CHARACTERISTICS OF PATIENTS WHO RECEIVED BIOLOGICAL TREATMENT AFTER KIDNEY TRANSPLANTATION AND THE INCIDENCE OF SERIOUS INFECTIONS: A MULTICENTER STUDY

BackgroundKidney transplant patients due to both primary kidney involvement of chronic/autoimmune inflammatory diseases and end-stage kidney disease related to amyloidosis are followed up in rheumatology clinics. Biological agents one of the treatment options in kidney transplant recipients with chronic/autoimmune inflammatory disease.ObjectivesHowever, there is insufficient data on the development of infection in kidney transplant recipients who received biological treatment. Herein, we aimed to determine the incidence of serious infections in patients with kidney transplant recipients who are received biological therapy.MethodsKidney transplant recipients who are received biological agents due to rheumatologic disease were included in the study. Patients' demographic features, transplantation data, biological treatment, development of infection and severity of infection were screened retrospectively. Infections that requiring hospitalization were defined as severe infections.ResultsA total of 31 patients were included in the study, 14 (45%) of whom were female and mean age was 41 ±9 years. Twenty-five patients (80%) of them were non-preemptive kidney transplant and mean duration of hemodialysis before the transplantation was 40 ±40 months. Twenty-three patients (74%) had end stage kidney failure due to FMF-amyloidosis(Figure-1-). Seventeen patients (54%) received anakinra, 11 patients (35%) received canakinumab and 3 patients (10%) received etanercept with other immunosuppressive treatment. Mean treatment duration of biological agents was 4.2±2.6 years. Two patients developed solid organ malignancy and one patient developed hematological malignancy after transplantation. Sixteen of the patients (52%) were hospitalized at least once due to infection and 4 patients (13%) died due to infection. The cause of decease in two patients was COVID-19.ConclusionRheumatic diseases are an important cause of end-stage renal disease and definitive treatment is kidney transplantation. Kidney transplant recipients due to rheumatological disease also use biological agents in the post-transplantation period. Kidney transplant recipients have higher risk for the development of infection since they receive immunosuppressive therapy and use of biologic agents may further increase the risk for development infection. Meyer et al reported that infection developed in 54 of 187 solid organ transplant recipients using biological agents.[1] Mean treatment duration of biological agents was 12 months in this study. The incidence of infection was 54% in our study. Mean treatment duration of biological agent was 4.2 year was considered main reason for higher incidence of infection in our study.Reference[1]Meyer F, Weil-Verhoeven D, Prati C, Wendling D, Verhoeven F. Safety of biologic treatments in solid organ transplant recipients: A systematic review. Semin Arthritis Rheum. 2021 Dec;51(6):1263-1273. doi: 10.1016/j.semarthrit.2021.08.013. Epub 2021 Aug 26. Erratum in: Semin Arthritis Rheum. 2022 Aug;55:152015. PMID: 34507811.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

