Minimal Change Disease Secondary to Either COVID-19 Infection or Pfizer-BioNTech COVID-19 Vaccination

Introduction/Objective Kidney injury has now become one of the known complications following COVID-19 infection and vaccination. Only few cases of minimal change disease following administration of COVID-19 vaccination and infection have been reported. This study was to highlight incidence of minimal change disease following COVID-19 infection or vaccination. Methods/Case Report Case 1:15 year-old female with past medical history of asthma and hypercholesterolemia presented for evaluation of periorbital edema, nephrotic-range proteinuria, hypoalbuminemia, elevated serum creatinine, elevated blood pressures, and hematuria after COVID-19 infection. Renal biopsy after 1 week of infection showed unremarkable glomeruli and negative immunofluorescent stains in glomeruli, and 20-30% fusion of foot processes. The biopsy was consistent with a minimal change disease with features of natural remission (her nephrotic-range proteinuria resolved soon after). Case 2: 18 year-old female with no significant past medical history presented with a chief complaint of generalized swelling, which started around the same time she received her 1st dose of Pfizer COVID vaccine (the 2nd dose 2 months later). She had a nephrotic range proteinuria and hypoalbuminemia, but normal level of serum creatinine. A renal biopsy after 4 months of vaccination showed unremarkable glomeruli by light microscopy, negative immunofluorescent study, but diffuse effacement of foot processes involving more than 80% of the examined loops by electron microscopy. This biopsy findings were consistent with a minimal change disease. Both patients did not receive any treatment before the renal biopsies. Results (if a Case Study enter NA) NA Conclusion Minimal change disease can be a rare complication following COVID-19 infection or Pfizer COVID-19 vaccination, raising a question if there are similar antigens induced by the infection or by the vaccination that trigger the minimal change disease. Further studies are needed to determine the incidence and pathophysiology of minimal change disease either post COVID-19 vaccines or following COVID-19 infections.

SPANISH NATIONAL REGISTRY OF BELIMUMAB IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

BackgroundBelimumab (BLM) is a monoclonal antibody that inhibits B-lymphocyte stimulating factor (BlyS) approved as a specific treatment for systemic lupus erythematosus (SLE) in 2011. We present the experience with BLM in a Spanish cohort with more than 460 patients.ObjectivesTo describe demographic characteristics, efficacy and safety of BLM in patients with SLE in Spanish population since its approval.MethodsDescriptive, retrospective, multicenter study in patients diagnosed with SLE according to EULAR/ACR 2019, SLICC and/or ACR 1997 diagnostic criteria. Data regarding SLE patients treated with BLM were collected from medical records (2011-2022). Demographic features, efficacy, laboratory variables, SLEDAI, renal involvement, steroid dose, administration routes and safety were assessed. To see whether a trend in BLM prescription had changed or not over time, two periods of time were analyzed: 2011-2016 (period1) and 2017-2022 (period2).ResultsBaseline characteristics of patients are summarized in Table 1.A total of 462 patients (36 hospitals) were included, 50.9% were on intravenous (IV), 34% on subcutaneous (SC) and 15.1% switched from IV to SC route. The median number of pre-BLM csDMARD use was 2.0 (2.0-3.0), being hydroxychloroquine (HCQ) the most frequently used (94.5%). Fifty-two patients were treated with IV cyclophosphamide with a median of 6 bolus received. At the time of BLM start, 443 patients were on prednisone with a median dose of 6.2 mg (5.0-10.0). Significant decreases in prednisone dose, SLEDAI and anti-DNA antibodies were observed from baseline until the last visit, whereas complement C3 and C4 values raised (Figure 1). A total of 118 patients (27.4%) had renal involvement with a median proteinuria of 1.0 g/day (0.5-2.4). Renal biopsy was done in 102 out of 118 patients, being class IV (33%), class III (21%) and class V (16%) the most frequently reported. After BLM, 73.3% of these patients improved (median proteinuria of 0.2 g/day (0.1-0.7).In period1, 100 patients started BLM compared to 362 in period2. The median time from SLE diagnosis to BLM begin was 7.1 (4.0-13.7) and 6.2 (2.1 -14.4) years in period1 and period2, respectively (p=0.454). We found a trend to use more csDMARD before BLM treatment in period1: 2.5 (2-3) vs. 2 (2-3) (p=0.088).A total of 143 (30.5%) patients discontinued treatment mostly due to inefficacy (55.9%) and infections (11.9%). In fact, 116 patients developed infections, mostly mild;2 patients died, 16 had COVID-19 and 4 patients developed tumors requiring discontinuation of the drug.ConclusionIn our cohort of SLE patients in a real-world setting, BLM has been effective, safe and seems to be a good choice to treat renal involvement.References[1]Navarra SV, Guzmán RM, Gallacher AE, et al. Lancet. 2011;377(9767):721-31.[2]Stohl W, Hiepe;rt al. Arthritis Rheum. 2012;64(7):2328-37.[3]Furie R, Rovin BH, Houssiau F, et al. N Engl J Med. 2020;383(12):1117-1128.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Haematuria and proteinuria associated with COVID-19-mRNA-vaccination: a case-report

