Sarcoidosis-Associated Immune Thrombocytopenic Purpura and Focal Segmental Glomerulosclerosis

Purpose of study A 32-years old male with known multi-system sarcoidosis in remission for 5 years off treatment presented to the emergency room with complaints of generalized weakness, hematemesis, epistaxis, and bruises. Physical examination was notable for petechiae, ecchymosis along with papules and plaques suggestive of active sarcoid skin lesions on his extremities. Laboratory workup was significant for thrombocytopenia 3000/uL, acute kidney injury with sub-nephrotic proteinuria. Peripheral blood smear did not show evidence of hemolysis and direct Coombs test was negative. Infectious workup including COVID-19, HIV, and hepatitis serologies were negative. Computed Tomography (CT) of chest, abdomen, and pelvis showed mild splenomegaly and an increased number of sub-centimeter hilar and mediastinal lymph nodes. The patient was treated with dexamethasone 40 mg daily for 4 days and intravenousimmunoglobulins (IVIG-2 gm/kg) for possible Immune Thrombocytopenic Purpura (ITP) with improvement in platelet count to 42000/uL by day 3. His workup for AKI and sub-nephrotic proteinuria was negative apart from a positive ANA (1: 160) with low complements. The anti-phospholipid antibody panel was negative. The ACE level was markedly elevated (>80U/L). The patient could not get a renal biopsy due to severe thrombocytopenia. He was discharged but was re-admitted in 15 days for severe thrombocytopenia of 1000/uL, epistaxis, and bruising. We continued high dose steroids along with IVIG 1 gm/kg for refractory ITP with minimal response and started anti-CD20 agent (Rituximab) 375 mg/m2 weekly with thrombopoietin-receptor agonist (Eltrombopag). His platelets count improved in response to treatment and subsequent renal biopsy showed focal and segmental glomerulosclerosis along with mild interstitial fibrosis, tubular atrophy thought to be from long standing sarcoidosis. There was also evidence of focal arteriosclerosis with no evidence of granulomas, immune complex, complement, or IgG4 deposition. Given skin lesions, thrombocytopenia, extensive lymphadenopathy, and renal involvement with markedly elevated ACE levels the overall picture was consistent with active multi-system sarcoidosis. His platelet count increased to 177,000/uL at the time of discharge. Currently, the patient is on slow steroid taper along with Eltrombopag 25 mg every other day without any recurrence of his symptoms so far. Methods used We described one case of sarcoidosis with hematologic and renal involvement. Summary of results Our patient developed hematologic and renal complications approximately 6 years after being diagnosed with sarcoidosis. Initially, he did not demonstrate sufficient clinical response to IVIG and high dose steroids. However, after a course of anti-CD20 agent (Rituximab) and with the addition of thrombopoietin-receptor agonist (Eltrombopag) he showed improvement of platelet count and stabilization of the renal function. Currently, the patient is receiving maintenance therapy with Prednisone 7.5 mg daily along with Eltrombopag 25 mg twice weekly with no recurrence of ITP and stable renal function. A further decision on whether the patient needs another cycle of Rituximab will be determined by the patient's clinical course. Conclusions Highly variable manifestations of Sarcoidosis can pose a significant diagnostic and therapeutic challenge as can be seen from our case. ITP is a rare hematological manifestation of sarcoidosis and addition of anti-CD20 agents should be considered in refractory cases.

Kidney Biopsies during the Covid-19 Outbreak: A Series of Cases

Introduction: Kidney disease due to COVID-19 has been described with several presentations, both in acute phase and in posterior timing of the infection, and kidney biopsy is important for an ideal management. But the process of adequately perform a biopsy during the pandemic entails risks, as being the exposed and infected by the SARS-CoV-2. Besides of the usual potential complications, such as post-biopsy hemorrhage, that may require admission in an already crowded medical structure. For these reasons, attainment of kidney biopsies was limited to those who without an adequate histopathological diagnosis, were at higher risk of inappropriate management, as well as a pathology secondary to the SARS-CoV-2 could be ignored. The aim of this study is to perform a description of the cases biopsied during the SARS-CoV-2 pandemic, being emphasized those whose indication emerged because of the viral infection. Method(s): Descriptive study of the clinical presentation in addition to histopathological findings of cases requiring kidney biopsy during the period of March 2020 - July 2021. Result(s): A total of 37 cases were collected, with a median age of 40 years (range: 60), 51% males and 73% with known history of hypertension. A 35% of the cases presented nephrotic syndrome;with average proteinuria of 4189.5mg/24h. The most frequent histopathological diagnosis was focal segmental glomerulosclerosis (FSGS), accounting for 40% of the cases. 4 patients required biopsy after COVID-19. One of them presented with Acute Kidney Injury (AKI) during the acute phase of the SARS-COV-2 infection with prolonged hemodialysis requirement;presenting histopathological diagnosis of global and segmental glomerulosclerosis. Another case of AKI during the acute phase of infection and subsequent proteinuria presented global and segmental glomerulosclerosis with collapsing characteristics;while 2 cases due to nephrotic syndrome post-infection, presented histological data of minimal change disease and FSGS with acute tubular injury. Conclusion(s): Regardless of the appearance of a new pathology that affects the kidneys, the incidence of entities such as FSGS persists with greater frequency. However, that does not diminish the importance of performing renal biopsies, since this is an essential tool for management in cases where there is overlap of specific glomerual diseases with COVID-19. No conflict of interestCopyright © 2023

