A Possible Clue for the Production of Anti-Glomerular Basement Membrane Antibody Associated with Ureteral Obstruction and Hydronephrosis

Background: Anti-glomerular basement membrane (anti-GBM) antibody-mediated glomerulonephritis (anti-GBM GN) is an autoimmune disease with rapidly progressive glomerulonephritis. Based on a case report of anti-GBM GN following hydronephrosis, we hypothesized that hydronephrosis may act as a trigger for the development of anti-GBM antibodies. Patients and Methods: We evaluated 11 patients who were diagnosed with hydronephrosis. It was measured with serum anti-GBM antibody. These patients' medical histories as well as risk factors for the development of anti-GBM antibodies and causes of hydronephrosis were reviewed. Renal function and hematuria were also considered. The serum anti-GBM antibody was measured with enzyme-linked immunosorbent assays (ELISA) or chemiluminescent enzyme immunoassays (CLEIA). Histopathological findings of renal biopsy specimens were also evaluated. Results: No patient had a medical history of renal disease. Five patients had a history of smoking. Ten of the 11 patients had renal dysfunction as evidenced by serum creatinine levels of 0.85-13.8 mg/dl, while 8 patients had RBCs in their urinary sediment at the time of diagnosis for hydronephrosis. Two of the patients assessed by ELISA and CLEIA were positive for anti-GBM antibodies. In 1 of these 3 patients, anti-GBM antibodies and renal dysfunction improved upon treatment for hydronephrosis. Another of the 3 patients developed anti-GBM GN, but anti-GBM antibodies and renal dysfunction improved dramatically upon treatment. In the 3rd patient without improved hydronephrosis, anti-GBM antibodies and renal dysfunction remained unchanged. Conclusion: Our results provide insights into the development of anti-GBM antibodies in patients with ureteral obstruction and hydronephrosis.

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SARS-CoV-2 infection and recurrence of anti-glomerular basement disease: a case report

BMC Nephrology ◽

10.1186/s12882-021-02275-4 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Alexander Winkler ◽

Emanuel Zitt ◽

Hannelore Sprenger-Mähr ◽

Afschin Soleiman ◽

Manfred Cejna ◽

...

Keyword(s):

Basement Membrane ◽

Glomerular Basement Membrane ◽

Plasma Cells ◽

Rapidly Progressive Glomerulonephritis ◽

Kidney Injury ◽

Pulmonary Involvement ◽

Pulmonary Haemorrhage ◽

Basement Membranes ◽

High Avidity ◽

History Of

Abstract Background Anti-glomerular basement membrane disease (GBM) disease is a rare autoimmune disease causing rapidly progressive glomerulonephritis and pulmonary haemorrhage. Recently, an association between COVID-19 and anti-glomerular basement membrane (anti-GBM) disease has been proposed. We report on a patient with recurrence of anti-GBM disease after SARS-CoV-2 infection. Case presentation The 31-year-old woman had a past medical history of anti-GBM disease, first diagnosed 11 years ago, and a first relapse 5 years ago. She was admitted with severe dyspnoea, haemoptysis, pulmonary infiltrates and acute on chronic kidney injury. A SARS-CoV-2 PCR was positive with a high cycle threshold. Anti-GBM autoantibodies were undetectable. A kidney biopsy revealed necrotising crescentic glomerulonephritis with linear deposits of IgG, IgM and C3 along the glomerular basement membrane, confirming a recurrence of anti-GBM disease. She was treated with steroids, plasma exchange and two doses of rituximab. Pulmonary disease resolved, but the patient remained dialysis-dependent. We propose that pulmonary involvement of COVID-19 caused exposure of alveolar basement membranes leading to the production of high avidity autoantibodies by long-lived plasma cells, resulting in severe pulmonary renal syndrome. Conclusion Our case supports the assumption of a possible association between COVID-19 and anti-GBM disease.

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Effect of Early Plasmapheresis and Immunosuppressive Therapy on Natural History of Anti-glomerular Basement Membrane Glomerulonephritis

Archives of Internal Medicine ◽

10.1001/archinte.1979.03630400086031 ◽

1979 ◽

Vol 139 (3) ◽

pp. 372 ◽

Cited By ~ 6

Author(s):

Frank J. Bruns

Keyword(s):

Natural History ◽

Basement Membrane ◽

Immunosuppressive Therapy ◽

Glomerular Basement Membrane ◽

History Of

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Etanercept-Induced Anti-Glomerular Basement Membrane Disease

Case Reports in Nephrology and Dialysis ◽

10.1159/000518984 ◽

2021 ◽

pp. 292-300

Author(s):

Saif Al-Chalabi ◽

Henry H.L. Wu ◽

Rajkumar Chinnadurai ◽

Arvind Ponnusamy

Keyword(s):