IMPACT OF CHRONIC KIDNEY DISEASE IN PATIENTS WITH AS USING BIOLOGIC AGENTS

BackgroundAlthough renal involvement is an rare extra-articular involvement in patients with ankylosing spondylitis (AS), medications and accopamyning comorbidities may adversly affect renal functions [1].ObjectivesTo determine the frequency and impact of CKD in patients with AS using biologic disease modyfying anti-rheumatic drugs (bDMARDs).MethodsBetween 2005 and November 2021, 3207 patients diagnosed with AS according to the modified New York criteria were enrolled in the Hacettepe University biological database (HUR-BIO). The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guideline was used for the definition of CKD to evaluate the renal function of patients. Glomerular filtration rate (GFR) was calculated with the MDRD (modified Modification of Diet in Renal Disease) formula, taking into account the creatinine value, age and gender parameters of the patients [2]. CKD was detected in 39 (1,2%) patients. Age-sex matched 41 non-CKD AS patients were selected as the control group. Demographic and clinical characteristics and mortality rates of AS patients with and without CKD were compared.ResultsOf 39 AS-CKD patients, 25 (64.1%) had CKD before the initation of bDMARD and and 14 (35.8%) developed CKD during follow-up after treatment was started. Patients with AS-CKD had longer duration of symptoms and disease (Table 1). Comorbidities such as hypertension, coronary artery disease and amyloidosis were more prevalent in patients with AS-CKD. At a median follow-up of 2.48(0.1-20.1) years, mortality was observed in 11(28.2%) patients in the AS-CKD group, while no mortality was observed in the age-sex matched AS-nonCKD group (p<0.001, Figure 1). The mortality rate in patients with AS-CKD was 12.6 per 1000 patient-years, and 4 (10.2%) of deaths were during the COVID-19 pandemia.Figure 1.Table 1.AS-CKD group (n=39)AS-nonCKD group (n=41)PTotal AS patients, (n=3207)Age, mean(SD), years68.2 (12.0)58.8(12.6)-47.9±(11.2)Male, n(%)27 (69.2)27(65.9)-1716(53.5)53.1)Symptom duration, years median (min-max)20 (5-42)11(2-30)0.0110(1-44)Disease duration, years median (min-max)14,5(5-42)7(1-29)0.046(1-37)HLA-B27 positivity, n(%)13(33.3)12(29.2)0.5826/2014(41.0)Uveitis, n(%)6/354/360.2339/2946(11.5)Inflammatory bowel disease, n(%)4/353/360.4135/2946(4.58)Smoking, ever, n(%)22/34 (64.7)20/36(55.5)0.31781/2942(60.5)BMI (kg/m2), mean(SD)28 (6.08)28.2(5.01)0.828.1(5.5)Amiloidosis, n(%)14/36(38.9)1(2.4)<0.00133/2949(1.11)Comotbidities n(%)• Diabetes Mellitus,7/34(20.6)4/36(11.1)0.2199/2949(6.7)• Hypertension27/34(79.4)9/36(25)<0.001442/2949(14.9)• CAD8/21(38.1)1/25(4)0.005110/1882(5.8)• COPD5/21(23.8)0/240.004117/1774(6.59)CRP, med(min-max)1.6(0.4-12.4)1.77(0.1-23.6)0.81.07(0.1-45)• at the initiation of bDMARDs, at the last visit,0.7(0.16-14)0.55(0.1-7.5)0.30.5(0.1-14)ESR, med(min-max)• at the initiation of bDMARDs,48(12-140)30(2-96)0.119(1-140)• at the last visit, med(min-max)25(3-93)15(2-70)0.113(1-110)BASDAI, mean (SD)• At the initiation of bDMARDs4.5(±2.1) 5.46(±2.07) 0.5 5.7(±2.04) • At the last vizit3.94(±2.35)2.95(±2.33)0.093.69(±2.5)CAD: Coronary artery disease, COPD: Chronic Obstructive pulmonary disease, BMI: Body mass index, BASDAI: Bath AS Disease Activity IndexConclusionBoth comorbid disease burden and mortality seem to be increased in patients with AS-CKD. Increased mortality was more pronounced during the COVID-19 pandemia.References[1]Coşkun, B.N., et al., Anti-TNF treatment in ankylosing spondylitis patients with chronic kidney disease: Is it effective and safe? Eur J Rheumatol, 2022. 9(2): p. 68-74.[2]Stevens, P.E. and A. Levin, Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med, 2013. 158(11): p. 825-30.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Neuromuscular disease: 2021 update.

This review highlights ten important advances in the neuromuscular disease field that were first reported in 2020. The overarching topics include (i) advances in understanding of fundamental neuromuscular biology; (ii) new / emerging diseases; (iii) advances in understanding of disease etiology and pathogenesis; (iv) diagnostic advances; and (v) therapeutic advances. Within this broad framework, the individual disease entities that are discussed in more detail include neuromuscular complications of COVID-19, supervillin-deficient myopathy, 19p13.3-linked distal myopathy, vasculitic neuropathy due to eosinophilic granulomatosis with polyangiitis, spinal muscular atrophy, idiopathic inflammatory myopathies, and transthyretin neuropathy/myopathy. In addition, the review highlights several other advances (such as the revised view of the myofibrillar architecture, new insights into molecular and cellular mechanisms of muscle regeneration, and development of new electron microscopy tools) that will likely have a significant impact on the overall neuromuscular disease field going forward.