Covid-19 Vaccination Induced Minimal Changed Disease

Introduction: Minimal change disease (MCD) accounts for approximately 15% of adults with idiopathic nephrotic syndrome (NS). We report the case of minimal change disease in a patient who presented with signs and symptoms of NS following Covid-19 immunisation vaccine. Method(s): Case: A 58-year-old male with negligible past medical history developed generalised swelling 2 days following receiving the Pfizer Covid-19 booster. On examination, he had a blood pressure of 130/80 and anasarca. Relevant laboratory results include a creatinine of 123, estimated glomerular filtration rate (eGFR) of 55, albumin of 9, urine protein: creatinine ratio of 713, and hyaline casts of moderate quantity. A kidney biopsy revealed glomerular sclerosis appropriate for age, and normal vessels and tubules. Immunofluorescence showed negative serology. A diagnosis of minimal change disease was made. The patient was treated with high dose prednisone at 1mg/kg/day and went into remission. The patient was followed up 2 months after admission, and investigations revealed a creatinine of 70, eGFR of >90, albumin of 34 and urine protein:creatine ratio of 58. Result(s): / Conclusion(s): Discussion and conclusion: This is the first case of Covid-19 vaccination induced NS reported in New Zealand. Theorised mechanism of injury includes T-cell mediated immune dysregulation, leading to glomerular disease (Sahin et al., 2020). Different glomerular diseases have been reported to occur for the first time following the Covid-19 vaccination (Klomjit et al., 2021). There has also been reports of reactivation of disease following Covid-19 immunisation (Hartley et al., 2022 and Leong et al., 2021). mRNA vaccination induced NS should be considered in all patients presenting with apparent idiopathic NS. This is especially important as we continue to learn more about the Covid-19 vaccination. No conflict of interestCopyright © 2023

An unusual presentation of malignant Invasive Mucinous Adenocarcinoma of Lung mimicking Pulmonary Renal syndrome

Background: A 54-year- old male presented to our centre with a chronic non-productive cough and breathlessness. Recent history of COVID treated and resolved few months back. He had a history of brain surgery performed five years back but details not known. Physical examination revealed no oedema and bilateral coarse creps with bronchiolar breathing. Laboratory findings indicated neutrophilic leucocytosis, elevated inflammatory markers, with elevated troponin I and D dimers. Urine analysis suggested microscopic haematuria with sediments. While 24 hour quantification revealed sub nephrotic proteinuria. As auto immune workup and vasculitis profile was negative and patient has not improved in spite of standard of therapy hence we went ahead with CT-Chest indicating ground-glass opacities in bilateral lung parenchyma and prominent interlobular/intralobular septal thickening. Then Bronchoscopy done which revealed the blood-stained secretions in the main stem bronchi and diffuse alveolar haemorrhage in bilateral bronchial segments indicating an inflammatory study, while tuberculosis diagnostic panel and infective bio fire panel in BAL was negative. Meanwhile, his repeat BAL culture suggested Carbapenem resistant Acinetobacter baumannii complex infection. As the patient did not respond to the standard of care for vasculitis. Probability considered was a small vessel vasculitis (namely Granulomatous polyangiitis) was considered due to lung manifestation involving upper respiratory tract with epistaxis, neutrophilic leucocytosis, elevated acute reactive protein, and renal manifestation including microscopic haematuria and proteinuria. However he responded poorly to conventional standard of treatment including pulse steroids and IVIG. Hence after MDT discussion we proceeded with lung biopsy which showed linear cores of lung tissue infiltrated by a malignant neoplasm and acinar pattern suggesting Invasive mucinous adenocarcinoma. Hence we went ahead with the biopsy diagnosis for the treatment plan. As he was to be started on chemotherapy, but he suddenly collapsed and went into hypotension, bradycardia, and cardiac arrest. In spite of high supports and post 4 cycles of CPR, was unable to revive and sadly succumbed to his illness. Discussion(s): In this rare case, the original diagnosis pointed to the pulmonary-renal syndrome, an autoimmune disease characterized by diffuse pulmonary haemorrhage and glomerulonephritis. However, negative autoimmune antibodies and vasculitis profile along with lung biopsy results indicated an unusual case of malignant lung adenocarcinoma presented with pulmonary renal syndrome. Conclusion(s): In cases suggesting pulmonary-renal syndromes, if autoimmune work up is negative and response is suboptimal relook the diagnosis.

Effect of the COVID-19 Pandemic on Clinical Phenotype of Glomerular Disease: Single Centre Experience

Background: Presenting features for glomerular disease can be varied, including but not exclusively, acute kidney injury, nephrotic syndrome or haemo-proteinuria. At our regional tertiary centre we conducted a retrospective study to see whether clinical presentations of glomerular diseases had changed during the COVID-19 pandemic. Method(s): In this study, new and repeat native renal biopsies were included from January 2018 to October 2021. Glomerular pathologies of interest included minimal change disease, membranous nephropathy, IgA nephropathy, lupus nephritis and pauciimmune glomerulonephritis. We looked at three periods of time: prior to the start COVID-19 pandemic in 2018/19;during the COVID-19 pandemic in 2020;and after the introduction of COVID-19 vaccines in 2021. Result(s): 263 biopsies were identified over the 4-year period. IgA nephropathy - n = 13. Lupus nephritis - n = 43. The different classes of lupus nephritis are shown in (see figure 1) Minimal change disease - n = 57. All presented with the nephrotic syndrome. Between 6-25% over the study period presented with AKI (mean 19%) Pauci-immune glomerulonephritis - n = 85. Between 81%-91% over the study period presented with AKI, or AKI on CKD (mean 84%) Membranous glomerulopathy - n = 66. 50%, presented with the nephrotic syndrome. 20% presented with AKI in addition to proteinuria. Conclusion(s): Our analysis has not shown a significant change in clinical presentations of glomerular disease. There has not been an increased propensity in presenting with AKI in minimal change disease or membranous nephropathy. We saw the highest proportion of class IV lupus nephritis in 2021.

