Kidney Replacement Therapy in Brazil: A Retrospective Cohort Study Based on Analysis of the Brazilian Public Health System.

BACKGROUND: Brazil has the largest Public Health System providing universal coverage for chronic dialysis. The objective was to describe the number, sociodemographic, and clinical characteristics of patients undergoing kidney replacement therapy (KRT) by dialysis within the Public Health System in Brazil. METHODS: We carried out a retrospective cohort study analyzing the database from the Brazilian Public Health System, focusing on procedures related to KRT. The study encompassed both prevalent and incident patients who underwent KRT in Brazil between 2015 and 2023. RESULTS: We observed an increase in the number and prevalence rate of dialysis patients from 2015 to 2023. We also noticed an increase in the age at dialysis initiation and in the prevalence of mixed-race patients and a reduction in the proportion of those undergoing peritoneal dialysis and with arteriovenous fistula. We identified an upward trajectory in the values of single-pool Kt/V over the years, contrasting with a decline in hemoglobin levels. The overall estimated prevalence rate of dialysis patients increased from 654 per million population (pmp) to 792 pmp over the years. The survival rates of incident KRT patients at 12 and 96 months were 81% and 60%, respectively. CONCLUSION: We reported an increase in the age at which dialysis began and a decline in the adoption of peritoneal dialysis over the years. While there have been some improvements over the years resulting in better adequacy of hemodialysis as measured by Kt/V, controlling certain parameters such as hemoglobin levels has remained challenging.

Overlap of membranous nephropathy and IgA nephropathy in a patient with Kimura's disease: a case report and literature review.

Introduction: Kimura's disease (KD) is a rare chronic inflammatory disorder characterized by subcutaneous lymphoid hyperplasia with peripheral eosinophilia. Kidney involvement is reported in 15%-18% of adult patients with KD, in many cases as nephrotic syndrome. We present a case of overlapping membranous nephropathy and IgA nephropathy associated with KD. Case report: A 27-year-old man was admitted with a history of bilateral leg edema for the last 2 months and concomitant progressive increase of cervical mass and fever. Laboratory findings were as follows: peripheral leukocyte count, 10,080/mm³; eosinophils, 3,200/mm³ (31.7%); serum creatinine, 0.83 mg/dL; and eGFR: 140 mL/min per 1.73 m2. Urinalysis revealed the presence of hematuria and proteinuria and the following results: 24-h proteinuria, 12.9 g; serum albumin, 1.3 g/dL; and elevated IgE level, 750 kU/L. Serologies for hepatitis B, hepatitis C, HIV, and VDRL were all negative. Complement C3 and C4 levels were normal. No monoclonal protein was detected in blood and urine. Parasite infestation was discarded. A biopsy of the cervical lymph node revealed eosinophilic lymphoid hyperplasia, suggesting KD. A kidney biopsy revealed findings consistent with the overlapping of membranous nephropathy with IgA nephropathy. The patient was treated for KD with prednisone 1 mg/kg/d with progressive dose tapering and posterior association of methotrexate 15 mg/week. A renin-angiotensin system inhibitor was prescribed for nephrotic syndrome. The cervical mass regressed, and proteinuria achieved partial remission, with an increase in serum albumin level and normalization of eosinophils and IgE levels. Conclusion: Although uncommon, kidney involvement must be considered in patients with KD. Glomerular diseases are the most frequent form of kidney injury.

Podocytopathies associated with familial partial lipodystrophy due to LMNA variants: report of two cases.

Lipodystrophies are characterized by complete or selective loss of adipose tissue and can be acquired or inherited. Familial partial lipodystrophy (FPLD) is a hereditary lipodystrophy commonly caused by mutations in the LMNA gene. Herein, we report two cases of FPLD associated with podocytopathies. Patient 1 was diagnosed with FPLD associated with the heterozygous p.Arg482Trp variant in LMNA and had normal glucose tolerance and hyperinsulinemia. During follow-up, she developed nephroticrange proteinuria. Renal biopsy was consistent with minimal change disease. Patient 2 was diagnosed with FPLD associated with a de novo heterozygous p.Arg349Trp variant in LMNA. Microalbuminuria progressed to macroalbuminuria within 6 years and tonephrotic range proteinuria in the last year. He remained without diabetes and with hyperinsulinemia. Renal biopsy revealed focal segmental glomerulosclerosis not otherwise specified. This report provides further evidence of variable features of lipodystrophy associated with LMNA variants and the importance of long-term follow-up with evaluation of kidney dysfunction.