British Society for Rheumatology Annual Conference 2023 Abstracts

The proceedings contain 343 papers. The topics discussed include: implementation of a disease modifying anti-rheumatic drug blood monitoring software: 8 years of experience in a single center;effectiveness of colchicine among patients with COVID-19 infection: a randomized, open labelled, clinical trial;rheumatic autoimmune diseases following COVID-19 infection: an observational study in Iraqi Kurdistan region;COVID-19 in male elite Irish-based athletes at a national sports institute;the effects of a pain management program for patients with an inflammatory arthritis;a retrospective analysis of the effectiveness safety of platelet rich plasma injections in primary osteoarthritis in knee joint, in patients attending a tertiary care hospital, Sri Lanka;a cohort study;do proformas used in fracture liaison service appointments reflect national osteoporosis clinical standards? a content analysis;calcium pyrophosphate dihydrate crystal in operated rheumatoid arthritis of the knee;cardiac amyloidosis: a case series of 31 patients with a comprehensive literature review;scoping review for the application of center of pressure for patient or intervention assessment in rheumatoid conditions;and four SNPs associated with monocyte/macrophage cell lineage uniquely associated with CRPS-1 in discovery and replication cohorts and suggest predisposition to regional osteopenia and digit misperception.

IgM Multiple Myeloma Presenting With Diarrhea

Introduction: IgM Multiple Myeloma (MM) is a rare subtype of MM consisting of <1% cases of MM. It is distinguished from Waldenstrom Macroglobinemia, which also produces IgM, by the absence of somatic mutation MYD88. We present a patient with a chief complaint of diarrhea which unknowingly led to his hematological diagnosis Case Description/Methods: A 64 year old male with RA-SLE overlap syndrome on steroids, and recent COVID19 pneumonia, had presented with 5 episodes of watery diarrhea every day and 40 Ib weight loss within 2 months. CT revealed small bowel enteritis and stool studies, including C. diff, cultures, ova and parasites were negative. Diarrhea persisted despite antibiotics, therefore an EGD and Colonoscopy were performed which showed duodenal lymphangiectasia and a normal colon. Duodenal biopsy revealed eosinophilic deposits in the villous lamina propria which stained for IgM and stained negative under congo red ruling out amyloidosis. SPEP and a bone marrow biopsy revealed monoclonal IgMspikes and plasma cells in the bone marrow suggesting MMalong with a co-existing population of CLL. Next-generation sequencing was negative forMYD88, supporting IgM MM instead of Waldenstrom. He developed a protein-losing enteropathy with dramatic hypoalbuminemia (albumin 0.9) and lower extremity edema and DVTs. He was started on chemotherapy and frequent albumin infusions. His diarrhea completely resolved, however not in time, as his other medical comorbidities lagged behind and he developed anasarca and continued to deteriorate. Discussion(s): Plasma cell dyscrasias such as IgM MM or more commonly Waldenstrom have rarely been reported to cause GI symptoms. GI involvement can include direct GI infiltration of plasma cells, IgM deposition, or the finding of a plasmacytoma. It has been speculated that IgM deposits can lead to interstitial viscosity and obstructive lymphangiectasia leading to diarrhea and a protein-losing enteropathy as in our patient. Protein loss has led him to have hypoalbuminemia and possibly loss of antithrombotic proteins that have caused DVTs. Few case reports have suggested that treating the underlying cause with chemotherapy stops diarrhea entirely. Although our patient's diarrhea ceased, we believe that it was not in time for him to entirely recover from the later complications of the disease. We hope that this case can help clinicians to attempt prompt treatment of patients when they find GI specimens showing IgM deposits and they suspect a plasma cell dyscrasia.

Improving cardiovascular outcomes for patients with heart failure in sub-Saharan Africa: conference proceedings of the 2022 Nigerian Cardiovascular Symposium.