Objective: A new generation of vaccine technology platform has been developed to combat the COVID- 19 pandemic, the mRNA vaccine. The EMA granted the Pfizer- BioNTech COVID-19 vaccine an emergency use authorization in December 2020 with limited clinical experience, especially in the pediatric population. Method(s): Here, we present a case-report of a 17-yearold girl, who was vaccinated with the mRNA-COVID vaccine in October 2021, and developed a gross hematuria and proteinuria the day after the vaccination. Result(s): The patient presented at our outpatient clinic three days after the vaccination with new-onset hematuria and proteinuria. Up to this date, she had no former known medical conditions and the family history was negative regarding kidney diseases. We excluded nephrolithiasis, autoimmune glomerulonephritis and urinary tract infection as causes. The laboratory chemistry of the kidney was within normal range. The proteinuria dissolved spontaneously, and a microhematuria persisted. One day after the second dose of Cominarty in November 2021, the gross hematuria with proteinuria relapsed. A treatment with an ACE-inhibitor did not have any effect on the proteinuria. At this point, only a few casereports of patients with a comparable clinical course, especially from Japan, were published. In suspicion of a vaccine-triggered nephritis we started a prednisolon therapy which dissolved the proteinuria and induced a regression of the haematuria to a minimal stage. Conclusion(s): Within the last year, the medical community has gained more insights concerning mRNA vaccines. There is growing evidence, that mRNA vaccines can trigger de novo or relapse IgA nephropathy. But more systematic research and long-term evaluation is desirable to elucidate the underling pathophysiology as well as the influence on kidney survival of affected patients in the future. Furthermore, patient education should incorporate the risk of hematuria and proteinuria in children when applying mRNA vaccines.

TIME MANAGEMENT AND RISK FACTORS IN LIFE-THREATENING ANCA-VASCULITIS

BackgroundAccuracy of diagnosis and prompt therapeutic intervention are the mainstay in patients with ANCA-associated vasculitis(AAV) suffering from life-threatening complications [1].However, there is no definition of therapeutic window in vital AAV, nor its impact on patient outcome regarding length of hospital stay, intensive care unit(ICU) admission or survival.ObjectivesThe aim of the study is to analyze the process of care from the perspective of time management in vital organ involvement AAV patients and to identify potential risk factors for ICU admission.MethodsA retrospective multicenter study identified AAV patients with life-threatening organ involvement, defined as alveolar hemorrhage, rapidly progressive renal failure, myocarditis and cerebral granuloma. Demographic data was collected. Key time frames were recorded, namely the interval from acute symptom onset to hospital presentation, days until imaging(plain X-ray, cardiac ultrasound, CT-scan), time to therapeutic intervention with corticosteroids or biologic/non-biologic immunosuppression(cyclophosphamide or rituximab) and to renal replacement therapy(RRT) or plasmapheresis. Time to ICU admission, hospital length-of-stay, Birmingham Vasculitis Activity Score(BVAS) were also noted. Statistical analysis was performed using SPSS and Chi-square and Pearson correlation tests were applied.Results66 patients with AAV were enrolled, out of which 17 fulfilled inclusion criteria. Mean age in the study group was 58.6±11.1 years old,10 patients(58.8%) were females and 7 (41.2%) males.11(64.7%) patients were c-ANCA positive, while 6 (35.3%) had p-ANCA and all were diagnosed with AAV prior to life-threatening event. Two patients had COVID-19 triggered AAV.In the study group, the most frequent critical organ suffering was rapidly progressive renal failure(12), followed by alveolar hemorrhages(10), 2 cerebral granulomas and one acute myocarditis. Three patients(17.6%) had more than one vital manifestation. Ten patients(58.8%) had more than three additional non-organ-threatening manifestations. Mean interval from AAV diagnosis to emergency admission was 30.1± 61.1 days, median 3 and from severe episode onset to hospitalization 1.65±0.18 days, median 1. There was only one death in the study group. Three patients were admitted in the ICU in 0.59±1.5 days following hospital presentation and required either RRT or plasma exchange within 2.66 days. Imaging examination was performed unanimously the day upon hospital admission. All patients received corticosteroids in the first 5.95±14.3 days, while immunosuppression was given to 13(76.5%) patients within 11.5±15.5 days from hospitalization.12 patients(70.5%) suffered from associated infections. Mean BVAS(13.6±6.76) correlated to ICU admission(p 0.013, r 0.58).Patients in ICU revealed higher BVAS(22±9.53) versus non-ICU(11.8±4.76).Hospital length of stay was 14.7±10.7 days(median 14) and showed no relationship to the type of severe organ involvement. The need for ICU caring was dominant in males(p 0.05) and confirmed in patients with proteinuria(p 0.012) and at least two major organ damage.ConclusionThis study shows that severity risk factors for potential ICU admission for life-threatening AAV appear to be male gender, proteinuria and the number of affected organs.Moreover, BVAS should be considered a useful tool to predict patients' risk for intensive care management since a higher score indicates a more aggressive disease.However, time to investigational or therapeutic intervention did not correlate to patient outcome in AAV.References[1]Geetha, D., Seo, P. (2011). Life-Threatening Presentations of ANCA-Associated Vasculitis. In: Khamashta, M., Ramos-Casals, M. (eds) Autoimmune Diseases. Springer, London. https://doi.org/10.1007/978-0-85729-358-9_8Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Collapsing glomerulonephritis in a COVID-19 patient. Case report

