Double-Positive Anti-Glomerular Basement Membrane Antibody and Myeloperoxidase Antineutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis Post COVID-19 mRNA vaccine: A Case Series of 4 Patients.

Rationale: Vaccines remain central to the management of COVID-19 pandemic, including the need for repeat doses of vaccines to boost immunity. There has been an accumulating case count of glomerulopathies temporally associated with COVID-19 vaccination. This case series presents 4 patients who developed double-positive anti-glomerular basement membrane antibody (anti-GBM) and myeloperoxidase (MPO) antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis after COVID-19 mRNA vaccination. This report contributes to our collective knowledge about the pathophysiology and clinical outcomes associated with this rare complication. Presenting Concerns of the Patient: Four patients developed nephritic syndrome within 1 to 6 weeks after receiving a COVID-19 mRNA vaccine (3 post Pfizer-BioNTech and 1 post Moderna vaccination). Three of the 4 patients also had hemoptysis. Diagnosis: Three of the 4 patients had double-positive serology, whereas the fourth patient had renal biopsy findings consistent with double-positive disease, although anti-GBM serology was negative. All patients had renal biopsy findings consistent with double-positive anti-GBM and ANCA-associated glomerulonephritis. Interventions: All 4 patients were treated with pulse steroids, cyclophosphamide, and plasmapheresis. Outcomes: Of the 4 patients, 1 demonstrated complete remission, 2 remained dialysis-dependent, and the fourth is deceased. Of the 2 patients who received repeat vaccination with COVID-19 mRNA vaccine, 1 patient had second serologic flare of anti-GBM in response to the vaccine. Novel Findings: This case series reinforces growing evidence that COVID-19 mRNA vaccine-induced glomerulonephritis is a rare but real phenomenon. Dual ANCA and anti-GBM nephritis can present after the first dose of COVID-19 mRNA vaccine or after several administrations of the vaccine. We are the first to report cases of double-positive MPO ANCA and anti-GBM nephritis after Pfizer-BioNTech vaccination. To our knowledge, we are also the first to report outcomes of repeat COVID-19 vaccination in patients with de novo flare of ANCA and anti-GBM nephritis temporally associated with COVID-19 vaccination.

Lipoprotein Glomerulopathy, First Case Report from Canada.

Lipoprotein glomerulopathy (LPG) is caused by a mutation in the apolipoprotein E gene (APOE) gene and is characterized by lipoprotein thrombi in glomerular capillaries. Here, we describe a case of LPG, the first to be reported from Canada and the first case of LPG in North America to be associated with the APOE Tokyo/Maebashi mutation (p.Leu162_Lys164del, traditional nomenclature 142_144del). A 49-year-old man of Chinese descent with a previous diagnosis of dyslipidemia and a new diagnosis of hypertension was found to have proteinuria on routine urinalysis. Renal biopsy showed markedly dilated glomerular capillaries filled with pale staining mesh-like material that stained positive for Oil-Red-O, consistent with lipoprotein thrombi. APOE gene sequencing confirmed the diagnosis of LPG. The patient was treated with fenofibrate and perindopril. His lipid profile normalized and proteinuria dropped to minimal levels. Repeat renal biopsy 2 years after the first showed resolution of lipoprotein thrombi but with rare residual granular densities by electron microscopy consistent with lipoprotein in the subendothelial space, supporting the hypothesis that this subendothelial material contains precursors to lipoprotein thrombi.

Podocyte Infolding Glomerulopathy, First Case Report From North America.

RATIONALE: Podocyte infolding glomerulopathy (PIG) is a newly described condition with only 37 cases reported worldwide. Due to its rarity, the pathogenesis and evolution of this disease is unclear. This case report contributes to our collective knowledge about the clinical and histological progression of this disease. PRESENTING CONCERNS OF THE PATIENT: Over the course of a year, a 52-year-old Malaysian woman with no known prior medical history developed progressively worsening edema and other findings consistent with nephrotic syndrome. DIAGNOSIS: Unlike most patients with PIG, this patient did not have any autoimmune disease. She was Hepatitis B core antibody positive with a Hepatitis B surface antibody >1000, suggesting prior Hepatitis B infection with immunity. A renal biopsy was performed which was consistent with PIG. A second renal biopsy was done 2 years later which again showed characteristic findings of PIG with worsened podocyte effacement but no interval change in chronicity. INTERVENTIONS: The patient was treated with blood pressure control and renin-angiotensin-aldosterone system (RAAS) blockade with irbesartan and spironolactone. She was also treated with prednisone at 1 mg/kg for 2 months followed by a taper for a total of 7 months of prednisone treatment. OUTCOMES: The patient had a partial response to a course of prednisone. However, since stopping steroids, her proteinuria and renal function has been gradually worsening. TEACHING POINTS: PIG is mostly found in patients of East Asian descent. It presents as proteinuria and is often associated with autoimmune disease but can be idiopathic. It is characterized on renal biopsy by infolding or protrusion of podocyte cytoplasm into glomerular basement membrane, as well as intramembranous cytoplasmic microspherules or microtubules. Atypical membranous nephropathy should be ruled out prior to diagnosis. Unlike membranous nephropathy, PIG usually responds at least partially to steroid monotherapy. To our knowledge, this is the first reported case of PIG from North America. Furthermore, it is the first case of PIG with repeat biopsy showing interval worsening of PIG rather than either resolution of PIG or transformation of PIG to a different diagnosis.