Effect of the COVID-19 Pandemic on Incidence of Glomerular Disease: A Single Centre Report

Background: Glomerular disease carries a significant burden of morbidity and mortality. There is emerging evidence of the impact of the COVID-19 pandemic and COVID-19 vaccination on glomerular disease. The aim of the study was to retrospectively analyse our experience of the incidence of glomerular disease between 2018 and 2021. Method(s): Native renal biopsy results were reviewed to compare the incidence of glomerular disease prior to the COVID-19 pandemic (2018/19);prior to development of COVID-19 vaccination (2020);and after the introduction of COVID-19 vaccines (2021). Biopsy data from January 2018 to October 2021 were collated from pathology records for all glomerular disease patients in our unit. We focused on the incidence of IgA nephropathy, lupus nephritis, minimal change disease, membranous nephropathy and pauci-immune glomerulonephritis. Result(s): 263 native biopsies were performed;45 biopsies in 2018, 75 in 2019, 65 in 2020 and 78 in the first ten months of 2021. The proportional incidence of each disease is shown in figure 1. The incidence of membranous nephropathy was noted to be higher in 2021, coinciding with the introduction of the COVID-19 vaccine programme in the UK, from an average of 23% of cases between 2018-2020, to 31% in the first ten months of 2021. The overall incidence of glomerular disease, excluding vasculitis, seemed to have fallen during 2020. Conclusion(s): The emergence of COVID-19 does not appear to have caused a significant increase in the overall incidence of glomerular disease in our population. We noted an increase in the incidence of membranous nephropathy following the introduction of the COVID-19 vaccination programme in 2021. The relatively lower incidence in 2020 could be related to limited access to primary health care practitioners and consequent reduction in referrals to secondary care at the time.

COVID VACCINE ASSOCIATED GLOMERULAR DISEASES- A CASE SERIES

Introduction: Vaccination is a known trigger for the development of de-novo or flare of glomerular diseases. Here we present a case series of fourteen patients with COVID vaccine- associated glomerular diseases (CVAGD). Methods: Patients with new onset proteinuria, hematuria or renal failure after SARS- CoV2 vaccine were included in the study. Demographic and clinical details were collected and laboratory investigations including serum creatinine, albumin, urine microscopy and urine spot protein creatinine ratio were done. Renal biopsy specimens were subjected to light microscopy and immunofluorescence examination. Results: We cared for 14 patients with CVAGD. Of them, eight patients were males. The mean age was 25.7 years. Three patients had relapse of their previous disease while eleven patients had no previously detected renal diseases. Eleven patients had received COVISHIELD and three had received COVAXIN. All patients presented after the first vaccine dose. At presentation, seven patients had nephrotic syndrome, two patients had rapidly progressive renal failure and five patients had nephritic syndrome. The mean duration of symptom onset after vaccination was 18 days. Renal biopsy revealed IgA nephropathy in 3 patients, endocapillary proliferative glomerulonephritis in 2 patients, minimal change disease in 5 patients, pauci- immune glomerulonephritis (ANCA associated vasculitis) in one patient, lupus nephritis ISN/RPS class 3 in one and focal segmental glomerulosclerosis in two patients. There was no history of COVID infection in any of our patients. Three patients had renal failure at presentation but none required renal replacement therapy. The patients with MCD and FSGS were treated with steroids, patients with ANCA vasculitis and lupus nephritis were managed with the appropriate Cyclophosphamide and steroid regimens while the others were managed conservatively with anti-proteinuric medications. On follow up, five patients (One IgAN, three MCD, one endocapillary proliferative GN) achieved complete remission of proteinuria and resolution of renal failure, while the remaining eight patients achieved partial remission. One patient with MCD had a relapse of proteinuria 3 weeks after achieving partial remission, he responded well to steroid therapy. All 14 patients remain on close follow up. Conclusions: Although causality cannot be definitively established, there is a definite temporal association between the presentation of glomerular diseases and COVID vaccination, in the absence of other inciting factors. Hence, new-onset or relapse of glomerular diseases presenting post vaccination, although rare, should be observed as a possible adverse event. Intriguing questions such as how to proceed with the vaccination schedule in patients with CVAGD and would changing the vaccine type reduce the risk of relapse remain unanswered. No conflict of interest

Management of a Pregnant Patient with ARDS Due to COVID-19: A Case Report

Introduction: In the obstetric population, ARDS due to COVID- 19 has been found to have worse outcome. Treatment of severe COVID-19 has been a real challenge world over. This case report is aimed at giving an insight to the management of COVID-19 in a pregnant patient. Case report: A 36-year-old primi with 33 weeks and 2 days of gestation was admitted with fever, cough, and shortness of breath for 4 days. The patient was found to be positive for COVID. The patient was initially admitted in the wards. In view of worsening oxygenation patient was shifted to the ICU. The patient was initiated on high flow nasal cannula with FiO2 100%, but maintained saturation of 82-84% with that. Hence, patient was intubated and initiated on mechanical ventilation. Post intubation patient maintained a saturation of 86-88% with 100% FiO2. Within half an hour of intubation, fetal bradycardia was noted. The patient was taken up for an emergency Caesarian section. At birth, the child did not cry and received two cycles of CPR and positive pressure ventilation and was shifted to the NICU. The baby was extubated after days. Postpartum the mother required 70% FiO2 to maintain 90% saturation which further improved upon proning. The Pplat and inturn the driving pressure improved upon Cesarian section. Patient required one more round of proning on D5 of ICU stay. During the course of hospitalization, the patient had one episode of septic shock and 2 episodes of urosepsis. This was treated appropriately with antibiotics. Bedside sonography revealed right-sided Hydro Uretero Nephrosis which was tackled with DJ stenting. On day 11 of ICU stay, patient was tracheostomised. By the end of 1 month, the mother was decannulated and discharged. Discussion: Pregnancy especially in the final trimester causes changes like reduced functional residual capacity and compliance. Airway edema in pregnancy complicates intubation making it difficult. Proning though not contraindicated may be difficult to achieve in pregnant patients. In our patient, we could prone the patient postpartum with ease. Though Caesarian section was done in view of fetal distress. But postpartum it was easier to ventilate the patient and oxygenation showed steady improvement. AJOG also suggests that a Caesarian section may be considered after 34 weeks in a critically ill COVID-19 patient. We also had the luxury of a neonatal ICU and the neonate could be saved though the mother's well-being was our priority. Pregnancy and gestational diabetes mellitus and receiving steroids made the patient susceptible to multiple infections which we handled by source control and antibiotics. Conclusion: Though the pandemic is on the decline this case report is an attempt to throw light on the management of the critically ill pregnant patient with ARDS. Cesarean section may aid in the management of the pregnant patient with severe ARDS.