The Nigerian Cardiovascular Symposium is an annual conference held in partnership with cardiologists in Nigeria and the diaspora to provide updates in cardiovascular medicine and cardiothoracic surgery with the aim of optimising cardiovascular care for the Nigerian population. This virtual conference (due to the COVID-19 pandemic) has created an opportunity for effective capacity building of the Nigerian cardiology workforce. The objective of the conference was for experts to provide updates on current trends, clinical trials and innovations in heart failure, selected cardiomyopathies such as hypertrophic cardiomyopathy and cardiac amyloidosis, pulmonary hypertension, cardiogenic shock, left ventricular assist devices and heart transplantation. Furthermore, the conference aimed to equip the Nigerian cardiovascular workforce with skills and knowledge to optimise the delivery of effective cardiovascular care, with the hope of curbing 'medical tourism' and the current 'brain drain' in Nigeria. Challenges to optimal cardiovascular care in Nigeria include workforce shortage, limited capacity of intensive care units, and availability of medications. This partnership represents a key first step in addressing these challenges. Future action items include enhanced collaboration between cardiologists in Nigeria and the diaspora, advancing participation and enrollment of African patients in global heart failure clinical trials, and the urgent need to develop heart failure clinical practice guidelines for Nigerian patients.

Multimodality imaging-based diagnosis of cardiac transthyretin amyloidosis

Introduction: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is a rare, progressive, life-threatening, hereditary disorder induced by a misfolded precursor protein, caused by mutations in the transthyretin gene. ATTR-CM is a challenging disease to recognize in early stages owing to its multisystem and nonspecific manifestations1-3. Case report: 65-year-old patient was hospitalized for the second time to our Clinic for Cardiovascular diseases in April 2022. Previous hospitalization happened 5 years ago and there was no ambulatory cardiology check-up between hospitalizations. He had progressive dyspnea on mild exertion and lower extremity edema. Therapy at home was furosemide occasionally. In past medical history he had left carpal tunnel surgery and Covid 19 infection in April 2022. On arrival blood pressure was 140/80 mmHg, pulse 100 beats per minute, absolutely arrhythmic. Basal weakened breath sounds, and leg edema were present. Troponin and NT pro BNP were elevated (91 ng/l and 3222 ng/l). 12-lead electrocardiogram showed peripheral micro-voltage, atrial fibrillation with ventricular rate around 110 bpm. Biatrial enlargement, increased left and right wall thickness, thickened papillary muscles, mildly reduced left ventricular ejection fraction and mono-phasic transmittal flow was found on transthoracic echocardiography. Testing for Fabry disease was negative. Cardiac magnetic resonance (CMR) found morphological changes and the pattern of contrast accumulation that suggested cardiac amyloidosis. Immunofixation electrophoresis showed no monoclonal (M) spike, gammopathy was unlikely. A biopsy of the buccal mucosa was performed, no amyloid deposits were found. Bone scintigraphy found accumulation of labelled hydroxydiphosphonate (HDP) that was visible in the myocardium, which points to ATTR-CM. Genetic testing is in progress. Conclusion: ATTR-CM requires a high index of suspicion, and it should be suspected in patients with LV hypertrophy and heart failure. The diagnosis of cardiac amyloidosis requires a combination of multi- modality imaging including echocardiography, CMR and scintigraphy. An imaging modality that can accurately diagnose ATTR-CM without the need for invasive cardiac biopsy is nuclear scintigraphy using bone-avid radio-tracers4. Timely diagnosis is important since the treatment is possible and improves prognosis in these patients. [ FROM AUTHOR] Copyright of Cardiologia Croatica is the property of Croatian Cardiac Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Echocardiographic phenotype in severe aortic valve stenosis with and without cardiac amyloidosis: The AMY-TAVI trial