Acute renal injury due to collapsing glomerulonephritis is associated with high morbidity and mortality, requiring chronic dialysis, COVID-19 is one of its causes. A 17-year-old male patient presented with a four-month history of edema, foamy urine and reduction in the urine flow;anasarca was observed at physical examination. Laboratory values showed creatinine 4,2 mg/dl;albumin 1,9 gr/dl;cholesterol and triglycerides were high;proteinuria 6,7 gr/24h: leucocyturia and hematuria with negative urine culture. Serologies for HIV, syphilis and hepatitis were negative. Studies for systemic lupus were negative. An antigenic test for SARS-CoV-2 was positive as well as an IgG. Renal Biopsy showed Focal and Segmental Glomerulosclerosis, Collapsing variant. He received corticosteroids and cyclosporine. Creatinine improved;proteinuria remained >3 gr/24 hours.Copyright © Universidad Peruana Cayetano Heredia, Facultad de Medicina Alberto Hurtado. All Rights Reserved.

A Rare Cause of Enteritis in an Adult Male

Introduction: IgA vasculitis is more commonly seen in the pediatric population than in adults. Rarely IgA vasculitis is associated with malignancy, most commonly solid tumor malignancies, although there are case reports of association with hematologic malignancies. We report a case of large B-cell lymphoma mimicking IgA vasculitis in a 33-year-old immunosuppressed male with a prior history of IgA vasculitis. Case Description/Methods: A 33-year-old Caucasian male post renal transplant from reflux nephropathy on chronic immunosuppression was hospitalized for postprandial epigastric abdominal pain, nausea, vomiting and diarrhea. Two years prior, he was admitted for the same symptoms, palpable purpura of the lower extremities and elevated serum IgA. Enteroscopy had shown duodenal and jejunal ulceration with biopsies staining positive for IgA, confirming IgA vasculitis. He had complete resolution with a steroid taper. His current presentation had resulted in multiple hospital admissions, but empiric trial of steroids failed to alleviate symptoms. Vitals were normal and exam was notable for epigastric tenderness. Labs were notable for WBC 19.00 x103/cmm with normal differential, hemoglobin 9.2 gm/dL (prior 11.0 gm/dL), CRP 20.7 mg/L, serum creatinine 2.7 mg/dL (prior 1.5 mg/dL), and urinalysis with proteinuria, sterile pyuria, and hematuria. CTA abdomen/pelvis revealed thickening of the duodenum with shotty mesenteric lymph nodes without ischemia. Enteroscopy revealed an erythematous duodenum and jejunum (figure A). Jejunal biopsy (figure B) revealed CD20 positive cells consistent with DLCBL (figure C). He was seen by oncology and treated with R-CHOP but later unfortunately expired due to COVID-19 complications. Discussion(s): Non small cell lung cancer and renal cell carcinoma are most commonly associated with IgA vasculitis. It may also be seen in both Hodgkin and Non-Hodgkin lymphomas in adult patients. If IgA vasculitis occurs after a malignancy is diagnosed, it may indicate that metastasis has occurred. Malignancy associated IgA vasculitis is more likely to have an incomplete response to steroids and requires treatment of the underlying malignancy to achieve remission. Our case illustrates posterior probability error and premature closure cognitive biases. We should consider alternative diagnoses rather than anchor on prior diagnoses even when presentations are similar. Our case also highlights the importance of considering occult malignancy in adults with diagnosis of IgA vasculitis.

Sequential rituximab therapy sustains remission of nephrotic syndrome but carries high risk of adverse effects.

BACKGROUND: Sequential rituximab (RTX) administration has emerged as an important strategy to sustain remission of disease in patients with difficult-to-treat nephrotic syndrome. METHODS: We report the efficacy and safety of sequential therapy with two or more courses of intravenous RTX in 250 patients with difficult-to-treat steroid dependence (n = 127) and calcineurin inhibitor (CNI)-dependent or CNI-refractory steroid resistance (n = 123) managed at one center during 2015-2021. Subsets of patients were cross-sectionally tested for hypogammaglobulinemia, seroprotection against and hyporesponsiveness to vaccines for hepatitis B and tetanus, BK/JC viruria and human antichimeric antibodies (HACAs). RESULTS: Sequential RTX therapy, initiated at a median of 10 years [interquartile range (IQR) 7.3-14.4], was administered for 1.8 courses/person-year [95% confidence interval (CI) 1.7-2.0] over 2.0 years (95% CI 1.2-3.0). Therapy was associated with postponement of relapses by a median of 3 years in patients with steroid-sensitive disease and 2 years in those with steroid resistance. Relapses were reduced by a mean of 2.0 relapses/person-year (95% CI 1.8-2.2), enabling a reduction in prednisolone dose to 0.04 mg/kg/day (95% CI 0.01-0.11) and withdrawal of additional immunosuppression in 154 (62%) patients. RTX-associated adverse events, occurring at 0.20 events/person-year (95% CI 0.17-0.23), were chiefly comprised of infusion reactions (n = 108) and infections (n = 46); serious adverse events were observed in 10.8% patients, at 0.03 events/person-year (95% CI 0.02-0.05). Hypogammaglobulinemia was observed in 35% of 177 patients and was moderate to severe in 8.5% of cases. Rates of seroprotection at baseline and response following vaccination were lower for hepatitis B [1.9% and 29.4% (n = 52)] than tetanus [65.5% and 34.5% (n = 58)]. BK/JC viruria, without viremia, was observed in 7.3% of 109 cases. A total of 19 of 107 patients (17.8%) had HACAs, which were associated with B cell nondepletion and serum sickness. Age at therapy of <9-10 years was associated with a risk of early relapse, treatment failure and hypogammaglobulinemia following RTX therapy. CONCLUSIONS: Sequential therapy with RTX effectively reduces relapses in patients with difficult-to-treat steroid- and/or CNI-dependent or CNI-refractory nephrotic syndrome. Therapy is associated with high rates of hypogammaglobulinemia and infusion reactions.