Minimal Change Disease Relapse After SARS-CoV-2 Booster Vaccine

Immune dysregulation has been postulated as a pathogenetic mechanism for minimal change disease (MCD) and several vaccines have been reported to act as a trigger for relapse. While cases of both de-novo MCD and MCD relapse have been reported following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mRNA vaccinations, we report, to the best of our knowledge, the first case of MCD relapse following booster dose of Pfizer-BioNTech SARS-CoV-2 vaccine. 63-year-old Italian male, with history of nephrotic syndrome secondary to kidney biopsy proven MCD, who had achieved complete remission with steroid therapy, had follow up labs done that showed spot urine protein: creatinine of 10.1 and albumin of 3.0g/dL. He had received the booster dose of Pfizer-BioNTech SARS-CoV-2 vaccine 2 weeks ago, and endorsed generalized weakness, puffiness over face, edema over upper extremities that appeared within a week after administration of the vaccine, and weight gain of 10 lbs over past week. Blood pressure was elevated (152/78 mmHg). He denied any recent infections, use of Nonsteroidal Anti-Inflammatory Drugs, or antibiotics. Other diagnostic work up revealed hypertriglyceridemia, normal serum creatinine. Serological work up for secondary causes of glomerular diseases was negative. He was initiated on oral prednisone therapy. Spot urine protein:creatinine decreased to 1.1, 2 weeks after initiation of steroids. Vaccination is a recognized trigger for relapse of nephrotic syndrome. mRNA vaccines are expected to produce a higher antibody response as well as increased production of cytokines and chemokines. This can lead to dysregulation in permeability factors that can result in relapsing glomerulonephritis. As data on adverse effects of SARS-CoV-2 vaccines continue to evolve, we suggest to closely monitor patients with history of nephrotic syndrome for relapse after receipt of the SARS-CoV-2 vaccine, including the booster dose. Further studies are needed to determine whether relapse of MCD is specific for SARS-CoV-2 mRNA vaccination and to decipher mechanisms for possible immune dysregulation in those patients. This may help in formulation of protocol for vaccination in patients with nephrotic syndrome and contribute to informed decision making.

Scleroderma Renal Crisis and COVID—Is There an Association?

Scleroderma renal crisis (SRC) is a rare but potentially devastating complication of systemic sclerosis as it is associated with significant morbidity and mortality. We present an interesting case of a patient who developed SRC following infection with COVID-19. A 37-year-old female presented with new-onset hypertension, AKI, anemia and thrombocytopenia. She had a history of diffuse cutaneous systemic sclerosis diagnosed 8 years ago, that had been well controlled with immunosuppression. The patient had contracted COVID-19 infection about 2 weeks ago but had remained largely asymptomatic except for a sore throat. Urinalysis revealed sub-nephrotic proteinuria but was otherwise bland. Peripheral blood smear was notable for 12-15 schistocytes per HPF. ADAMTS13 and complement levels were normal. Serologies for ANA, ANCA, anti-Scl70, anti-Jo1, anti-Sm, lupus anticoagulant, anti-beta2-glycoprotein I, anti-RNA polymerase III, RF, cryoglobulin, RPR, hepatitis and HIV, all returned negative. Renal biopsy revealed an arterial predominant thrombotic microangiopathy (TMA) (Figure) consistent with a diagnosis of SRC. The patient was treated with anti-hypertensives including an ACE-inhibitor, but her AKI continued to worsen, ultimately leading to dialysis dependence. SRC classically develops in patients with early or progressive diffuse cutaneous disease or positivity for anti-RNA polymerase III antibodies. Our patient did not have any such risk factors and rather developed SRC following infection with COVID-19. COVID-19 has been reported to cause TMA by inducing immune dysregulation via an overactive complement system. It is plausible that infection with COVID-19 triggered an exaggerated immune response, in turn leading to the development of SRC in our patient. COVID-19 may trigger SRC in patients with systemic sclerosis in the absence of other risk factors. (Figure Presented)

CLINICAL EVALUATION OF IMMUNOLOGICAL AND CLINICAL RECURRENCE OF IMMUNE-MEDIATED NEPHROPATHIES AFTER SARS-COV-2 VACCINE

BACKGROUND AND AIMS: The mass vaccination for COVID-19 has raised new concerns for patients with immune-mediated nephropathies: there is a small but growing literature of case-reports linking SARS-CoV-2 vaccines with heightened off-target immune responses leading to De novo or relapsing glomerular diseases [1, 2]. Aim of this study was to evaluate how many and how severe were the relapses of immune-mediated nephropathies after the SARS-CoV-2 vaccine in a single center. METHOD: This is a retrospective study held in Italy from the start of the vaccination campaign (late December 2020) to December 31st 2021. We included all patients with an immune-mediated nephropathy (either on or off immunosuppressive therapy-IS), excluding patients with an end-stage renal disease or kidney transplant. In Italy we used mRNA (Comirnaty by Pfizer-BioNTech or Spikevax by Moderna) or adenoviral vector vaccines (Vaxzevria by AstraZeneca or Janssen), without any preference for patients with kidney disease, but those on active IS were given preferentially an mRNA vaccine. There was no active surveillance of lab tests after vaccination and post-vaccine tests were either concomitant to programmed visits or suggested on a patient by patient basis. Recurrence was defined as relapse of nephrotic or nephritic syndrome, doubling of urinary proteins with a max value > 1 g/24h, acute kidney injury with an active urinary sediment, or positivization or 5-fold increase of serological markers of disease activity (i.e.: ANCA in AAV). RESULTS: A total of 38 patients (M: F 28:10, age at vaccine 45.9 ± 19.1 years) completed the vaccination protocol: among them, the most common nephropathy was membranous nephropathy (n = 12, 31.6%), followed by IgA nephropathy (n = 7, 18.4%), minimal change disease (n = 6, 15.8%) and ANCA-associated vasculitis (n = 6, 15.8%);26 patients (68.4%) had at least one other comorbidity. We observed six relapses (4 MN, 1 IgA, 1 AAV), of which only one (MN) developed a mild oedema. The mean time from the first vaccine dose to the relapse was 101 ± 71 days (5-199 days) and only two episodes occurred within 4 weeks from a vaccine dose. We could not find an association between recurrences and maintenance IS at the time of vaccine or any other variable. The overall post-vaccine incidence rate of relapses was 35.8/100 patient-years, as compared with 14.0/100 patient-years historically observed in the same cohort [IRR 2.55, 95% confidence interval (CI) 0.89-5.97]. CONCLUSION: Relapses of immune-mediated nephropathies are not common after SARS-CoV-2 vaccine and we did not observe any clinically relevant relapse. However the overall rate of relapse seems to be a little higher than prior vaccination [3], but only 2/6 patients recurred soon after a vaccine dose. As these relapses seem to be self-limiting, a post-vaccine monitoring could be useful in patients at high risk of severe disease.