Background: Longitudinal Strain (LS) pattern in cardiac amyloidosis (CA) typically spares the apex of the heart, which is a sensitive and specific finding that can be used to distinguish CA from other causes of left ventricular (LV) hypertrophy. RELAPS >1 suggests with high specificity CA, and shows a bright red in the apical segments of the polar map. Purpose(s): To identify differential echocardiographic characteristics of aortic stenosis (AS) with concomitant TTR-CA (AS-CA) compared to AS alone. Method(s): Patients with severe symptomatic AS undergoing TAVI were prospectively and consecutively included between Jan-19 and Dec-20. Pre-procedure, a complete echocardiogram was performed that included deformation parameters using Speckle-Tracking. Strain derived Indices accepted for CA screening were calculated: RELAPS: Relative apical LS (average apical LS/average basal+mid LS);SAB: (apical-septal/basal-septal LS);EFSR: (LVEF/GLS). After TAVI, a 99Tc-DPD scintigraphy and a proteinogram were performed to screen for CA. Result(s): 324 patients were included. The mean age was 81 yo, 52% women. 39 (12%) patients presented cardiac uptake on scintigraphy: 14 (4.3%) grade 1;13 (4%) grade 2, and 11 (3.4%) grade 3. Strain analysis could be performed in 243 patients due to acoustic window and covid19 pandemic restrictions. Echocardiographic characteristics between AS alone and those with grade 1 (AS-DTD1) and grade 2/3 (AS-CA) are shown in Table 1. Compared with AS alone, patients with AS-CA had significantly lower transvalvular gradients, although similar AVA, and low flow-low gradient (LF-LG) AS was more prevalent. AS-CA exhibited slightly worse cardiac remodeling (LV mass ind: 202 g/m2 vs 176 g/m2, p=0.032), and worse diastolic dysfunction, but without significant differences in thickness, diameters or volumes, with similar relative wall thickness (RWT: 0.53 vs. 0.51 mm, p=0.52). LVEF was similar, however myocardial contraction fraction (MCF= stroke volume/myocardial volume) and MAPSE were worse in AS-CA. GLS, RELAPS, SAB and EFSR were not different, but RELAPS >1 pattern was more prevalent in AS-CA (74% vs 44%, p=0,006) (Figure 1). Mass/strain ratio (RMS) was similar. There were no differences in size and fractional emptying of left atrium, or atrial septum thickness. Right ventricle (RV) size was similar, as well as conventional function parameters (TAPSE and S'). However, RV LS was worse in AS-CA. Pericardial effusion was more prevalent in AS-CA (25% vs 7.4%, p=0.013). In the multivariate analysis, predictors of AS-CA were: Age (OR: 1,2, p=0,02), BG (OR: 0,2, p=0,01), E/A (OR: 4,7, p=0,02), LV Mass index (OR: 1,02, p=0,04) and RELAPS >1 (OR: 0,12, p=0,01). Conclusion(s): Dual pathology of AS-AC is common in older patients referred for TAVI. Although it is more prevalent in patients with AS-CA, RELAPS>1 pattern can be present in almost 50% of patients with severe AS alone, which reduces its value as screening tool for CA in this clinical setting respect to others. (Table Presented).

Echocardiographic phenotype and prognostic value of relative apical sparing of longitudinal strain pattern in severe aortic stenosis with and without cardiac amyloidosis. The AMYTAVI study