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.

Evaluation of Urine L-FABP Point of Care Kit in the Philippines as Predictive Marker of Clinical Severity of COVID-19 (EPOCH COVID study)

Background: The search for simple clinical and laboratory markers to help predict the clinical severity of patients presenting with COVID-19 has prompted this study to look at the predictive value of urine L-FABP (Liver Type-Fatty Acid Binding Protein) point-of-care test kit at the initial presentation of COVID-19 patients to the hospital. Method(s): The validation study prospectively included 109 consecutive patients with mild to moderate COVID-19, mean age of 52.2 years (range 19-84) presenting at the Emergency Rooms of 4 participating Metro-Manila hospitals from February to April 2021, with available data for analysis for 103 patients. Urine L-FABP POC (Point-of-Care) test and other clinical parameters and the level of severity of COVID-19 were determined at Day 0, Day 4 and Day 7. Computations for Sensitivity, Specificity, Positive and Negative Predictive values and Likelihood ratios were performed Results: Twenty-three patients tested positive for urine L-FABP, out of the 103 patients analyzed, while 80 tested negative. Of the 23 patients who tested positive for urine L-FABP, 6 has progressed in severity, while 17 did not progressed. Of the 80 patients who tested negative for urine L-FABP, 13 progressed, while 67 did not progressed in severity. Giving a Sensitivity of 31.58%, Specificity of 79.76%, Positive predictive value of 26.09%, Negative predictive value of 83.75%. Combining urine L-FABP and initial clinical parameters like SIRS (Systemic Inflammatory Response Syndrome) criteria to predict progression of severity yielded a higher Specificity of 91.67 % and Negative Predictive value of 84.62%. Conclusion(s): The study shows the utility of initial urine L-FABP POC test as a negative screening test in triaging adult patients presenting to the ER with mild to moderate COVID-19. Patients at the ER with a negative urine L-FABP test, will most likely not progressed to severe COVID-19. Combining clinical parameters like SIRS Criteria with the urine L-FABP result can increase the negative predictive value.Copyright © The PHILIPPINE JOURNAL OF INTERNAL MEDICINE is a peer reviewed journal and a copyrighted publication of the Philippine College of Physicians.

Idiopathic anomalous congenital band causing small intestinal obstruction in a 5-month-old dog

A 5-month-old, intact male, yellow Labrador retriever was presented with a 24-hour history of anorexia and vomiting. Abdominal imaging revealed the presence of a mechanical obstruction in the jejunum and peritoneal effusion. Cytologic evaluation and culture of the effusion prior to surgery identified a suppurative exudate with bacteria consistent with septic peritonitis and suspected to be related to the intestinal lesion. An exploratory laparotomy was performed, and a segment of jejunum was circumferentially severely constricted by an off-white, fibrous band of tissue. Resection and anastomosis of the strangulated segment of jejunum and excision of the constricting band provided resolution of the clinical signs. The dog made a complete recovery. Histologic evaluation revealed the band to be composed of fibrovascular and smooth muscle tissue, consistent with an idiopathic anomalous congenital band. No other gastrointestinal lesions were observed, either grossly at surgery or histologically in the resected segment of intestine. To our knowledge, a similar structure has not been reported in the veterinary literature.Copyright © 2022 Canadian Veterinary Medical Association. All rights reserved.