DE NOVO DOUBLE GLOMERULOPATHY (MEMBRANOUS NEPHROPATHY, MN AND COLLAPSING FOCAL SEGMENTAL GLOMERULOSCLEROSIS, CFSGS) ASSOCIATED TO POSITIVE MYELOPEROXIDASE-O (MPO) ANTIBODY FOLLOWING PFIZER - BIONTECH MRNA VACCINATION COVID 19

BACKGROUND AND AIMS: In the COVID 19 pandemic era, anti SARS-CoV-2 vaccination showed high efficacy at preventing the infection and its most severe complications. The aim of this report is to describe an unusual double glomerulopathy related to anti SARS-CoV-2 vaccination and the good results obtained with the immunosoppressive treatment. METHOD: An 80-year-old caucasian woman developed a nephrotic syndrome, progressive renal insufficiency and microhematuria. The patient presented a medical history of thrombocytopenic purpura treated and resolved by steroids in 2013, hypothyroidism, hypertension, ischaemic heart disease treated with surgical bypass in 2019 and pacemaker in 2020 for atrial ventricular block. Due to pandemic COVID 19 status, she received two doses of the Pfizer BioNTech mRNA COVID-19 vaccine in March 2021. Two weeks after the second dose her weight increased of 23 kg. The family physician added furosemide to her therapy for generalized edema with no diuretic effect. In April, creatinine was 1.38 mg/dL (versus 0.8 mg/dL 1 year before);urinalysis showed proteinuria (300 mg/dL) and microscopic hematuria;serum total cholesterol level was 218 mg/dL and triglycerides 178 mg/dL;then it was suggested to increase the doses of furosemide. In May 2021, creatinine resulted 2 mg/dL, serum albumin 2 g/dL, and urinalysis confirmed proteinuria and microscopic hematuria;proteinuria was 10 g/day. Abdomen ultrasound showed normal liver, kidneys and spleen, not ascites. Lower limb eco-Doppler showed right superficial femoral artery stenosis of 60% and absence of venous thrombosis. The physical examination evidenced anasarca. The patients were admitted to the nephrology unit;hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus antigen and antibody were negative. Both complement C3 and C4 levels resulted within the normal range. Cryoglobulins were absent. Urinary Bence Jones, antinuclear antibody (ANA), anti-extractable nuclear antigen (ENA), anti-double stranded DNA (nDNA) antibodies were negative. Antineutrophil cytoplasm antibodies (ANCA) were 1:2560 with Perinuclear pattern and anti-MPO positivity (716 UA/mL);anti-proteinase-3 antibodies (PR3) were negative. Antiphosholipase A2 receptor antibody (PLA2R Ab) was positive with high titre. A kidney biopsy was performed showing a double nephropathy: a focal segmental glomerulosclerosis (FSGS) with some collapsing features, superimposed on membranous glomerulonephritis (Fig. 1). RESULTS: We started the Ponticelli regimen (alternate months steroids and cyclophosphamide). After the first month of therapy, blood tests revealed creatinine 1.7 mg/dL, haemoglobin 11.7 g/dL;serum albumin 2.7 g/dL and urinalysis without microscopic haematuria. At the third month of therapy, the patient developed atrial fibrillation and started anticoagulation;blood tests were as follows: creatinine 1.1 mg/dL, serum albumin 3.0 g/dL, Ab anti-MPO 7 UA/mL and PLA2R Ab was absent. A left ocular, frontal and parietal herpes zoster induced a short discontinuation of therapy and responded well to Acyclovir;then we concluded the fourth month of therapy. At the fifth month, a SARS CoV 2 RT PCR unexpectedly resulted positive;the patient remained asymptomatic, but we stopped definitively the therapy. One month later, blood tests showed: creatinine 1 mg/dL, serum albumin 4 g/dL, proteinuria 0.7 g/die, MPO 2 UA/mL and PLA2R Ab absent. CONCLUSION: To our knowledge, this is the first case of nephrotic sindrome secondary to a De novo MN and FSGS, associated with positive MPO antibody, following Pfizer-BioNTech mRNA vaccination COVID 19;the patient responded well to immunosoppression going in remission and regaining renal function. (Figure Presented).