Impact of genetic background as a risk factor for atherosclerotic cardiovascular disease: A protocol for a nationwide genetic case-control (CV-GENES) study in Brazil.

Atherosclerotic Cardiovascular Disease (ASCVD) represents the leading cause of death worldwide, and individual screening should be based on behavioral, metabolic, and genetic profile derived from data collected in large population-based studies. Due to the polygenic nature of ASCVD, we aimed to assess the association of genomics with ASCVD risk and its impact on the occurrence of acute myocardial infarction, stroke, or peripheral artery thrombotic-ischemic events at population level. CardioVascular Genes (CV-GENES) is a nationwide, multicenter, 1:1 case-control study of 3,734 patients in Brazil. Inclusion criterion for cases is the first occurrence of one of the ASCVD events. Individuals without known ASCVD will be eligible as controls. A core lab will perform the genetic analyses through low-pass whole genome sequencing and whole exome sequencing. In order to estimate the independent association between genetic polymorphisms and ASCVD, a polygenic risk score (PRS) will be built through a hybrid approach including effect size of each Single Nucleotide Polymorphism (SNP), number of effect alleles observed, sample ploidy, total number of SNPs included in the PRS, and number of non-missing SNPs in the sample. In addition, the presence of pathogenic or likely pathogenic variants will be screened in 8 genes (ABCG5, ABCG8, APOB, APOE, LDLR, LDLRAP1, LIPA, PCSK9) associated with atherosclerosis. Multiple logistic regression will be applied to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI), and population attributable risks will be calculated. Clinical trial registration: This study is registered in clinicaltrials.gov (NCT05515653).

Tip Lesion Most Frequent FSGS Variant Related to COVID-19 Vaccine: Two Case Reports and Literature Review.

Large-scale COVID-19 vaccination has been one of the most effective strategies to control the spread of the SARS-CoV-2 virus. However, several cases of glomerular injury related to the COVID-19 vaccine have been described in the literature. We report two cases of a tip lesion variant of focal segmental glomerulosclerosis (FSGS), which presented with significant proteinuria and improved after immunosuppression. In our literature review, the tip lesion variant of FSGS is currently the most frequent variant associated with vaccination against COVID-19. Prognosis is favorable and without significant alterations in the tubulointerstitial or vascular compartments. Adverse effects of vaccines need to be recognized early and will help us to understand the immune and pathological mechanisms of kidney damage.

Idiopathic collapsing glomerulopathy is associated with APOL1 high-risk genotypes or Mendelian variants in most affected individuals in a highly admixed population.

Collapsing glomerulopathy (CG) is most often associated with fast progression to kidney failure with an incidence apparently higher in Brazil than in other countries. However, the reason for this occurrence is unknown. To better understand this, we performed an integrated analysis of clinical, histological, therapeutic, causative genetic and genetic ancestry data in a highly genetically admixed cohort of 70 children and adult patients with idiopathic CG (ICG). The disease onset occurred at 23 (interquartile range: 17-31) years and approximately half of patients progressed to chronic kidney disease requiring kidney replacement therapy (CKD-KRT) 36 months after diagnosis. Causative genetic bases, assessed by targeted-gene panel or whole-exome sequencing, were identified in 58.6% of patients. Among these cases, 80.5% harbored APOL1 high-risk genotypes (HRG) and 19.5% causative Mendelian variants (MV). Self-reported non-White patients more frequently had HRG. MV was an independent risk factor for progression to CKD-KRT by 36 months and the end of follow-up, while remission was an independent protective factor. All patients with HRG manifested CG at 9-44 years of age, whereas in those with APOL1 low-risk genotype, the disease arose throughout life. HRGs were associated with higher proportion of African genetic ancestry. Novel causative MVs were identified in COL4A5, COQ2 and PLCE1 and previously described causative MVs were identified in MYH9, TRPC6, COQ2, COL4A3 and TTC21B. Three patients displayed HRG combined with a variant of uncertain significance (ITGB4, LAMA5 or PTPRO). MVs were associated with worse kidney prognosis. Thus, our data reveal that the genetic status plays a major role in ICG pathogenesis, accounting for more than half of cases in a highly admixed Brazilian population.