WCN23-1206 Glomerulopathies Biobank in Uruguay. Description of the first 110 patients enrolled

Introduction: The incidence of glomerular diseases varies across different countries and criteria for kidney biopsy has changed over time. In Uruguay, glomerular diseases (GD) are a frequent cause of end stage kidney disease (ESKD) and renal replacement therapy with an annual incidence of 25.0 patients per million population according to data from the Uruguayan Dialysis Registry (UDR, year 2020). Since 1970, the Uruguayan Registry of Glomerulopathies has been recording the incidence, epidemiology and evolution of patients with GP in our country. In 2018, the Glomerulopathies Biobank (GB) began to operate including all patients with a native kidney biopsy performed at the Nephrology Department of the teaching hospital Hospital de Clinicas in Montevideo, Uruguay. The purpose of the BG is to record the phenotype (clinical and paraclinical) of patients with GD diagnosed by renal biopsy and at the same time store blood, urine, renal tissue and DNA samples. The aim of this report is to communicate the first 110 patients enrolled in the BG, which started in February 2018. Method(s): The BG protocol includes the collection of patronymic data, personal history, and clinical and paraclinical features of renal pathology. Plasma, urine and cell samples are stored for subsequent DNA extraction at the time of the kidney biopsy. In our country, all renal biopsies are performed by nephrologists. The Glomerular Biobank project is funded by the Nephrology Research Fund (School of Medicine, University of the Repubic) and was approved by the Ethics Committee of the Hospital de Clinicas and the Regulatory Verification Unit of the National Institute of Donation and Transplantation. The results are presented as mean and standard deviation (SD) for the continuous variables;and qualitative variables are described with percentages. Result(s): Patient recruitment began in February 2018 and we have recruited 110 patients. The mean age at the time of biopsy was 38.3+/-16.1 (min:16;max:78) years. Regarding sex distribution, the female sex slightly predominated (55.3%). Plasma creatinine was 2.1+/-1.45 mg/dL, proteinuria was 3.1+/-3.7 gr/dL and albuminaemia was 3.2+/-1.0 mg/dL. Microhaematuria was present in 61% of patients in the sediment study. Figure 1 shows the negative impact of the COVID 19 pandemic on the incidence of patients undergoing kidney biopsy. IgA nephropathy (13,8%)was the most frequent primary glomerular disease, followed by d focal and segmental glomerulosclerosis and membranous nephropathy. Consernig the glomerulopathies secondary to a systemic disease, the most frequent diagnosis was lupus nephritis (34,5%) followed by vasculitis, amyloidosis and diabetes. Conclusion(s): Having a prospective cohort of patients with glomerular disease, including reliable data and biological samples, will allow us to perform clinical and epidemiological analyses quickly and reliably in the future. The data and aliquots of biological material are available to any local nephrologist who proposes a hypothesis and has the approval of the corresponding ethics committee. The medium-term objective is to incorporate other national reference institutions in the care of patients with glomerular diseases. The data collected by the Glomerular Biobank will be a valuable input to the process of continuous improvement, and will serve as a basis for future nephrological research of excellence. No conflict of interestCopyright © 2023

Toxic epidermal necrolysis as a result of chlorthalidone and cyclophosphamide combination

Case report Introduction: Toxic epidermal necrolysis (TEN), is an immune-mediated disease characterized by severe mucocutaneous symptoms and is the result of an inflammatory response that leads to keratinocyte necrosis and perivascular lymphocyte infiltration, mostly drug-related. Case report: A 35-year- old male, with a history of recently diagnosed systemic lupus under treatment with prednisone, hydroxychloroquine, mycophenolate and cotrimoxazole forte evolves with persistent proteinuria, it is decided to add losartan, chlorthalidone and atorvastatin. Nevertheless despite immunosuppression, proteinuria and skin involvement persisted, so mycophenolate was suspended and a bolus of cyclophosphamide 1 g was administered. Eight weeks after adjusting treatment, the patient went to the emergency department due to a confluent, pruritic, maculopapular rash with blistering lesions on the trunk, upper limbs, face, and oral mucosa, associated with fever over 38degreeC, that evolved during one week. On admission, the following was confirmed: confluent erythematous macular exanthem associated with multiple flaccid blisters on the chest, upper limbs and neck, Nikolsky's sign (+), keratoconjunctivitis and dryness on the lips. Admission tests included complete blood count with no leukocytosis or eosinophilia, ESR 29 mm/hr, C-RP 19.8 mg/L, no liver profile abnormalities, creatinine 0.8 mg/dl, and urine test with proteinuria 300 mg/dl. Negative infectious study for mycoplasma, herpes 6 virus, cytomegalovirus, Epstein barr virus, hepatitis A, B, C, E and SARS-COV2 virus. Due to severe mucosal skin involvement, TEN/SJS was suspected v/s (TEN)-like Lupus presentation, drugs used prior to admission (chlorthalidone, losartan, atorvastatin) were discontinued, and treatment was started with Hydrocortisone 100 mg every 8 hours IV, Immunoglobulin 2 g/kg daily IV for 4 days, plus skin and mucous membrane care. Patient had a favorable evolution, with resolution of skin and mucosal lesions and no signs of infection. Skin biopsy showed necrotic epidermis, necrotic basal keratinocytes, and sparse lymphocytic inflammatory infiltrate in the papillary dermis, consistent with erythema multiforme/toxic epidermal necrolysis. Conclusion(s): Extensive mucosal involvement is one of the cardinal signs of the presentation of SJS/ETN and given its severity, a high index of suspicion is important with the consequent suspension of suspected drugs and support management for a favorable evolution. In this case the suspected culprit drug was the combination of cyclophosphamide and chlorthalidone, due to reports of increased toxicity of cyclophosphamide in combination with diuretic drugs.