GLOMERULOPATHIES AFTER COVID-19 VACCINATION. REPORT OF CASES IN OUR CENTRE

BACKGROUND AND AIMS: After the start of the vaccination campaign against the SARS-COV-2 pandemic, it is possible that the number of cases of De novo and relapsing glomerulopathies will increase. So far, most of the publications related to post-vaccination minimal change disease (also associated with other vaccines against influenza virus, hepatitis B, pneumococcus, etc.) and IgA nephropathy. However, post-vaccination cases of membranous nephropathy, ANCA vasculitis or anti-glomerular basement membrane glomerulonephritis are anecdotal. Likewise, there are no cases of segmental and focal glomerulonephritis published in the literature. We present the cases that have appeared in our centre in order to support the theory of a more than probably causal relationship. We highlight two cases of focal and segmental glomerulonephritis, making this publication the first to report this pathology post-vaccination. METHOD: We present a total of 8 cases reported in our centre since the start of the vaccination campaign. We only considered cases that started with symptoms within 1 month after the first or second dose of the SARS Cov2 vaccine. Histological diagnosis was obtained in four patients with De novo glomerulopathy. In the other four patients with a flare of their baseline disease, renal biopsy was not performed. In these patients, the diagnosis of recurrence was made on the basis of laboratory and clinical data. RESULTS: Five patients of the total that appeared in our centre developed minimal change disease (4 of them were recurrences and 1 De novo), 2 cases of De novo focal and segmental glomerulomephritis and 1 case of De novo IgA nephropathy. Nephrotic range proteinuria and macroscopic haematuria were the most frequent symptoms in our patients and completely reversed after immunosuppressive treatment or, in some cases, with supportive care. All of them received mRNA-based vaccines (six patients with Pfizer and two with Moderna). The mean time to onset of symptoms after vaccination was 13 days. There was no difference in sex and the mean age was 40 years. CONCLUSION: The development of vaccines has been a key factor in the control of the SARS Cov-2 pandemic. The cases reported so far are minimal, compared with the millions of doses administered, so the benefits exceed the risks. However, according to the literature, we recommend closer follow-up in patients with known glomerulopathies and to perform renal biopsy as soon as possible after the onset of symptoms related to post-vaccination renal disease. In our centre, most of the cases appeared after the first dose of vaccination and we induced the administration of the remaining doses because all our patients did well with treatment. However, we suggested that one option might be to delay, but not to stop, the second dose in order not to interfere with the immune response to vaccination in patients who are receiving immunosuppression.

DE NOVO GLOMERULONEPHRITIDES FOLLOWING BNT162B2 COVID-19 VACCINE: A CASE SERIES

BACKGROUND AND AIMS: The development and massive use of mRNA COVID- 19 vaccine BNT162b2 has raised new concerns on triggering De novo immunemediated diseases, in particular rare diseases as glomerulonephritis (GN), even if the security profile is excellent and severe reactions have been rare. In literature few similar cases were recently described [1, 2]. We report six cases of newly diagnosed GN after a two-dose regimen of SARS-CoV-2 vaccine, from a single tertiary care institution in Northern Italy. METHOD: We described six cases of De novo GN occurring after massive use of Pfizer-BioNTech BNT162b2 COVID-19 vaccine from March 2021 to December 2021. All cases were biopsy proven. Baseline characteristics and laboratory findings, treatments and outcomes were based on review of medical records. RESULTS: From April 2021, we observed two IgA nephropathies (IgA-N), one membranous nephropathy (MN), one membranoprolipherative GN (MPGN), one acute interstitial nephritis (aTIN) and one minimal change disease (MCD). Of note, one IgA-N presented with diffuse purpura as in IgA-vasculitis. The median age at vaccination was 52.8 years (min-max 18-67) and three (50%) were female;arterial hypertension was the most common comorbidity (50%). Only one subject contracted COVID-19 before vaccine (16.6%). None of the points showed any sign of renal disease before vaccine;at the time of disease onset, the median creatinine was 1.49 mg/dL (min-max 0.6-10.5 mg/dL) and proteinuria 3.0 g/24 h (min-max 0.9-13.8 g/24 h). All cases presented after the second dose (1 day to 6 months thereafter) and three (50%) were within 3 weeks from the vaccine. Of note, the aTIN developed after the vaccine during a long-time therapy with statins and relapsed after a rechallenge with a statin few months later. All the nephropathies were treated as per center practice, with an overall good response (four partial remissions and one complete remission). Given a target population of about 100 000-200 000 residents in our area, we could estimate an incidence rate of 4-8 cases/100 000 patient-years. CONCLUSION: This small series has a lot of limitations including the small number of patients and we probably missed some cases in our area. Furthermore, we could not investigate a causal association, even if the timing of disease onset might be suspicious in three cases and the incidence seemed to be almost twice as the expected in Europe (about 2-4/100.000 patient-years). As for SARS-CoV-2 vaccines, it is likely that the mRNA vaccine will result in a more potent inflammatory stimulus than the one observed after inactivated virus-vaccine: maybe some patients had already a subclinical GN and the vaccine constituted a flare leading to the full-blown disease [3].

MINIMAL CHANGE DISEASE SECONDARY TO SARS-COV-2 (COVID-19) INFECTION: A REPORT OF 2 CASES AND REVIEW OF RELATED LITERATURE