FONDEMENT: La glomérulonéphrite due à l'involution des podocytes (GIP) est une affection nouvellement décrite; seuls 37 cas ont été signalés jusqu'à présent dans le monde. La pathogenèse et l'évolution de cette maladie rare sont donc encore nébuleuses. Ce rapport de cas ajoute au savoir collectif sur sa progression clinique et histologique. PRÉSENTATION DU CAS: Une Malaisienne de 52 ans sans antécédents médicaux connus qui, sur une période d'un an, a développé un œdème s'étant aggravé progressivement et présenté d'autres résultats concordant avec un syndrome néphrotique. DIAGNOSTIC: Contrairement à la plupart des patients ayant reçu un diagnostic de GIP, cette patiente ne présentait aucune maladie auto-immune concomitante. Un résultat positif pour les anticorps anti-HBc et un compte supérieur à 1 000 pour les anticorps de surface contre l'hépatite B suggéraient une infection antérieure par l'hépatite B avec immunité. Une biopsie rénale avait montré un résultat compatible avec une GIP. Une deuxième biopsie rénale effectuée deux ans plus tard a également montré des résultats caractéristiques d'une GIP et une aggravation de l'épanchement des podocytes, mais aucun changement d'intervalle en terme de chronicité. INTERVENTIONS: La patiente a été traitée par maîtrise de la tension artérielle et blocage du SRAA avec irbésartan et spironolactone. Elle a également reçu une dose de 1 mg/kg de prednisone pendant deux mois, qui a par la suite été progressivement réduite. Le traitement à la prednisone s'est étalé sur un total de sept mois. RÉSULTATS: La patiente a répondu partiellement au traitement à la prednisone. Mais depuis l'arrêt des stéroïdes, une aggravation de la protéinurie et une altération de la fonction rénale progressives ont été observées. ENSEIGNEMENTS TIRÉS: La GIP affecte principalement des patients originaires de l'Asie de l'Est. Cette maladie se présente sous la forme d'une protéinurie et elle est souvent associée à une maladie auto-immune, bien qu'elle puisse aussi être idiopathique. À la biopsie rénale, la GIP se caractérise par un repli ou une protrusion du cytoplasme des podocytes dans la membrane basale glomérulaire, de même que par des microsphérules ou des microtubules cytoplasmiques intramembranaires. Une néphropathie membranaire atypique doit être exclue avant de poser le diagnostic. Contrairement à la néphropathie membranaire, la GIP répond généralement, au moins partiellement, aux stéroïdes en monothérapie. À notre connaissance, il s'agit du premier cas signalé de GIP en Amérique du Nord. Il s'agit en outre du premier cas de GIP avec biopsie répétée montrant une aggravation de la maladie pendant l'intervalle plutôt qu'une résolution ou une transformation de la maladie en un diagnostic différent.

A case of aggressive atypical anti-GBM disease complicated by CMV pneumonitis.

BACKGROUND: Anti-glomerular basement membrane (anti-GBM) disease is characterized by circulating IgG glomerular basement membrane antibodies and is clinically expressed as a rapidly progressive crescentic glomerulonephritis (GN), with 30-60% of patients also developing pulmonary hemorrhage. Classically, the renal biopsy shows glomerular crescent formation, bright linear staining of glomerular basement membranes (GBM) for IgG on direct immunofluorescence (IF), and the serologic presence of circulating anti-GBM antibodies. Recently, patients with linear IgG IF staining, undetectable circulating anti-GBM antibodies and glomerular changes atypical for anti-GBM disease have been described as "atypical anti-GBM disease", with a distinctly more benign clinical course than typical anti-GBM disease. We present a case report of a patient with negative anti-GBM serology but positive linear IgG staining by IF, severe diffuse crescentic and endocapillary proliferative glomerulonephritis, and renal failure, complicated by severe pulmonary hemorrhage after immunosuppression, likely due to cytomegalovirus (CMV) pneumonitis. CASE PRESENTATION: A 24-year-old man was admitted to hospital with hemoptysis and renal failure. Investigations for anti-GBM serology by addressable laser bead immunoassay (ALBIA) was negative for anti-GBM antibodies. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis with membranoproliferative features and diffuse circumferential crescents. Direct IF showed strong linear staining for IgG along GBMs. The patient's hemoptysis improved with immunosuppression, but 1 month later he was readmitted with gross hemoptysis, which was refractory to further cyclophosphamide, plasma exchange and rituximab. Bronchoalveolar lavage (BAL) and blood work confirmed CMV pneumonitis, and the patient's hemoptysis resolved with ganciclovir, though he became dialysis dependent. CONCLUSIONS: This case demonstrates an atypical presentation of anti-GBM disease with both crescents and endocapillary hypercellularity and negative serology. The patient is dialysis dependent, unlike most previously described patients with atypical anti-GBM disease. The course was complicated by CMV pneumonitis, which contributed to the severity of the pulmonary manifestations and added diagnostic difficulty.