Renal Amyloid-Associated (AA) Amyloidosis in a Sickle Cell Patient: A Case Report and Literature Review.

Renal amyloid-associated (AA) amyloidosis is a rare occurrence in sickle cell disease (SCD). Very little literature is available on renal AA amyloidosis in sickle cell disease. Nephrotic range proteinuria is associated with higher mortality among patients with SCD. We present a case of a young reproductive-age African American woman who presented with massive nephrotic range proteinuria. Other more common causes of AA amyloidosis such as immunologic and infectious etiologies were ruled out by history, physical examination, radiologic investigation, and serology. Renal biopsy showed mesangial expansion with Congo red-positive material. Staining for immunoglobulins was negative. Electron microscopy showed nonbranching fibrils. These findings were consistent with AA amyloidosis. This case report adds to the rare findings of renal AA amyloidosis in sickle cell disease. The patient refused any intervention to decrease her Glomerular Filtration Rate (GFR) in the hopes of potentially reversing the disabling proteinuria. We report sickle cell disease presenting with nephrotic syndrome secondary to AA amyloid.

Risk of glomerular diseases, proteinuria and hematuria following mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines.

BACKGROUND: With accruing case reports on de novo or relapsing glomerular diseases (GD) following different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, we evaluated the risk of GD following BNT162b2 and CoronaVac vaccines. METHODS: A modified self-controlled case series analysis was conducted using anonymized, territory-wide SARS-CoV-2 vaccination records in Hong Kong. All Hong Kong residents aged 18 years or above with outcomes of interest were included. Outcomes of interest were GD, proteinuria or hematuria within 42 days following each dose of SARS-CoV-2 vaccines. Incidence per 100 000 doses of SARS-CoV-2 vaccines administered was calculated, and incidence rate ratios (IRRs) were estimated using conditional Poisson regression with seasonality adjustment. RESULTS: Between 23 February 2021 and 31 March 2022, 4062 patients had an incident diagnosis of GD, proteinuria or hematuria, with 2873 of them being vaccinated during the observation period. The incidences of the composite events 1-41 days after vaccination were 3.7 (95% CI 3.1-4.4) per 100 000 doses of BNT162b2 administered, and 6.5 (95% CI 5.7-7.5) per 100 000 doses CoronaVac administered. There was no significant increase in the risks of composite events following the first (BNT162b2: IRR = 0.76, 95% CI 0.56-1.03; CoronaVac: IRR = 0.92, 95% CI 0.72-1.19), second (BNT162b2: IRR = 0.92, 95% CI 0.72-1.17; CoronaVac: IRR = 0.88. 95% CI 0.68-1.14) or third (BNT162b2: IRR = 0.39. 95% CI 0.15-1.03; CoronaVac: IRR = 1.18. 95% CI 0.53-2.63) dose of SARS-CoV-2 vaccines. CONCLUSIONS: There was no evidence of increased risks of de novo or relapsing GD with either BNT162b2 or CoronaVac vaccines.

Changing Trends of Pregnancy Related Acute Kidney Injury - a Single Centre Prospective Observational Study from Southern India

Introduction: Pregnancy-related acute kidney injury (PR-AKI) in India is largely showing a declining trend due to improved and accessible obstetric care. Nevertheless, PR-AKI continues to cause significant maternal and fetal morbidity and mortality. This study was taken up with the intention to study the incidence and clinical spectrum of AKI in pregnancy in recent times and assess maternal and neonatal outcomes Methods: All pregnant women admitted in the Department of Obstetrics and Gynecology at St John's Medical College Hospital, Bengaluru between January 2018 to June 2020 were screened for AKI with the following criteria 1. Increase in serum creatinine to >0.8mg/dL and/or a sudden increase in serum creatinine by more than 50% when prior renal function was normal. 2. Oligo-anuria 3. Need for renal replacement therapy Women with preexisting CKD were excluded. Patient's clinical and laboratory details recorded. Dialysis support was provided if indicated. The clinical profile and renal outcome of the mother and fetal outcome was assessed at the time of discharge. Mothers' were also followed up at the end of 3 months of postpartum period. Recovery was categorized as Complete recovery- normal serum creatinine (<0.8 mg/dL) or a previously known baseline and no proteinuria /hypertension at the end of 3 months Partial recovery- renal function improved but serum creatinine did not return to normal range and patient was dialysis independent. No recovery- patient continued to require dialysis at the end of 3months. Result(s): Of the 2650 deliveries in the study period 42 women (Mean age 26.9 +/-3.6 years) were diagnosed AKI during pregnancy (1.58%). Baseline characteristics and outcomes are depicted in table 1. Majority of women (n=37) were referred from peripheral hospitals. Hypertension and decreased fetal movements were the common reasons for referral. Third trimester was the most common time of presentation (76.1%). Severe Preeclampsia and HELLP syndrome was the leading cause of AKI (59.5%).ATN secondary to obstetric complications, sepsis and hemolytic uremic syndrome were the other causes. One case each of cortical necrosis, acute fatty liver of pregnancy and COVID 19 associated AKI was seen. Mean duration of hospital stay was 12.1+/-6.9 days. More than one third patients' required ICU stay (35.7%).12 patients (28.5%) required renal replacement therapy. Of them, 3 were dialysis dependent at the end of 3 months and 4 had partial renal recovery. 3 patients expired during hospital stay. Fetal survival was 69.04%.13 babies' required NICU care (44.8%). Neonatal outcomes are summarized in table 2. Close to one third of the pregnancies with AKI were associated with intrauterine fetal demise (28.5%). Low birth weight and prematurity were the common reasons for NICU admission with mean NICU stay of 8.2 +/-2.3 days [Formula presented] [Formula presented] Conclusion(s): Severe preeclampsia was the most common cause of AKI in our study. PR-AKI continues to be a significant problem in the peripheries of developing countries where availability of health care facilities is meager, with late referral to tertiary care centers. One third of the patients required ICU stay & dialytic support. Women who required dialysis had poorer renal prognosis. There was 30% fetal loss seen in PR-AKI and also a higher incidence of low birth weight and prematurity. No conflict of interestCopyright © 2023

