GROSS HEMATURIA AFTER COVID-19 mRNA VACCINATION: A PROSPECTIVE COHORT STUDY

Introduction: The effective control of coronavirus disease 2019 (COVID-19) can be achieved by implementing a global vaccination strategy. After millions of mRNA vaccines targeting severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been administered worldwide, several reports have shown the cases with gross hematuria (GH) following the mRNA vaccine against SARS-CoV2 in patients with glomerulonephritis, especially immunoglobulin A nephropathy (IgAN). A total of 22 articles including 36 cases of GH after COVID-19 vaccination as on July 31, 2022, were found in PubMed and Google Scholar databases. The most cases which had performed kidney biopsy were IgAN or IgA vasculitis. So, it suggested that GH after COVID-19 vaccination is rerated IgAN. Although there are many reported cases of IgAN after COVID-19 vaccination, the detailed clinical characteristics and outcome have not determined in these patients. Moreover, it remains unclear whether COVID-19 vaccination causes the new onset of nephritis or exacerbates pre-existing nephritis. To address this, herein, we conducted a prospective cohort study over a six-month period. Method(s): We analyzed 82 patients who presented with GH after COVID-19 vaccination and conducted a 6-month observational study. Patients, 18 years or older, who presented to the hospital with GH after COVID-19 vaccination were recruited. All the patients visited either Juntendo University Hospital or Juntendo University Urayasu Hospital between May 11, 2021, and July 31, 2022. Result(s): During the study period, a total of 82 individuals who presented with GH after COVID-19 vaccination were enrolled. The median age of the patients was 38 years;58 cases (70.7%) were females. All the patients received an mRNA COVID-19 vaccine. Most patients showed GH within three days after the second or third dose. Among the 82 patients, 22 had been already diagnosed with IgAN or IgA vasculitis (IgAV) before vaccination, and 45 of the 60 undiagnosed patients had a history of abnormal urinary findings. We performed kidney biopsies on 42 of the 60 undiagnosed patients, who were then diagnosed with IgAN (N=41) or IgAV (N=1). Pathological findings demonstrated that chronic inflammation of glomeruli, such as the expansion of mesangial matrix and glomerular sclerosis, is similarly observed in these newly diagnosed patients compared to patients with IgAN unrelated to vaccination. Finally, we evaluated the levels of biomarkers known to be elevated in IgAN at diagnosis during the course of the study and found that they did not increase. Notably, only few cases showed a slight increase in the level of serum creatinine, and no patients progressed to severe renal dysfunction. Conclusion(s): Present prospective study with 82 cases with GH after COVID-19 vaccination have identified their clinical characteristics and outcome. Furthermore, the acute manifestation of vaccine-induced GH may have highlighted the high prevalence of undiagnosed or preclinical IgAN in Japan. No conflict of interestCopyright © 2023

SLE ONSET POST COVID-19 VACCINATION: COINCIDENTAL or ASSOCIATION?