Introduction: It is estimated that 15% of patients with AS have concomitant cardiac amyloidosis (CA). Left ventricular (LV) longitudinal strain (LS) pattern with relative apical sparing (RELAPS>1), shown as bright red in the apical segments on the polar map, has been strongly associated with CA. Its presence and its significance in AS is yet to be determined. Purpose(s): To determine the prevalence of the RELAPS>1 pattern in patients with severe AS with and without concomitant CA, and to analyze the echocardiographic phenotype associated with this strain pattern and its prognostic value. Method(s): Patients with severe symptomatic AS undergoing TAVI were prospectively and consecutively included between Jan-19 and Dec-20. Pre-procedure, a complete echocardiogram was performed that included deformation parameters using Speckle-Tracking. Strain derived Indices accepted for CA screening were calculated: RELAPS: Relative apical LS (average apical LS/average basal+mid LS);SAB: (apical-septal/basal-septal LS);EFSR: (LVEF/GLS). After TAVI, a 99Tc-PYP scintigraphy and a proteinogram were performed to screen for CA. Result(s): 324 patients were included. The mean age was 81 yo, 52% women. Strain analysis could be performed in 243 patients due to acoustic window and covid19 pandemic restrictions. Among those, 111 (46%) presented relative apical sparing (RELAPS>1). There were no differences in clinical characteristics between patients with RELAPS <1 and >1: Similar age, sex, cardiovascular risk factors and funcional class, renal function or NT-proBNP. Among patients with RELAPS>1 there was more frecuently CA with uptake grade 2 and 3 on scintigraphy (15% vs. 4.5%, P=0.006) (Figure 1). RELAPS>1 group showed greater LV hypertrophic remodeling: Thicker myocardial wall with smaller ventricular cavity, especially concentric hypertrophy;LVEF and GLS was similar, however, MAPSE and myocardial contraction fraction (MCF) were worse in RELAPS >1 group, and EFSR was significantly higher (4.2 vs 3.9, p=0.002). RELAPS >1 group had smaller aortic valve area (AVA: 0.6 vs 0.7 cm2, p=0.045), but similar transvalvular gradients due to lower stroke volume. It had larger atria and less left atrial (LA) fractional emptying, as well as higher prevalence of atrial fibrillation (AF: 41% vs 27%, p=0.03). Right ventricle (RV) size were similar, however, RV function was worse in RELAPS >1 group (TAPSE: 19 vs 21 mm, p=0.003;free Wall LS: -24 vs -27%, p=0.008). There was no difference in all-cause mortality at 1 year of follow-up between groups (6.4% vs. 6.3%, p=1). Figure 2 represents the morphological characteristics according to the LS phenotype. Conclusion(s): In severe AS, RELAPS >1 is present in almost half of the patients. It is associated with worse cardiac remodeling, as well as higher prevalence of AF. However, it wasn't associated with higher mortality at 1 year. 1 in 7 patients with AS and RELAPS >1 have concomitant ATTR CA grade 2/3.

Dilated Cardiomyopathy: Unmasking Contributing Etiologies

Background: The role of genetic conditions in the development of cardiomyopathy is well established;however, recognition and referral for genetic testing remains underutilized. Systematic review of complex cases can increase general awareness in this area of practice. Here we describe the case of a patient with resolved severe stress induced cardiomyopathy (SIC), who was ultimately found to have heterozygous transthyretin-mediated amyloidosis (TTRA). Case: A 27-year-old man (family history positive for a brother status post heart transplant) presented with ataxia and cough due to legionella pneumonia. TTE showed left ventricular (LV) diastolic diameter of 6.2cm, LV ejection fraction 20-25%. He suffered rapid decompensation with mixed cardiogenic/septic shock requiring peripheral VA ECMO and Impella-CP placement. Course notable for brief cardiac arrest on hospital day (HD) 2, incidental diagnosis of COVID 19 on HD 14, conversion to VV ECMO on HD 15, and ECMO decannulation on HD 23. Repeat TTE prior to discharge showed normalization of biventricular function. Discussion(s): Despite resolution of refractory shock and normalization of biventricular function prior to discharge, the TTE finding of mild LV dilation and strong family history prompted outpatient pursuit of genetic testing which revealed a heterozygous TTRA mutation (val142ile). Work-up to assess cardiac involvement included: a 99m-technetium pyrophosphate scintigraphy found to be indeterminate, an aborted endomyocardial biopsy due to inability to smoothly advance a bioptome (presumably related to ECMO cannulation), and a cardiac MRI (pending at the time of this submission). If a cardiac phenotype is discovered, the patient will be started on targeted treatment of cardiac amyloid. Screening of first-degree family members has been initiated. Conclusion(s): Given the current state of under-diagnosis of genetic cardiomyopathies and its association with significant morbidity and mortality, it is prudent to consider genetic testing in young patients based on clinical history. Examples of clinical scenarios to prompt further testing include: anatomical findings (i.e. cardiac chamber enlargement, left ventricular hypertrophy), family history of cardiomyopathy, or clinical markers suggestive of alternative diagnoses (i.e. neuropathy, renal insufficiency, mediastinal lymphadenopathy). This thoughtful and algorithmic use of genetic testing may help improve long-term patient outcomes given improvements in both detection, family screening, and treatment for disease-specific cardiomyopathies.Copyright © 2022

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

Post COVID-19 AA amyloidosis of the kidneys with rapidly progressive renal failure.