Podocytopathies associated with familial partial lipodystrophy due to LMNA variants: report of two cases

SUMMARY Lipodystrophies are characterized by complete or selective loss of adipose tissue and can be acquired or inherited. Familial partial lipodystrophy (FPLD) is a hereditary lipodystrophy commonly caused by mutations in the LMNA gene. Herein, we report two cases of FPLD associated with podocytopathies. Patient 1 was diagnosed with FPLD associated with the heterozygous p.Arg482Trp variant in LMNA and had normal glucose tolerance and hyperinsulinemia. During follow-up, she developed nephrotic-range proteinuria. Renal biopsy was consistent with minimal change disease. Patient 2 was diagnosed with FPLD associated with a de novo heterozygous p.Arg349Trp variant in LMNA. Microalbuminuria progressed to macroalbuminuria within 6 years and to nephrotic range proteinuria in the last year. He remained without diabetes and with hyperinsulinemia. Renal biopsy revealed focal segmental glomerulosclerosis not otherwise specified. This report provides further evidence of variable features of lipodystrophy associated with LMNA variants and the importance of long-term follow-up with evaluation of kidney dysfunction.

Rivaroxaban to prevent major clinical outcomes in non-hospitalised patients with COVID-19: the CARE - COALITION VIII randomised clinical trial.

Background: COVID-19 progression is associated with an increased risk of arterial and venous thrombosis. Randomised trials have demonstrated that anticoagulants reduce the risk of thromboembolism in hospitalised patients with COVID-19, but a benefit of routine anticoagulation has not been demonstrated in the outpatient setting. Methods: We conducted a randomised, open-label, controlled, multicentre study, evaluating the use of rivaroxaban in mild or moderate COVID-19 patients. Adults ≥18 years old, with probable or confirmed SARS-CoV-2 infection, presenting within ≤7 days from symptom onset with no clear indication for hospitalization, plus at least 2 risk factors for complication, were randomised 1:1 either to rivaroxaban 10 mg OD for 14 days or to routine care. The primary efficacy endpoint was the composite of venous thromboembolic events, need of mechanical ventilation, acute myocardial infarction, stroke, acute limb ischemia, or death due to COVID-19 during the first 30 days. ClinicalTrials.gov: NCT04757857. Findings: Enrollment was prematurely stopped due to sustained reduction in new COVID-19 cases. From September 29th, 2020, through May 23rd, 2022, 660 patients were randomised (median age 61 [Q1-Q3 47-69], 55.7% women). There was no significant difference between rivaroxaban and control in the primary efficacy endpoint (4.3% [14/327] vs 5.8% [19/330], RR 0.74; 95% CI: 0.38-1.46). There was no major bleeding in the control group and 1 in the rivaroxaban group. Interpretation: On light of these findings no decision can be made about the utility of rivaroxaban to improve outcomes in outpatients with COVID-19. Metanalyses data provide no evidence of a benefit of anticoagulant prophylaxis in outpatients with COVID-19. These findings were the result of an underpowered study, therefore should be interpreted with caution. Funding: COALITION COVID-19 Brazil and Bayer S.A.

Rivaroxaban in Outpatients with Mild or Moderate COVID-19: Rationale and Design of the Study CARE (CARE - Coalition COVID-19 Brazil VIII). / Rivaroxabana em Pacientes Ambulatoriais com COVID-19 Leve ou Moderada: Fundamentação e Desenho do Estudo CARE (CARE ­ Coalition COVID-19 Brazil VIII).