BACKGROUND AND AIMS: The COVID-19 pandemic has brought to the forefront a wide spectrum of renal injuries that included glomerulopathies, some of which were recently highlighted in various case reports. These consist of focal and segmental glomerulosclerosis (FSGS) and minimal change disease (MCD).1 These changes were found among seemingly vulnerable populations such as the African American and Caucasian ethnicities with paucity of reports among other races. We present two cases of biopsy-confirmed MCD secondary to COVID-19 infection among adult Filipino patients. METHODS: Case Report RESULTS: Case 1 A 40-year-old Filipino female with a history of right total mastectomy 2 years prior for a low-grade phyllodes tumor and no other medical comorbidities was admitted due to stillbirth. She was noted to have bipedal edema with a positive COVID-19 RT-PCR swab. Further workup revealed a serum creatinine 1.04 mg/dL, urine RBC 1/HPF and a 24-h urine protein of 9.22 g with hypoalbuminemia and dyslipidemia. Serologic workup was noted to be negative. She was started on Losartan, Atorvastatin, and Furosemide. A kidney biopsy was performed which demonstrated unremarkable light microscopy and immunofluorescence and widespread podocyte-foot process effacement. These biopsy findings were interpreted to be consistent with minimal change disease. She was started on Prednisone at 1 mg/kg/day with continuation of both Losartan and Atorvastatin. Six weeks after, the patient achieved complete remission with resolution of both hypoalbuminemia and dyslipidemia. She also reports no further recurrence of edema. Case 2 A 61-year-old Filipino male with a history of type 2 diabetes mellitus, hypertension, dyslipidemia and mild COVID-19 infection 4 months prior now presented with diarrhea. A routine COVID-19 RT-PCR swab revealed a re-infection. Physical examination noted bipedal edema. Further workup demonstrated a serum creatinine 3.39 mg/dL, urine RBC 2/HPF and urine ACR 2.6 g/g. Serologic tests were negative. He was diagnosed with Nephrotic Syndrome and underwent kidney biopsy. Findings showed an unremarkable light microscopy and immunofluorescence with widespread podocyte-foot process effacement. These findings were found to be consistent with minimal change disease and acute tubular injury. He was started on Prednisone (1 mg/kg/day), Losartan, Furosemide and Atorvastatin. Eight weeks later, the patient achieved complete remission with resolution of edema. CONCLUSION: It is currently suspected that APOL1 risk variants found in reported cases of COVID-19-associated glomerulopathies are underlying toxic gain-of-function mutations that drive kidney disease.2 It is interesting to note that APOL1 renal risk variants are found exclusively in African-derived chromosomes and are rarely found among European or Asian chromosomes.3 Even though an APOL1 genotyping was not performed, our case reports provide the first examples of MCD among individuals without a high-risk genotype (APOL1) by epidemiology and enlarge the literature on MCD in COVID-19. We posit that there may be other underlying predispositions or mechanisms that may be driving glomerulopathy formation among COVID-19 patients aside from their inherent APOL 1 risk. Both of our patients were started on steroid therapy with a tapering regimen and achieved complete remission on subsequent follow-up. Existing reports suggest that most cases of COVID-19-associated MCD will often achieve resolution of AKI and proteinuria with steroid therapy, even in those with high-risk APOL1 genotype, emphasizing the need for an accurate histologic classification.4 (Figure Presented).

A CASE OF FSGS IN A PREVIOUSLY HEALTHY MALE AFTER THE SECOND DOSE OF COVID-19 MRNA VACCINE

Case Report Background COVID-19 infection and COVID-19 mRNA vaccines have been associated with the occurrence of de-novo and relapsing glomerulopathies. Although, Focal Segmental Glomerulosclerosis (FSGS) similar HIV associated Nephropathy (HIVAN) has been reported with COVID-19 infection in African American population with Apolipoprotein L1 gene mutation, amongst the few reported cases post-vaccine, Minimal change disease (MCD), IgA nephropathy (IgAN), Anti-Glomerular basement membrane glomerulonephritis (Anti GBM GN), and membranous glomerulonephritis (MGN) have been reported. Case A 26-year-old Caucasian male with a history of tobacco use complained of Frothy urine and edema for 3 weeks post second dose of Moderna COVID-19 vaccine on 06/01/21. He received the first dose on 5/04/21. On his annual wellness visit on 5/18/21, he had no complaints, normal physical examination with serum albumin 5g/dl, and urinalysis significant for trace proteinuria. A repeat urinalysis post-onset of symptoms on 7/18/21 revealed 3+ proteinuria, no RBCs, 24- hour urine revealed 3.2g proteinuria. Further investigations revealed Hypoalbuminemia (2g/dl), persistent proteinuria, and an unremarkable renal ultrasound, ANA, ANCA, Anti-dsDNA, Anti-PLA2R, anti-streptolysin, RF, HIV, hepatitis panel, and serum complement levels. Renal biopsy revealed Tip lesion variant of FSGS with 100% effacement of podocyte foot process. Therapy with Prednisone 60 mg daily was initiated, following which an improvement in edema and serum albumin levels (2.7 g/dl) were noted. Discussion A few de-novo cases of anti-GBM GN, ANCA positive vasculitis, MCD and IgAN, and relapsing cases of IgAN, MCD, MGN, and Thrombotic microangiopathy have been reported post-COVID 19 mRNA vaccination. Most reported cases of MCD occurred after the first dose whereas IgAN flare-up occurred after the second dose. Our case is unique as our Caucasian patient developed FSGS post-second dose of Moderna vaccine. Although the pathogenesis is unclear, it is thought to be related to an acute T-cell immune response involving cytokine production to COVID 19 spike protein which is responsible for inducing or worsening existing podocytopathies. Interestingly fewer cases have been reported following adenovirus vector or inactivated virus vaccination. Most of the reported cases of IgAN flare-up have been mild and a small number of MCN cases required ICU admission for management of fluid overload. As observed in a few prior case reports our patient had a slow response to steroid therapy. Although guidelines on COVID 19 vaccination in patients with existing glomerulopathies remain unclear and are based on case-by-case scenarios, the benefit of COVID 19 vaccination, may in general, outweighs the risk of glomerular diseases. We encourage further studies on this topic, especially in the era of booster doses with ongoing discussion about mixing two types of vaccines.

Idiopathic nephrotic syndrome: a clinical approach

Children with new-onset nephrotic syndrome invariably present to general paediatrics in the first instance. Many with known nephrotic syndrome under the care of a paediatric nephrologist will present to local services with complex relapses. Using a case-based approach, this review aims to equip the general paediatrician with the skills: to assess and manage a child with a new presentation of nephrotic syndrome, to identify the complications associated with the nephrotic state, to choose the most appropriate steroid regimen and to identify those patients who should be referred to a paediatric nephrologist. We focus on the management of steroid-sensitive nephrotic syndrome (SSNS), the most common diagnosis in children presenting with nephrotic syndrome. We also discuss aspects of management of nephrotic syndrome relevant to the COVID-19 pandemic. Additionally, by the end of the article, the reader should have a basic understanding of the underlying pathophysiology of nephrotic syndrome and its resultant complications.

