The presentation, etiologies, pathophysiology, and treatment of pulmonary renal syndrome: A review of the literature.

Pulmonary renal syndrome (PRS) is a constellation of different disorders that cause both rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage. While antineutrophil cytoplasmic antibody associated vasculitis and anti-glomerular basement membrane disease are the predominant causes of PRS, numerous other mechanisms have been shown to cause this syndrome, including thrombotic microangiopathies, drug exposures, and infections, among others. This syndrome has high morbidity and mortality, and early diagnosis and treatment is imperative to improve outcomes. Treatment generally involves glucocorticoids and immunosuppressive agents, but treatment targeted to the underlying disorder can improve outcomes and mitigate side effects. Familiarity with the wide range of possible causes of PRS can aid the clinician in workup, diagnosis and early initiation of treatment. This review provides a summary of the clinical presentation, etiologies, pathophysiology, and treatment of PRS.

Kidney involvement in children during SARS-CoV-2 Omicron variant pandemic (preprint)

Background As the COVID-19 pandemic persists with the Omicron variants, infection rates in children have rapidly increased compared to previous years. We aimed to investigate the presentation of kidney involvement in children after COVID-19 Omicron variant infection.Methods We retrospectively reviewed the medical records of pediatric patients who presented with kidney involvement between January and August 2022 with a temporal relationship with COVID-19 infection from a Korean single tertiary center.Results Fifteen children presented with kidney involvement after Omicron infection, with a median age of 10.6 (6.8–18.3) years. Aside from fever, cough, sore throat, and diarrhea, none of the patients had severe respiratory symptoms. The median time from infection to renal symptom onset was 3 (0–49) days. Among 10 patients with underlying kidney disease, 6 had previously been diagnosed with nephrotic syndrome (NS) that relapsed after COVID-19 infection, 2 with immunoglobulin A nephropathy (IgAN) showed transient gross hematuria (GHU) with or without acute kidney injury (AKI), and 2 with kidney transplantation presented with AKI. Of the 5 patients without underlying kidney disease, one patient had NS, and the other 4 patients had GHU and proteinuria (PU), of whom one was eventually diagnosed with Henoch-Shönlein purpura nephritis (HSPN). Seven NS patients (1 new-onset, 6 relapsed) showed uneventful remission with corticosteroids. Other than one patient with new-onset HSPN, patients with GHU and PU resolved spontaneously, and patients with AKI also resolved with supportive care.Conclusions Kidney involvement can occur in various, but mostly non-fatal manifestations in children after COVID-19 Omicron variant infection.

Anti-glomerular Basement Membrane Disease Concomitant with MPO-ANCA Positivity Concurrent with High Serum Levels of Interleukin-26 Following Coronavirus Disease 2019 Vaccination.

As coronavirus disease 2019 (COVID-19) vaccine booster campaigns progress worldwide, new reports of complications following COVID-19 vaccination have emerged. We herein report a case of new-onset anti-glomerular basement membrane (GBM) disease concomitant with myeloperoxidase-antineutrophil cytoplasmic antibody positivity concurrent with high levels of interleukin (IL)-26 following the second dose of the Pfizer-BioNTech COVID-19 vaccine. The temporal association with vaccination in this case suggests that an enhanced neutrophilic immune response through IL-26 may have triggered necrotizing glomerulonephritis and a T-cell-mediated immune response to GBMs, leading to the development of anti-GBM antibodies, with an enhanced B-cell response after the vaccination triggering anti-GBM IgG and the onset of anti-GBM disease.

Atypical Anti-Glomerular Basement Membrane Nephritis Occurring After SARS-CoV-2 Infection: A Case Report (preprint)

Background Atypical anti-glomerular basement membrane (GBM) disease, seronegative anti-GBM disease, is a variant where serum anti-GBM antibodies can not be identified in circulation although GBM is stained by Ig-G on an immunofluorescence microscope. We present a 19-year-old male patient who was previously healthy and developed the atypical anti-GBM disease after a SARS-CoV-2 infection. Case presentation The patient, who started to complain of hematuria and hemoptysis on the 3rd day of the negativity of the SARS-CoV-2 infection test, was referred to the hospital on the 15th day. The SerumAnti-GBM antibody of the patient who did not need hemodialysis was negative. Tubulointerstitial nephritis (TIN) was diagnosed in the kidney biopsy of the patient, and corticosteroid therapy was given. However, when the patient's complaints of hematuria and hemoptysis continued, a rebiopsy was performed. A diagnosis of atypical anti-GBM was made after linear IgG staining was detected in the glomerular basement membrane in the pathology of the patient whose serum anti-GBM antibodies were negative. Cyclophosphamide was given to the patient who was under corticosteroid treatment. Conclusion Although the classical anti-GBM disease is known to occur after SARS-CoV-2 infection, according to our knowledge, this case is the first case of atypical anti-GBM disease developed after SARS-CoV-2 infection.

Anti-glomerular basement membrane disease in children: a brief overview.

Anti-glomerular basement membrane disease (Anti-GBM), previously known as Goodpasture syndrome, is an extremely rare cause of rapidly progressive glomerulonephritis and chronic kidney disease stage 5 (CKD5) in children. It is associated with acute pulmonary haemorrhage and it has a poor prognosis. It is classified as an autoimmune, small-vessel vasculitis caused by autoantibody formation against the alpha-3 chain in type IV collagen found in the glomerular basement membrane. Evidence of anti-GBM antibodies in serum or histologically are required for diagnosis. Treatment in children is based on very limited adult data and often involves the use of acute apheresis to rapidly remove circulating factors coupled with intensive immunosuppression such as cyclophosphamide and intravenous corticosteroids. There is also an emerging role for the use of biologic agents such as B cell depletion. The evidence base in children with anti-GBM disease is extremely limited. Multi-centre international collaboration is required to provide insight into this disease, better describe its prognosis and work towards improving outcomes. This review article summarises the key features of this disease in children, highlights treatment options and considers areas of unmet need.

A case of anti-GBM nephritis following centipede bites and COVID-19 vaccination.

A case of newly developed anti-glomerular basement membrane (GBM) glomerulonephritis (GN) following centipede bites and COVID-19 vaccination is presented. A 70-year-old woman presented for investigation of mild fever, generalized fatigue, and macroscopic hematuria with no past history of renal disease. One year earlier, she had been bitten by a centipede. Based on the governmental policy, she was given the first COVID-19 vaccination, and the second injection was planned 3 weeks later. Accidentally, she was again bitten by a centipede, and the injured site had swollen severely. Based on a physician's judgment, the interval between vaccinations was extended to 8 weeks. One week after the second vaccination, macroscopic hematuria occurred suddenly, coincident with mild fever. Her serum anti-GBM titer was above the upper limit. There was no pulmonary involvement. Renal pathology showed anti-GBM GN, and she was treated with corticosteroid pulse therapy followed by sequential plasmapheresis. She had advanced renal dysfunction, but was independent of dialysis therapy during the one month of the remission induction therapy phase, and she is being treated with immunosuppressant therapy. Both vaccination and animal bites skew towards Th1 immunity, a key mechanism involved in the development of necrotizing GN evoked by anti-GBM antibody. Though there is no direct evidence for causality linking centipede bites, vaccination, and anti-GBM GN, the risk of anti-GBM GN appears to be increased by excessively induced Th1 immunity.

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

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.