BACKGROUND: Previous studies have demonstrated a high risk of arterial and venous thromboembolic events as a consequence of direct viral damage to endothelial cells by SARS-CoV-2 and a procoagulant milieu due to increased biomarkers, such as D-dimer, fibrinogen, and factor VIII. Although randomized controlled trials of antithrombotic therapies have been conducted in hospitalized patients, few have evaluated the role of thromboprophylaxis in an outpatient setting. OBJECTIVE: To assess whether antithrombotic prophylaxis with rivaroxaban reduces the risk of venous or arterial thrombotic events, invasive ventilatory support, and death in COVID-19 outpatients. METHODS: The COVID Antithrombotic Rivaroxaban Evaluation (CARE) study, a multicenter, randomized, open-label, controlled trial of rivaroxaban 10 mg once daily for 14 days or local standard treatment alone to prevent adverse outcomes, is registered in clinicaltrials.gov (NCT04757857). The inclusion criteria are adults with confirmed or suspected SARS-CoV-2 infection and mild or moderate symptoms without indication for hospitalization, within 7 days of symptom onset, and 1 risk factor for COVID-19 complication (> 65 years, hypertension, diabetes mellitus, asthma, chronic obstructive pulmonary disease or other chronic lung diseases, smoking, immunosuppression, or obesity). The primary composite endpoint, which includes venous thromboembolism, invasive mechanical ventilation, major acute cardiovascular events, and mortality within 30 days of randomization, will be assessed according to the intention-to-treat principle. All patients will provide informed consent. A significance level of 5% will be used for all statistical tests. RESULTS: Major thrombotic and bleeding outcomes, hospitalizations, and deaths will be centrally adjudicated by an independent clinical events committee blinded to the assigned treatment groups. CONCLUSION: The CARE study will provide relevant and contemporary information about the potential role of thromboprophylaxis in outpatients with COVID-19.

FUNDAMENTO: Estudos anteriores revelaram alto risco de eventos tromboembólicos arteriais e venosos como consequência de danos virais diretos do SARS-CoV-2 em células endoteliais e um meio procoagulante devido ao aumento de biomarcadores como o D-dímero, fibrinogênio, fator VIII. Foram realizados ensaios controlados randomizados de terapias antitrombóticas em pacientes internados, no entanto, poucos estudos avaliaram o papel da tromboprofilaxia no ambiente ambulatorial. OBJETIVO: Avaliar se a profilaxia antitrombótica com rivaroxabana reduz o risco de eventos trombóticos venosos ou arteriais, suporte ventilatório invasivo e morte em pacientes ambulatoriais com COVID-19. MÉTODOS: O estudo CARE é um ensaio randomizado, aberto, multicêntrico e controlado por rivaroxabana 10 mg uma vez por dia durante 14 dias ou tratamento local padrão isolado, para a prevenção de resultados adversos, registrado no Clinicaltrials.gov (NCT04757857). Os critérios de inclusão são adultos com infecção confirmada ou suspeita do SARS-CoV-2, com sintomas leves ou moderados, sem indicação de hospitalização, no prazo de 7 dias após o início dos sintomas e um fator de risco de complicação da COVID-19 (>65 anos, hipertensão, diabetes, asma, doença pulmonar obstrutiva crônica ou outras doenças pulmonares crônicas, tabagismo, imunossupressão ou obesidade). O desfecho primário composto inclui tromboembolismo venoso, necessidade de ventilação mecânica invasiva, eventos cardiovasculares agudos maiores e mortalidade no prazo de 30 dias após a randomização, sendo avaliado segundo o princípio da intenção de tratar. Todos os pacientes assinaram termo de consentimento. Foi estabelecido um nível de significância de 5% para todos os testes estatísticos. RESULTADOS: Os principais desfechos trombóticos e hemorrágicos, hospitalizações e mortes serão avaliados centralmente por um comitê de eventos clínicos independente, sob a condição cega para a alocação dos grupos de tratamento. CONCLUSÃO: O estudo CARE fornecerá informação relevante e contemporânea sobre o possível papel da tromboprofilaxia em pacientes ambulatoriais com COVID-19.

Primary Effusion Lymphoma: A Rare and Challenging Diagnosis for Recurrent Pleural Effusion.

Primary Effusion Lymphoma is an extremely rare and aggressive subtype of B-cell lymphoma, accounting for only <1% of all cases of this neoplasm. It has a unique clinical presentation because it has a predilection for appearing in body cavities, such as the pleural space, pericardium and peritoneum. It mainly affects immunocompromised individuals and may also affect individuals in the Mediterranean region and in areas endemic for human herpesvirus 8 (HHV-8). Herein, we report the case of an 83-year-old immunocompetent male complaining of coughing, fever and progressive dyspnea for 3 days. His past medical history revealed a recurrent pleural effusion for the last three years, as well as losing weight and malaise. A subsequent investigation revealed a PEL diagnosis of the pleura.

Five-year cardiovascular outcomes in patients with chronic myeloid leukemia treated with imatinib, dasatinib, or nilotinib: A cohort study using data from a large multinational collaborative network.