POS-115 MINIMAL CHANGE DISEASE IN A HEALTHY WOMAN WITH TOXICODENDRON TOXICITY

Introduction: Minimal change disease (MCD) is a major cause of idiopathic nephrotic syndrome (NS) which is composed of heavy proteinuria, hypoalbuminemia, and edema. It represents 15% of idiopathic NS in adults and the proportion of cases decreases with age as other entities such as membranous nephropathy become more common. Kidney damage associated with Toxicodendron species toxicity is quite rare but there are three lesions already described: proliferative glomerulonephritis, arteritis and membranous nephropathy. Here we report a case of MCD associated to Toxicodendron toxicity. Methods: A 47 year old mexican woman with no history of chronic diseases was referred to the nephrology office. She has a positive familiar history for diabetes and hypertension and she was recently vaccinated for COVID-19. She was referred for proteinuria incidentally found during routine tests three months ago which has been persistent on urinary testing afterwards, she recalls a Toxicodendron spp (poison ivy) exposure which led to an self-limited dermatitis 5 days before the first urinary test was taken. Initial workup showed 3.54 gr/24h proteinuria, hypoalbuminemia (3.2 gr/L) and hypercholesterolemia (256 mg/dl) and a nephrotic syndrome diagnosis was made. Further testing included negative HIV, HCV and HBV serology, normal C3 and C4 levels and negative anti-PLA2R, P-ANCA, C-ANCA, antinuclear antibodies. Normal kidneys were visualized on ultrasound. A kidney biopsy was performed and reported a minimal change disease. Steroid glucocorticoids was administered with methylprednisolone for three days and she was discharged with oral glucocorticoid for maintenance. On ambulatory follow up the patient had a dramatic improvement of the proteinuria. Results: A 47 year old woman developed proteinuria a few days after ivy poison exposure with a subsequent nephrotic syndrome. Renal biopsy shows a minimal change disease and good glucocorticoid response was met. Conclusions: Our hypothesis is that ivy poison exposure is directly involved in MCD onset in this patient. No conflict of interest

POS-872 Post covid vaccination- new onset glomerulonephritis- a mere co incidence or a impending reality??

Introduction: India is world’s second most populous country with tropical climate and highly dense overcrowded areas which make it an easy target for spread of covid infection. As a preventive measure the government of India launched a vaccination drive from 16th January 2021, currently as of September 2021 more than 806 million doses of the approved vaccine- (covishield- astra Zeneca and covaxin- bharat biotech) have been given. They are both adenovirus carrying viral load and inactivated vaccine respectively. Methods: We will now describe a series of 7 cases of immunogenic glomerulonephritis response following covid vaccination which have been admitted in our tertiary care hospital in southern India between a period of January 2021- September 2021 with signs and symptoms of any of the following nephrotic/ nephritic syndrome, rapidly progressive glomerular disease, isolated proteinurea, hematuria, acute kidney injury and thrombotic complications. All these patients had a similarity in common- all had received single/ 2nd dose of covid vaccine in the last 15 days before the onset of symptoms. All Patients underwent renal biopsy for histological confirmation of the diagnosis as well as covid antibody level testing to see for any relation between the two. once diagnoses was confirmed patients were started on immunosupression in form of steroids, plasmapheresis and other supportive measures like ACE/ ARBs.their outcomes were recorded serially as to whether complete/ partial or no remission was achieved. Results: [Formula presented] All characteristics of the patients including the baseline characteristics- complete blood picture, serum creatinine, electrolytes, 24 hour urine proteinurea. The vaccine type and duration of appearance of symptoms,the renal biopsy findings, the management of each patient and their outcome have been described in the table attached. we had case series of 7 patients with different presentation of glomerulonephritis in the past 9 months with a history of temporal association with covid vaccination in last fortnight. Conclusions: The Immunonephrology Working Group of the ERA-EDTA recently published recommendations on the use of COVID-19 vaccines in patients with autoimmune kidney diseases and supports the vaccination of all individuals without known contraindications. However, these recommendations did not advise on whether vaccination with one vaccine platform was preferable to another. Vigilance should be exercised in patients presenting with new-onset urinary abnormalities and hypertension following COVID-19 vaccination.Besides urinary tract infection and urological causes,glomerulonephritis should be considered in patients with non-resolving macroscopic hematuria. Proteinurea and active sediments in urine. Meanwhile, these isolated reports should not lead to vaccine hesitation during this pandemic as the benefits of vaccination strongly outweigh potential risks. No conflict of interest

Minimal change disease (MCD) after Moderna COVID-19 vaccination

Background: Post vaccination minimal change disease with nephrotic syndrome and acute kidney injury has been reported after influenza and Pfizer-BioNTech vaccine. Further research is needed to prove a correlation. Methods: Clinical case, renal biopsy, dialysis Results: We present a case of a 65 years old patient, who developed minimal change disease 8 days following first injection with Moderna COVID-19 vaccine. In his medical history the patient has collagenous colitis and was on treatment with budenofalk. He presented with full blown nephrotic syndrome and developed dialysis dependent acute kidney injury for two weeks. Renal biopsy showed minimal change disease with 90% loss of podocyte processes in electron microscopy. Two weeks of dialysis and immunosupressive therapy over three months after the event lead to recovery of renal function to baseline. The patient received the second COVID-19 vaccination without developing complications or relapse. Conclusions: We present one of the first patients with minimal change disease after Moderna COVID-19 vaccine. There was an association between the timing of the vaccination and clinical manifestation of ne-phrotic syndrome. A definite causal relation still needs to be elucidated. A possible pathomechanism would be, that mRNA vaccines initiate T-cell mediated injury. However further studies are needed to find the im-munological mechanism of action after COVID-19 vaccination. Out of many millions of mRNA vaccines administered so far, to our knowledge, 7 cases of de novo minimal change disease have been described as well as up to 17 other glomerular diseases de novo and relapsing after COVID-19 vaccination.