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

Impact of Covid Vaccination on Hospitalized Covid-19 Patients - a Renal and Extra-Renal Outcome Study

Introduction: Covid-19 vaccinations are effective as preventive measures against the COVID-19 pandemic infection. There are different types of COVID-19 vaccines available worldwide. The impacts of different types COVID-19 vaccination on hospitalized patients remained uncertain at the early stage of the outbreak. This study examines the clinical outcomes of vaccinated and vaccine naive hospitalized COVID-19 patients. Method(s): This is a retrospective study of hospitalized COVID-19 patients admitted into University Malaya Medical Center from January 2021 until June 2021. Data on patients who were>= 18 years old and hospitalized for >= 48 hours for confirmed COVID-19 infection were captured. Clinical parameters and demographic of patients were collected from electronic medical records (EMR). Vaccine status was determined based on EMR entry and retrospective phone interviews. 2 cohorts of patients were classified based on their COVID vaccination status, and outcome analysis was done with appropriate statistical methods. Result(s): A total of 1529 patients were captured with a male-to-female ratio of 759 (49.6%) and 770 (50.3%). The median age was 55 (IQR: 36-66). 182 patients (12%) received COVID-19 vaccination before admission. The types of COVID vaccination received by patients were Pfizer (n=127;8.4%), AstraZeneca (n=27;1.8%), and Sinovac (n=28;1.8%) respectively.107 patients (7.1%) received two doses of vaccine, 72 patients had one dose (4.7%), and three were injected with three doses (0.2%). Biochemical analysis showed that the vaccination naive group has a higher median of lymphocyte counts (17 vs. 2.02;p<0.001), ferritin (363 vs 221;p=0.001), serum creatinine (67 vs 63;p=0.032). Renal outcome data revealed that unvaccinated patients had more incidence of acute kidney injury (AKI) (92.9% vs 7.1%;p=0.002) and increased level proteinuria (88.5% vs 11.5%;p= 0.011). Covid-19 vaccination group had lower incidence rate of pneumonia (8.9% vs 91.1%;p<0.001), lower ventilator use (4.8% vs 95.2%;p=0.01), and lower ICU admission (5.1% vs 94.9%;p<0.001) compared to vaccine-naive group. The mortality rate was lower 5.2% (n=7) in COVID-19 vaccination compared to 94.8% (n=127) vaccine-naive group;p=0.012. [Formula presented] Conclusion(s): In our study, COVID-19 vaccination effectively lowered the incidence of AKI, pneumonia, ICU admission, and mortality translating to better overall outcome. No conflict of interestCopyright © 2023

COVID-19 and kidneys: A follow-up.

In coronavirus disease 2019 (COVID-19) patients, acute tubular injury is the most frequently documented kidney disease. According to the current knowledge, its cause is assumed to be multifactorial. Other kidney diseases observed in non-severely ill COVID-19 patients are thrombotic microangiopathy, necrotizing glomerulonephritis, primary podocytopathy and interstitial nephritis. Even after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, necrotizing glomerulonephritis and other kidney diseases were observed. It is recommended that a renal biopsy be performed in COVID-19 patients with elevated creatinine, proteinuria, and/or hematuria to rule out a variety of other renal disorders. Both diseases (during a SARS-CoV-2 infection and after vaccination) probably share common features that act as triggers when the patient is preconditioned for a renal disease. The activation of the complement system and the formation of neutrophil extracellular traps (NET) could play a role in the pathogenesis. As the first report on autopsies carried out on COVID-19 patients throughout Germany showed, the autopsy plays a central role for a better understanding of this (relatively) new disease.Copyright © 2022, The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.