Background: Numerous immune-mediated diseases fare or new disease onset after SARS-CoV2-vaccination have been reported. There were case reports showed the immune-mediated disease fare post vaccination but study on new disease occurs post Covid-19 vaccination is still lacking. Objectives: To describe two SLE cases that diagnosed post Covid-19 vaccination. Methods: Case report Results: 14 years old girl, post Covid-19 vaccination 1st dose 3 weeks ago presented with 2 day history of giddiness, breathlessness, vomiting and diarrhea prior to admission. She also complained of frothy urine for the past 1 week associated with lower limbs swelling and facial puffiness. Clinical examination noted she had sparse hair, oral ulcers and discoid lupus at the ear concha. She also noted to have periorbital puffiness with pedal edema. Lung auscultation noted bi-basal crepitations. Blood investigation noted ANA positive (1:640, speckled) with low complement 3 (0.1g/L). Her full blood count showed leucopenia (3100 UL) with low lymphocyte count of 810UL. UFEME noted protein of 3 + and red blood cell of 2+ with normal renal profile. Her serum albumin was 22g/L. Chest x ray showed clear lung field with no cardiomegaly. Her 24-hour urine protein showed proteinuria of 2.345g/dl and her renal biopsy showed mesangial proliferative lupus nephritis class iI. She was given intravenous methyl-prednisolone 500mg OD for 3 days and discharged with tapering dose of prednisolone, hydroxychloroquine, calcium supplements, perindopril and frusemide. Another case was a 17 year-old female, post covid-19 vaccination 10 weeks, presented with 3 weeks history of bilateral lower limbs weakness with difficulty in getting up from chair. She also had fever on and off with cough for 1 week. There was no alopecia, oral ulcer, facial rash or photosensitivity. No joints pain. Clinical examination noted presence of proximal myopathy with stable vital signs. Other systemic examinations were unremarkable. Blood investigation noted ANA positive (1: 640, homogenous and speckled) with low complements level (C3 0.19g/L and C4 0.049 g/L).Her creatine kinase was 2367U/L and EMG showed evidence of irritable myopathic process which is consistent with inflammatory myositis. Her TFT was normal. Myositis panel showed anti-Ku and anti-Ro 52 were positive. She was treated as SLE with myositis and intravenous methylprednisolone was given. She discharge well with tapering dose of prednisolone and azathioprine. Her creatine kinase showed improvement with immunosuppression therapy and she was advised on intensive physiotherapy. Conclusion: The onset of these two SLE cases were occurred within the 2 month of post covid-19 vaccination. Whether Covid-19 vaccination direct contribute to the occurrence of SLE remained inconclusive. More studies are required to show its correlation between onset of SLE and Covid-19 vaccination.

Seronegative Full-House Immune Complex Glomerulonephritis Post-mRNA COVID-19 Vaccination

Immunization with COVID-19 mRNA vaccines has been associated with new-onset and relapse of glomerulonephritis (GN)1,2. We present a case of new onset, seronegative, full-house immune-complex GN after mRNA COVID-19 vaccination. A 24-year-old male with history of idiopathic portal vein thrombosis in childhood, portal hypertension post splenorenal shunt and splenectomy 5 years prior presented with 9 weeks of progressive edema, ascites, and foamy urine. His symptoms started then worsened after his 1st and 2nd doses of the mRNA- 1273 COVID-19 vaccination (Moderna). Cr peaked at 3.04mg/dl (baseline 0.7) and UPCR at 50.52 g/g. Serum albumin 0.9 g/dl. Complements were low. ANA and anti-DS DNA were negative as were other serologies. Infectious work up was also negative. Kidney biopsy showed membranoproliferative pattern of injury on light microscopy with one fibrocellular crescent and without IFTA. IF revealed “full house” staining and EM showed severe subepithelial deposits with subendothelial and mesangial deposits. No tubuloreticular inclusions were present (Figure 1). The patient received cyclophosphamide 750 mg and high dose steroids. One month after treatment, Cr improved to 0.92 and proteinuria fell to 6.05g/g. Complements returned to normal. The high potency of mRNA COVID-19 vaccine can induce a robust immune response which may incite or unmask GNs2. Our patient had a rapid and robust response to immunosuppression. Seronegative full-house immune complex GN may occur after receiving mRNA SARS-CoV-2 vaccination and nephrologists should be aware of potential association. Prompt recognition and treatment may lead to favorable outcomes. (Figure Presented)

CLINICAL AND MORPHOLOGICAL FEATURES OF KIDNEY DAMAGE IN PATIENTS WITH ARTERIAL HYPERTENSION DIED OF SARSCOV- 2 INFECTION

Objective: To assess clinical and pathomorphological features of kidney damage in patients with arterial hypertension (AH) who died of the new coronavirus infection COVID-19. Design and method: A complex analysis of 268 kidney autopsies was carried out, including the study of macro- and microscopic changes reflected in the protocols of pathological and anatomical autopsies and identified during the histological examination. In 224 patients (83.6%) with AH, the diagnosis was confirmed by isolating the SARS-CoV-2 RNA using the polymerase chain reaction;in 44 (16.4%) - through computed tomography of the lungs. The causes of deaths were the following: in 31 patients (11.6%) acute myocardial infarction;in 40 (14.9%) cerebrovascular accident;in 11 (4.1%) pulmonary embolism;222 patients (83%) had acute respiratory distress syndrome. The analysis included 130 men aged 36 to 92 (72.6 years old on average) and 138 women aged 40 to 106 (77.1 years old on average). Results: In the kidneys we detected ischemic changes caused by disturbances in the microvasculature. These are stases, sludges, erythrocyte and fibrin thrombi predominantly in the medulla. In the glomeruli diapedesis hemorrhages, mesangial cells proliferation, basement membrane thickening and fibrinoid necrosis of the capillary wall were observed. In the epithelium of the convoluted tubules, a granular, hyaline-drop dystrophy and a necrosis as the extreme degree of the damage were noted. In the kidneys, a pronounced lymphoid and leukocyte infiltration was detected. These changes were accompanied by inflammation and renal failure symptoms. In particular, the level of C-reactive protein was 140.6 ± 7.42 mg/l;blood ferritin 1258.0 ± 110.1 mcg/l;blood leukocytes 15.0 ± 0.67 10