Basement Membrane ◽

Glomerular Basement Membrane ◽

Rapidly Progressive Glomerulonephritis ◽

Alveolar Haemorrhage ◽

Small Vessel Vasculitis ◽

Drug Induced ◽

Psoriatic Arthropathy ◽

Tnf Α ◽

Life Threatening ◽

Factor Α

Anti-glomerular basement membrane (anti-GBM) disease is a rare form of small-vessel vasculitis that typically causes rapidly progressive glomerulonephritis with or without alveolar haemorrhage. Previously, there has only been one reported case of tumour necrosis factor-α (TNF-α) antagonist-induced anti-GBM disease. Here, we describe the first reported case of etanercept-induced anti-GBM disease. A 55-year-old Caucasian man was referred to our tertiary specialist renal centre with a history of painless macroscopic haematuria. The patient has been receiving weekly etanercept injections over the past 12 months for psoriatic arthropathy. The serum immunology panel results highlighted a significantly raised anti-GBM titre (370.1 U). Etanercept was stopped, and the patient was empirically commenced on pulsed methylprednisolone, cyclophosphamide, and plasma exchange. A renal biopsy showed crescentic glomerulonephritis. Few days after admission, he tested positive for coronavirus disease 2019 (COVID-19), and a decision was made to withhold cyclophosphamide. There was further decline in renal function with hyperkalaemia for which he received 2 sessions of haemodialysis. He was restarted on cyclophosphamide upon discharge. The patient was switched to rituximab treatment afterwards as he developed leucopenia 2 weeks following the commencement of cyclophosphamide. The serum creatinine level continued to improve and remained dialysis-independent. In conclusion, with the increased use of etanercept and other TNF-α antagonists, the prescribing clinician must be aware of the rare but life-threatening drug-induced vasculitis. We recommend careful monitoring of renal indices with the use of this class of medications.

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Anti-glomerular basement membrane disease: an update on subgroups, pathogenesis and therapies

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfy327 ◽

2018 ◽

Vol 34 (11) ◽

pp. 1826-1832 ◽

Cited By ~ 9

Author(s):

Mårten Segelmark ◽

Thomas Hellmark

Keyword(s):

Basement Membrane ◽

Glomerular Basement Membrane ◽

De Novo ◽

Correct Diagnosis ◽

Rapidly Progressive Glomerulonephritis ◽

Human Leukocyte ◽

Pulmonary Haemorrhage ◽

Leukocyte Antigen ◽

Type Iv

Abstract Most patients with anti-glomerular basement membrane (anti-GBM) disease present with rapidly progressive glomerulonephritis with or without pulmonary haemorrhage; however, there are several variants and vigilance is necessary to make a correct diagnosis. Such variants include overlap with anti-neutrophil cytoplasm antibodies-associated vasculitis and membranous nephropathy as well as anti-GBM occurring de novo after renal transplantation. Moreover, patients can present with isolated pulmonary haemorrhage as well as with negative tests for circulating anti-GBM. Virtually all patients with anti-GBM disease have autoantibodies that react with two discrete epitopes on the α3 chain of type IV collagen. Recent evidence suggests that healthy persons have low-affinity natural antibodies reacting with the same epitopes, but most people are protected from developing disease-causing high-affinity autoantibodies by human leukocyte antigen-dependent regulatory T-cells (Tregs). The α3 chain-derived peptides presented by the HLA-DR15 antigen lack the ability to promote the development of such Tregs. The detection of anti-GBM in circulation using the rapid assay test has led to early diagnosis and improved prognosis. However, our present tools to curb the inflammation and to eliminate the assaulting antibodies are insufficient. Only about one-third of all patients survive with functioning native kidneys. More effective therapies need to be developed; agents that inhibit neutrophil recruitment, deplete B cells and cleave immunoglobulin G (IgG) in vivo may become new weapons in the arsenal to combat anti-GBM disease.

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Early onset calciphylaxis following acute kidney injury secondary to anti-glomerular basement membrane antibody disease

BMJ Case Reports ◽

10.1136/bcr-2020-241265 ◽

2021 ◽

Vol 14 (4) ◽

pp. e241265

Author(s):

Sheikh Raza Shahzad ◽

Faris Alfaris ◽

Mustafa Erdem Arslan ◽

Swati Mehta

Keyword(s):