A Case of Iga Vasculitis That Developed Gross Hematuria and Lower-Limb Purpura Following Covid-19 Vaccines

Introduction: There have been some reports on flare-ups of kidney diseases following COVID-19 vaccines such as IgA nephropathy and minimal change disease. However, there have been few reports on those of IgA vasculitis following the vaccines yet. We report a case of IgA vasculitis with a flare-up of gross hematuria and lower-limb purpura following Moderna COVID-19 vaccines. Method(s): The patient is a 16-year-old female with no previous history of abnormal results of urinalyses before April in 2021. She had developed microscopic hematuria, proteinuria and purpura on both of her lower limbs that emerged and then disappeared repeatedly since then. She received Moderna COVID-19 vaccines in August and September in 2021, both of which were followed by gross hematuria lasting for around 10 days. The lower-limb purpura reemerged at the same time as the hematuria. Microscopic hematuria of around 30-49 RBC/HPF, glomerular hematuria of moderate degree and urine protein-to-creatinine ratio (UPCR) of around 0.8 g/gCr had continuously been detected. Skin and kidney biopsies were performed in December in 2021 and in February in 2022 respectively. Result(s): The skin tissue showed formation of leukocytoclastic vasculitis, and the kidney tissue showed that of cellular and fibrocellular crescents and endocapillary hypercellularity. Immunofluorescence staining of both tissues showed deposition of galactose-deficient IgA1(Gd-IgA1) and C3, and she was diagnosed as IgA vasculitis. She received steroid pulse therapy followed by tonsillectomy. The lower-limb purpura has disappeared after she received three courses of the steroid pulse therapy, but microscopic hematuria and UPCR of around 0.8 g/gCr have still continued. Conclusion(s): IgA vasculitis is leukocytoclastic vasculitis characterized by deposition of Gd-IgA1 on microvessel walls in skin and on glomerular capillaries in kidneys. The detailed mechanism of IgA vasculitis has not been fully elucidated yet. Gross hematuria following an upper respiratory infection is considered as a characteristic clinical symptom of IgA vasculitis as well as IgA nephropathy. Post-vaccination gross hematuria of patients with IgA nephropathy has been reported, and it is believed that innate immunity is related to its mechanism. Moderna COVID-19 vaccines, which the patient received, are mRNA vaccines. We estimate that exposure to the mRNA vaccine triggered excess glomerular deposition of Gd-IgA1-containing immune complexes and subsequent gross hematuria by overactivation of innate immunity such as Toll-like receptors that detect RNA. This case suggests that such immune activation by a mRNA vaccine might be related not only to the mechanism of IgA nephropathy but also to that of IgA vasculitis. No conflict of interestCopyright © 2023

New Onset Renal Replacement Therapy Is a Predictor of Covid-19 Adverse Outcome in Patients with Advanced Chronic Kidney Disease Due to Type 2 Diabetes Mellitus

Introduction: The patients with diabetic kidney disease (DKD) due to type 2 diabetes mellitus (T2DM) are at a high risk of adverse outcomes of COVID-19. In some cases, rapidly progressive kidney injury requires urgent initiation of renal replacement therapy (RRT) - hemodialysis de novo (HD de novo). The objective of this study is to identify risks factors of adverse outcomes and predictive value of HD de novo in patients with DKD due to T2DM and COVID-19. Method(s): The patients with chronic kidney disease 4-5 stages (CKD 4-5) with laboratory-confirmed COVID-19 were included in the retrospective observational study. The observation period 04.01-10.30.2020. Data were collected from electronic medical database. The following independent variables were analyzed at hospital admission: age, gender, body mass index (BMI), general comorbidity (Charlson Index, CCI), the insulin demand (InsD), fasting blood glucose (FBG), glomerular filtration rate (GFR), Plasma creatinine (Pcr), serum albumin (SA), proteinuria, time from onset to admission, NEWS2-scale points, pulmonary involvement (Chest CT), Hb, WBC, lymphocytes, platelet count, LDH, CPR, ferritin, D-dimer, procalcitonin, Interleukin-6. The observation group was divided into subgroups: 1 - HD not required (HD n/r), 2 - HD de novo. Result(s): A total of 55 patients were included. Mediana age was 69 y (IQR 64;80), fe-males 59%. The overall mortality - 38.2%. In 18 patients (32.7%) HD de novo was initiated due to rapidly progressive renal failure. The results of comparative analyses of demographic, initial clinical and laboratory data are presented in Tables (*Mann-Whitney U-test;IQR, interquartile range;Me, mediana). [Formula presented] [Formula presented] The mortality in both subgroups was 21.6 % vs 72.2 % respectively (p <0,001). HD de novo was determined as an independent predictor of adverse outcome (OR 9.42;95% CI, 2.58-34.4, p = 0.001). The analysis showed that FBG >= 10 mmol/L at admission (OR, 3.38;95% CI, 1.04-10.98, p = 0.050), SA at admission <= 35 g/L (OR 3.41;95% CI, 1.00-11.55, p = 0.050), News2 >4 points (OR 5.60;95% CI, 1.67-19.47, p = 0.006), GFR <= 20 ml/min/1,73m2 at admission (OR 4.24;95%;CI 1.29-13.99, p = 0.020) were independent predictors of HD de novo. Cumulative survival in subgroup HD de novo was 10% (significantly less, than in patients HD n/r) (Fig.). [Formula presented] Conclusion(s): Approximately every third patient with advanced nondialysis DKD required new onset RRT.New onset RRT is an independent predictor of lethal outcome of COVID-19. High FBG, low SA, low GFR and high NEWS2 score at admission are the risk factors of HD initiation during hospitalization. No conflict of interestCopyright © 2023