Coronavirus disease 2019 (COVID-19) pandemic has taken the world by a storm, posing a gruelling challenge to the medical fraternity globally. Besides its very high infectivityinfectivity, significant organ dysfunction occurs in critically ill COVID-19 patients, leading to severe morbidity and mortality. Pulmonary involvement is the leading cause of death in these patients to be followed by the cardiovascular involvement. Kidney involvement due to COVID-19 is becoming more discernible with AKI adversely affecting the outcome. Besides AKI, a few cases of collapsing FSGS in genetically vulnerable patients and thrombotic microangiopathies have been reported as well. We report a case of AA amyloidosis of the kidney with a rapidly progressive renal failure and congestive heart failure with preserved left ventricular functions, which complicated a moderate COVID-19 pneumonia providing some clues to a possible association of this novel virus disease with this complication, which needs to be confirmed in future studies.

Controversial Properties of Amyloidogenic Proteins and Peptides: New Data in the COVID Era.

For a long time, studies of amyloidogenic proteins and peptides (amyloidogenic PPs) have been focused basically on their harmful properties and association with diseases. A vast amount of research has investigated the structure of pathogenic amyloids forming fibrous deposits within or around cells and the mechanisms of their detrimental actions. Much less has been known about the physiologic functions and beneficial properties of amyloidogenic PPs. At the same time, amyloidogenic PPs have various useful properties. For example, they may render neurons resistant to viral infection and propagation and stimulate autophagy. We discuss here some of amyloidogenic PPs' detrimental and beneficial properties using as examples beta-amyloid (ß-amyloid), implicated in the pathogenesis of Alzheimer's disease (AD), and α-synuclein-one of the hallmarks of Parkinson's disease (PD). Recently amyloidogenic PPs' antiviral and antimicrobial properties have attracted attention because of the COVID-19 pandemic and the growing threat of other viral and bacterial-induced diseases. Importantly, several COVID-19 viral proteins, e.g., spike, nucleocapsid, and envelope proteins, may become amyloidogenic after infection and combine their harmful action with the effect of endogenous APPs. A central area of current investigations is the study of the structural properties of amyloidogenic PPs, defining their beneficial and harmful properties, and identifying triggers that transform physiologically important amyloidogenic PPs into vicious substances. These directions are of paramount importance during the current SARS-CoV-2 global health crisis.

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.

Amyloidogenesis: What Do We Know So Far?

The study of protein aggregation, and amyloidosis in particular, has gained considerable interest in recent times. Several neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's (PD) show a characteristic buildup of proteinaceous aggregates in several organs, especially the brain. Despite the enormous upsurge in research articles in this arena, it would not be incorrect to say that we still lack a crystal-clear idea surrounding these notorious aggregates. In this review, we attempt to present a holistic picture on protein aggregation and amyloids in particular. Using a chronological order of discoveries, we present the case of amyloids right from the onset of their discovery, various biophysical techniques, including analysis of the structure, the mechanisms and kinetics of the formation of amyloids. We have discussed important questions on whether aggregation and amyloidosis are restricted to a subset of specific proteins or more broadly influenced by the biophysiochemical and cellular environment. The therapeutic strategies and the significant failure rate of drugs in clinical trials pertaining to these neurodegenerative diseases have been also discussed at length. At a time when the COVID-19 pandemic has hit the globe hard, the review also discusses the plausibility of the far-reaching consequences posed by the virus, such as triggering early onset of amyloidosis. Finally, the application(s) of amyloids as useful biomaterials has also been discussed briefly in this review.

Long-term use of colchicine: "The time to guard against chronic toxicity among patients of familial Mediterranean fever”

Colchicine is a cheap easily available and accessible drug that has been tried in different diseases which are not limited to gout, familial Mediterranean fever (FMF), Behcet's disease, and constipation, and has recently been tried for the treatment of COVID-19 and heart diseases. There are many emerging reports of toxicity related to colchicine use. Patients with FMF are using this drug lifelong. We are sounding the alarm for monitoring patients with FMF to guard against chronic colchicine toxicity.