Acute Kidney Injury ◽

Basement Membrane ◽

Glomerular Basement Membrane ◽

Early Onset ◽

Kidney Injury ◽

Caucasian Woman ◽

History Of ◽

Stage Renal Disease ◽

End Stage

Calciphylaxis is commonly associated with end-stage renal disease (ESRD) and renal transplant. We present a rare case of early onset calciphylaxis in a patient presenting with acute kidney injury (AKI) secondary to anti-glomerular basement membrane (anti-GBM) antibody disease. A 65-year-old obese Caucasian woman with type 2 diabetes mellitus and hypertension presented with a 1-month history of painless gross haematuria and worsening lower extremity oedema. Laboratory results indicated AKI and nephrotic-range proteinuria. Anti-glomerular antibodies were elevated. Renal biopsy revealed focal crescentic glomerulonephritis with linear capillary immunoglobulin G staining consistent with anti-GBM antibody disease. She was treated with haemodialysis, plasmapheresis, steroids, bumetanide and cyclophosphamide. Two months later, she developed necrotic lesions on bilateral thighs. Wound biopsy was consistent with calciphylaxis. This case highlights that calciphylaxis, usually seen in patients with chronic kidney disease or ESRD, can manifest in patients with AKI as well.

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Voltage-gated potassium channel Kv1.3 blocker as a potential treatment for rat anti-glomerular basement membrane glomerulonephritis

AJP Renal Physiology ◽

10.1152/ajprenal.00374.2010 ◽

2010 ◽

Vol 299 (6) ◽

pp. F1258-F1269 ◽

Cited By ~ 24

Author(s):

Toshitake Hyodo ◽

Takashi Oda ◽

Yuichi Kikuchi ◽

Keishi Higashi ◽

Taketoshi Kushiyama ◽

...

Keyword(s):

T Cells ◽

Basement Membrane ◽

Potassium Channel ◽

Glomerular Basement Membrane ◽

Memory T Cells ◽

Critical Role ◽

Rapidly Progressive Glomerulonephritis ◽

Effector Memory ◽

Voltage Gated ◽

Effector Memory T Cells

The voltage-gated potassium channel Kv1.3 has been recently identified as a molecular target that allows the selective pharmacological suppression of effector memory T cells (TEM) without affecting the function of naïve T cells (TN) and central memory T cells (TCM). We found that Kv1.3 was expressed on glomeruli and some tubules in rats with anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). A flow cytometry analysis using kidney cells revealed that most of the CD4+ T cells and some of the CD8+ T cells had the TEM phenotype (CD45RC−CD62L−). Double immunofluorescence staining using mononuclear cell suspensions isolated from anti-GBM GN kidney showed that Kv1.3 was expressed on T cells and some macrophages. We therefore investigated whether the Kv1.3 blocker Psora-4 can be used to treat anti-GBM GN. Rats that had been given an injection of rabbit anti-rat GBM antibody were also injected with Psora-4 or the vehicle intraperitoneally. Rats given Psora-4 showed less proteinuria and fewer crescentic glomeruli than rats given the vehicle. These results suggest that TEM and some macrophages expressing Kv1.3 channels play a critical role in the pathogenesis of crescentic GN and that Psora-4 will be useful for the treatment of rapidly progressive glomerulonephritis.

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Membranous nephropathy followed by anti-glomerular basement disease: A case report and review of clinical presentation and treatment

SAGE Open Medical Case Reports ◽

10.1177/2050313x18807621 ◽

2018 ◽

Vol 6 ◽

pp. 2050313X1880762

Author(s):

Claudius Speer ◽

Matthias Martin Gaida ◽

Rüdiger Waldherr ◽

Christian Nusshag ◽

Florian Kälble ◽

...

Keyword(s):

Basement Membrane ◽

Glomerular Basement Membrane ◽

Membranous Nephropathy ◽

Clinical Presentation ◽

Rapidly Progressive Glomerulonephritis ◽

Renal Vein Thrombosis ◽

Simultaneous Occurrence ◽

Rapid Decline ◽

Crescent Formation ◽

Vein Thrombosis

Membranous nephropathy is a common cause of nephrotic syndrome in adults and can be primary or secondary through autoimmune disease, medication, infection, or malignancy. Rapidly progressive glomerulonephritis with crescent formation is rare in patients with membranous nephropathy. Thus, in cases with rapid decline in renal function, after excluding complications such as malignant hypertension, acute hypersensitivity interstitial nephritis, and bilateral renal vein thrombosis, the simultaneous occurrence of a superimposed glomerulonephritis should be considered. We report a 55-year-old man suffering from a biopsy-confirmed primary membranous nephropathy, who developed rapidly progressive glomerulonephritis with anti-glomerular basement membrane antibodies after being affected with membranous nephropathy for 8 years. The kidney biopsy revealed a concurrence of membranous nephropathy and anti-glomerular basement membrane disease. Clinical presentation and treatment of membranous nephropathy followed by anti-glomerular basement membrane disease are discussed based on our observation with promising follow-up.

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