4-related membranous nephropathy (MN) occurring after COVID-19 vaccination.
A 69-year-old Japanese male presented to our hospital with edema that started the day after his second COVID-19 vaccination. The patient exhibited nephrotic syndrome and was diagnosed with MN based on the results of a kidney biopsy. Although serum IgG4 levels were elevated to 946 mg/dL, no evidence of organ involvement suggestive of IgG4-RD was observed. Treatment with prednisolone and cyclosporine resulted in complete remission, and immunosuppressive agents were tapered. However, one month after discontinuing the immunosuppressive agents, the patient was readmitted with swelling around the submandibular glands and exertional dyspnea. Serum IgG4 level was markedly elevated at 2,320 mg/dL, and computed tomography revealed submandibular gland swelling and thickening of the interlobular septum and bronchovascular bundles in both lungs. The patient was diagnosed with IgG4-RD based on elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in the submandibular gland biopsy. Upon resuming treatment with prednisolone, the symptoms attributed to IgG4-RD improved within a few days. In cases of nephrotic syndrome following COVID-19 vaccination, it may be advisable to conduct detailed examinations to assess the possibility of the development of IgG4-RDs.
... As previously mentioned, TIN is the most common renal pathologic finding in IgG4-RD, but membranous nephropathy is the most common glomerular lesion, and its relationship to the PLA2R antibody is unknown. As far as we are aware, 13 cases of IgG4-RD with membranous nephropathy without TIN have been reported [11]. It is possible that renal dysfunction at diagnosis is less severe in MN without TIN than in MN with TIN. ...
... It is possible that renal dysfunction at diagnosis is less severe in MN without TIN than in MN with TIN. In cases of MN complicated with TIN, 9/21 (42%) had Cr > 2.0 mg/ dL at diagnosis, while 1/13 (7%) had Cr > 2.0 mg/dL in cases of MN without TIN [11]. In addition, three cases of PLA2R antibody-positive MN associated with IgG4-RD have been reported, and serum PLA2R antibody was identified in only one case. ...
Background
IgG4-related disease (IgG4-RD) is a fibroinflammatory disease that affects multiple organs, including the pancreas, lacrimal glands, salivary glands, periaortic/retroperitoneum, and kidney. Interstitial nephritis is a typical renal disorder associated with IgG4-RD, but membranous nephropathy is also seen in some cases.
Case presentation
Herein we report on the case of a 77-year-old male patient with nephrotic syndrome and IgG4-related lung disease. His serum phospholipase A2 receptor (PLA2R) antibody was positive. His renal biopsy specimen was also positive for PLA2R.
The renal biopsy specimen showed membranous nephropathy with equal IgG3 and IgG4 immunofluorescence staining and no interstitial nephritis, suggesting IgG4-RD manifesting as membranous nephropathy.
Conclusions
Nephrotic syndrome caused by membranous nephropathy is sometimes associated with IgG4-RD. In such cases, even if serum PLA2R antibody is positive, it should be considered that the membranous nephropathy may be secondary to IgG4-RD.
... Diagnostic criteria of IgG4-RD may in fact be fulfilled by various diseases with hypergammaglobulinemia, including antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), autoimmune diseases such as systemic lupus erythematosus (SLE), and multicentric Castleman's disease. This could be a potential cause of diagnostic pitfalls [4,7]. ...
Purpose
Tubulointerstitial nephritis (TIN) has various etiologies, including IgG4-related disease (IgG4-RD), autoimmune diseases, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and others. IgG4-positive plasma cell infiltration can occasionally be found in TIN unrelated to IgG4-RD. Therefore, there may be problems with usage of IgG4 immunostaining to differentiate between TIN with and TIN without IgG4-RD. This study aimed to compare the proportion of plasma cells that are positive for each IgG subclass and to clarify the predominant IgG subclass trends and clinical characteristics associated with IgG4-RD and non-IgG4-related interstitial nephritis.
Methods
The study enrolled 44 cases of TIN: 6 of IgG4-RD, 8 of autoimmune disease, 9 of AAV, and 21 of unknown disease group. In addition to clinical characteristics, IgG subclass composition of interstitial plasma cells was evaluated among 4 groups by immunohistochemistry.
Results
IgG1 was the predominant IgG subclass in TIN unrelated to IgG4-RD. In the IgG4-RD group, the IgG subclass rate was high in both IgG1 and IgG4. The rate of average IgG4-positive cells was significantly lower in the autoimmune disease group and unknown disease group compared with the IgG4-RD group.
Conclusion
The present study revealed IgG1-dominant immune profiles of TIN unrelated to IgG4-RD. Further investigation is required to elucidate the clinicopathological differences between IgG1-dominant and IgG4-dominant groups in IgG4-RD.
... In addition to unexplained renal dysfunction, patients may have elevated serum IgG4 levels and hypocomplementemia. When hypocomplementemia and/or elevated serum IgG4 and/or total IgE levels are present, IgG4-RKD is more likely to be detected [30], especially if Ig4-RD has already been diagnosed. The EULAR classification includes hypocomplementemia (C3, C4, or both) among the diagnostic markers of IgG4-RKD [10]. ...
... When these lesions are detected without extrarenal localization of IgG4-RD, they could be mistaken for neoplastic masses, resulting in nephrectomy. Detecting IgG4-RKD in this setting is difficult: extrarenal IgG4-RD is highly suggestive of IgG4-RKD if renal lesions respond to corticosteroids [21,30]. ...