A case of cerebral amyloid angiopathy related inflammation after vaccination against SARS-CoV-2

Background: Cerebral amyloid angiopathy related inflammation (CAA-RI) is a neuroinflammatory disease that is associated with perivascular amyloid- deposition. Case presentation: A middle-aged woman with a remote history of autoimmune disorders presented with unilateral migraine headaches, dizziness, unsteadiness, and fogginess 36 hours after administration of mRNA vaccine against SARS-CoV-2. Initially, unilateral leptomeningeal enhancement on MRI on the same side of headaches raised suspicion for leptomeningeal involvement of her known cutaneous T-cell lymphoma in remission. After two relatively unremarkable CSF analyses, she underwent a brain biopsy which showed amyloid deposits in vessels instead of lymphomatous infiltration. She was diagnosed with CAA-RI, and the headache and cognitive symptoms responded well to high-dose corticosteroids with a slow taper. Discussion/conclusion: We review the clinical literature of CAA-RI and its potential association with amyloid-related imaging abnormalities (ARIA) after administration of immunotherapy against amyloid.Copyright © 2022

Clinical case of SARS-CoV-2 infection in a patient with rheumatoid arthritis and secondary AA-amyloidosis of the lungs

In rheumatic diseases, the risk of infections development is higher than in the general population. The article describes a case of SARS-CoV-2 infection in a patient with rheumatoid arthritis (RA) and secondary AA-amyloidosis of the lungs, which led to a fatal outcome. In the context of the COVID-19 pandemic, RA patients with secondary AA-amyloidosis and pulmonary fibrosis are likely to represent a special risk group for developing a severe course of this infection with a fatal outcome. © 2023, Ima-Press Publishing House. All rights reserved.

Effusive Constrictive Pericarditis in the Setting of Recurrent Covid-19 Infection in a Vaccinated Patient

Background Effusive constrictive pericarditis is one of the rare reported complications of COVID-19 infection. Case 58-yr-old female with history of COVID pneumonia 7 months ago presented with shortness of breath, cough and dizziness. She was tachycardic with soft BP. Transthoracic echocardiography was suggestive of effusive constrictive pericarditis and moderate pericardial effusion. COVID-19 test came back positive. She previously received 2 doses of COVID-19 vaccine. Decision-making Cardiac MRI showed thickened pericardium, multiple complex loculated pericardial fluid with septations and focal areas of pericardial hyper-enhancement suggestive of inflammation and fibrosis. There was no clear cause of constrictive pericarditis other than recurrent COVID-19 infection. Pericardial biopsy was negative for malignancy. Nuclear study was negative for cardiac amyloidosis. connective tissue disease markers were negative. The patient was planned to do right heart catheterization, however given her COVID infection, the decision was to hold on non-urgent interventions. Her infection was managed aggressively. Final plan was pericardiectomy after resolution of infection with urgent intervention in case of any hemodynamic instability. Conclusion Effusive constrictive pericarditis requiring pericardiectomy is a rare finding in patients with recurrent COVID 19 infection especially after vaccination. Early diagnosis and treatment is very important to prevent significant morbidity. [Formula presented]Copyright © 2023 American College of Cardiology Foundation

A case of severe increase of liver enzymes in a ATTRv patient after one year of inotersen treatment.

BACKGROUND: Inotersen is an antisense oligonucleotide used to treat hereditary transthyretin amyloidosis (ATTRv). The most common drug-related adverse effects (AEs) include thrombocytopenia and glomerulonephritis. Hepatic damage is rare, but liver enzyme monitoring is mandatory. CASE REPORT: A 70-year-old man with ATTRv (Val30Met) treated with inotersen developed a severe increase of transaminases, with normal bilirubin and cholinesterase levels, that forced us to stop therapy. At the same time, other causes of acquired hepatitis were excluded, and the hypothesis of an inotersen-related hepatic toxicity was supported by the normalization of liver enzymes after 40 days from the drug interruption. DISCUSSION: Our case showed that 1-year inotersen treatment can stabilize neurological impairment and even improve quality of life and suggests to carefully monitor liver enzymes in order to avoid an inotersen-related hepatic dysfunction.