POS-126 PROLIFERATIVE GLOMERULONEPHRITIS WITH MONOCLONAL IgG DEPOSITS;A NOVEL PATHOLOGIC PRESENTATION

Introduction: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a rare form of PGN that mimics immune-complex (IC) GN by light microscopy (LM), but shows monoclonal IgG deposits by immunofluorescence (IF). PGNMID often presents with membranoproliferative (MPGN) pattern or endocapillary hypercellularity. Focal crescents are not uncommon in PGNMID, but diffuse crescentic involvement is very rare. Methods: 78-year-old man with a history of hypertension and multiple cardiovascular comorbidities presented with weakness, dizziness, and anorexia, and was found to have severe hypertension and acute kidney injury with serum creatinine of 12 mg/dl (baseline 1 mg/dl). He was a chronic smoker and alcoholic. He reported productive cough with scanty whitish sputum, but denied hemoptysis. Urine analysis showed marked proteinuria, hematuria, and leukocyturia. Renal ultrasound revealed bilateral decrease corticomedullary differentiation without obstruction. Hemodialysis was initiated. Imaging showed bilateral upper lobe pneumonia with concerns for alveolar hemorrhages. Serology for complements, ANA, dsDNA, ANCA, Hepatitis B and C, Covid19 was negative. Kappa/lambda free light chain ratio was normal. SPEP, UPEP and immunofixation were negative for paraproteinemia. Renal biopsy showed diffuse crescentic and endocapillary PGN with MPGN features, and linear monoclonal IgG3-kappa immune deposits. Given the lack of clinical evidence of cryoglobulinemia and presence of immune-type electron dense deposits without organized substructures by EM, the findings were most consistent with PGNMID. However, the unusual biopsy presentation raised concerns for possible concurrent anti-GBM disease. Subsequently, Solu-Medrol was started followed by prednisone 1 mg/kg. He received 2 sessions of plasmapheresis before anti-GBM serology returned negative. Bone marrow biopsy revealed monoclonal B-cell lymphocytosis with CLL phenotype. Unfortunately, the patient developed Covid19 infection, and passed away before receiving further treatment. [Formula presented] Results: PGNMID is a rare form of renal involvement by monoclonal immunoglobulin deposition that mimics ICGN on renal biopsy. Nephrotic range proteinuria, hematuria and renal insufficiency are usual presentation. Cases of PGNMID classically show IgG3k, in a granular glomerular capillary wall, mesangial, and occasionally subepithelial distribution. By EM, these deposits appear granular typical of ICGN which lack organized substructure. The predominant LM patterns are MPGN and endocapillary hypercellularity. Less frequently focal crescents may be present, but diffuse crescentic involvement is especially rare (~5%). In our case, the diffuse cellular crescents and semilinear to linear GBM staining was unusual. Together with the clinical presentation, the findings prompted concerns for a concomitant Goodpasture syndrome, but anti-GBM antibody returned negative. The pathogenesis is still unclear, but some authors suggest infection as a possible trigger for crescentic transformation in PGNMID. The presence of crescents seem to confer a poorer prognosis and associated with progression to ESRD. Conclusions: Our case is a unique presentation of PGNMID in a patient who presented with clinical and pathologic features concerning for Goodpasture syndrome. PGNMID can rarely present with diffuse crescents and IF findings similar to anti-GBM nephritis in a patient with RPGN. No conflict of interest