... Indirect kidney involvement can also be observed in the retroperitoneal involvement when retroperitoneal fibrotic tissue encloses the ureters ab extrinseco, causing obstructive AKI and/or CKD (see [30] for further details). ...
Fibroinflammatory diseases are a group of rare pathologies in which the hallmark is the exuberant deposition of fibrotic tissue and inflammatory cellular infiltrates, characteristic of the specific disease. A sclerotic mass develops within soft tissues and/or organs, damaging and replacing them, with effects ranging from asymptomatic to life-threatening clinical manifestations. The kidneys and urinary tract can be involved in some of these diseases, which can lead to acute kidney injury, chronic kidney disease, and even end-stage kidney disease. IgG4-related disease, retroperitoneal fibrosis, and Erdheim–Chester disease are the three fibroinflammatory disorders that can involve the kidneys. Only a timely and accurate collection of clinical, radiological, metabolic, laboratory, and histological data allows prompt diagnosis and targeted treatment of these pathologies, allowing the stoppage of the evolution of renal and systemic manifestations, which can lead to complete remission. The epidemiology, clinical and histological features, and management of these conditions are herein described in a narrative fashion.
... 5 The most common presentations of IgG4-related kidney disease include IgG4 tubulointerstitial nephritis, membranous nephropathy, hypocomplementemia and obstructive nephropathy induced by retroperitoneal fibrosis. 6,7 Rarely, IgG4-RD can manifest as a unilateral renal pelvic or ureteropelvic mass. Patients with IgG4-RD may undergo nephrectomy if the lesion is misdiagnosed as urothelial malignancy. ...
Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune-mediated disorder with heterogeneous multiorgan manifestations. Early identification and treatment of IgG4-RD are crucial for organ function recovery. Rarely, IgG4-RD manifests as a unilateral renal pelvic soft tissue mass that may be misdiagnosed as urothelial malignancy, resulting in invasive surgical intervention and organ damage. Here we present a 73-year-old man who had a right ureteropelvic mass with hydronephrosis detected by enhanced computed tomography. Right upper tract urothelial carcinoma and lymph node metastasis was highly suggested based on the image findings. However, IgG4-RD was suspected due to his past history of bilateral submandibular lymphadenopathy, nasolacrimal duct obstruction, as well as a high serum IgG4 level of 861 mg/dL. The ureteroscopy with tissue biopsy showed no evidence of urothelial malignancy. His lesions and symptoms improved after glucocorticoid treatment. Hence, a diagnosis of IgG4-RD was made, with the phenotype of classic Mikulicz syndrome with systemic involvement. The manifestation of IgG4-RD as a unilateral renal pelvic mass is rare and should be kept in mind. A ureteroscopic biopsy and serum IgG4 level measurement can help in the diagnosis of IgG4-RD in patients with a unilateral renal pelvic lesion.
A 68-year-old man with type 2 diabetes mellitus was admitted with decreased renal function. He had high IgG4 (1070 mg/dL) and hypocomplementemia (CH50, 25 U/mL). Kidney biopsy showed tubulointerstitial nephritis with IgG4-positive plasma cell infiltration. Four years later, a second kidney biopsy revealed a new manifestation of membranous nephropathy and tubulointerstitial nephritis with exacerbated fibrosis formation. Six years later, the patient developed bullous pemphigoid, which was thought to be caused by DPP4 inhibitors, so DPP4 inhibitor treatment was discontinued. The use of DPP4 inhibitors correlated with changes in renal function, and the patient was diagnosed with IgG4-related kidney disease related to DPP4 inhibitors.
Tertiary lymphoid tissue (TLT) develops at sites of chronic immune stimulation, including infection, autoimmune disease, transplant rejection, and cancer. Recently, TLT has been focused on an indicator for poor renal prognosis in various kidney diseases. In cryoglobulinemic vasculitis (CV), specific glomerular and vascular lesions are seen; however, tubulointerstitial lesions are usually nonspecific. We herein report the case of a 74-year-old man with idiopathic CV with rare tubulointerstitial lesions, such as tubulointerstitial nephritis (TIN) with IgG4-positive plasma cell infiltration and TLT. To our knowledge, this is the first report identifying TLT in the kidney biopsy in a patient with CV. Glucocorticoid improved the renal outcome. The association between CV and TIN with TLT remains unknown.
Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by chronic activation of the immune system with subsequent tissue fibrosis. It can affect a wide variety of different organ systems. The most common form of renal involvement (IgG4-RKD) is tubulointerstitial nephritis (TIN) with characteristic infiltrates of IgG4-positive plasma cells in the interstices and storiform fibrosis. Rarer forms with glomerular involvement and urinary obstruction caused by retroperitoneal fibrosis can also occur. The clinical presentation of IgG4-RKD is usually unspecific with only impaired kidney function and an unremarkable urinalysis. An elevated serum IgG4 level can strengthen the suspected diagnosis of IgG4-RKD. Cross-sectional imaging often demonstrates characteristic lesions close to the renal cortex, which are difficult to differentiate from malignancies. Although a rapid clinical response of IgG4-RKD to treatment with glucocorticoids is characteristic, there is often only a partial improvement in kidney function. Recurrences are frequent and the optimal management of follow-up and long-term treatment is still unclear. This article explains the various forms of IgG4-RKD in more detail.