Background: Breakpoint cluster region-Abelson gene (BCR-ABL) tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, concern has arisen about the cardiac safety profile of these drugs. Objectives: This study aims to compare long-term risks of adverse cardiovascular and cerebrovascular events (ACE), heart failure or left ventricular ejection fraction (LVEF) < 50%, and venous thromboembolic events (VTE) in patients with CML treated with BCR-ABL TKIs, using data from a large multinational network. Methods: Patients aged ≥ 18 years with CML treated with imatinib, dasatinib, or nilotinib without prior cardiovascular or cerebrovascular disease were included. We used propensity score matching to balance the cohorts. The 5-year cumulative incidences and hazard ratios were calculated. Results: We identified 3,722 patients with CML under treatment with imatinib (n = 1,906), dasatinib (n = 1,269), and nilotinib (n = 547). Patients with imatinib compared to dasatinib showed a higher hazard ratio (HR) for ACE (HR 2,13, 95% CI 1.15-3.94, p = 0.016). Patients with imatinib presented a lower HR than nilotinib for ACE (HR 0.50, 95% CI 0.30-0.83, p = 0.0074). In relation to heart failure or LVEF < 50%, patients with imatinib had a higher HR than dasatinib (HR 9.41, 95% CI 1.22-72.17, p = 0.03), but no significant difference was observed between imatinib and nilotinib (HR 0.48, 95% CI 0.215-1.01, p = 0.064). Conclusion: In this retrospective study with a large number of patients with CML, those treated with nilotinib had a higher 5-year ratio of ACE, while patients with dasatinib showed a lower ratio than patients with imatinib. The ratio of heart failure was higher in patients with imatinib than in patients with dasatinib, but not when compared to nilotinib.

The relationship between chikungunya virus and the kidneys: A scoping review.

Several atypical forms of chikungunya fever (CHIK) have been described, including neurological, cardiac and renal involvement. These forms may be related to high morbidity and mortality rates. This scoping review based on the PubMed, Scopus, and WOS databases aims to identify and summarise all the available evidence regarding the clinical and histopathological presentations and risk factors associated with kidney injury related to CHIK, as well as the clinical impact. Thus, a total of 54 papers were selected from 1606 initial references after applying the defined inclusion criteria. Data on the association between kidney injury and CHIK are scarce, with studies only conducted in the acute phase of the disease, lacking further characterisation. Kidney injury incidence in hospitalised patients using the Kidney Disease Improving Global Outcomes criteria varies from 21% to 45%, being higher among patients with atypical and severe manifestations. Although acute kidney injury does not seem to be related to viraemia, it may be related to higher mortality. Few studies have described the renal histopathological changes in the acute phase of CHIK, with prevalent findings of acute interstitial nephritis with mononuclear infiltrate, glomerular congestion and nephrosclerosis. Only one study assessed the kidney function of patients in the subacute and chronic phases of CHIK. Additionally, individuals with comorbidities, including chronic kidney disease, may be among those with a greater risk of presenting worse outcomes when affected by CHIK. The results described herein may contribute to better understand the relationship between the kidneys and chikungunya virus.

Rivaroxabana em Pacientes Ambulatoriais com COVID-19 Leve ou Moderada: Fundamentação e Desenho do Estudo CARE (CARE - Coalition COVID-19 Brazil VIII) / Rivaroxaban in Outpatients with Mild or Moderate COVID-19: Rationale and Design of the Study CARE (CARE - Coalition COVID-19 Brazil VIII)

Resumo Fundamento Estudos anteriores revelaram alto risco de eventos tromboembólicos arteriais e venosos como consequência de danos virais diretos do SARS-CoV-2 em células endoteliais e um meio procoagulante devido ao aumento de biomarcadores como o D-dímero, fibrinogênio, fator VIII. Foram realizados ensaios controlados randomizados de terapias antitrombóticas em pacientes internados, no entanto, poucos estudos avaliaram o papel da tromboprofilaxia no ambiente ambulatorial. Objetivo Avaliar se a profilaxia antitrombótica com rivaroxabana reduz o risco de eventos trombóticos venosos ou arteriais, suporte ventilatório invasivo e morte em pacientes ambulatoriais com COVID-19. Métodos O estudo CARE é um ensaio randomizado, aberto, multicêntrico e controlado por rivaroxabana 10 mg uma vez por dia durante 14 dias ou tratamento local padrão isolado, para a prevenção de resultados adversos, registrado no Clinicaltrials.gov (NCT04757857). Os critérios de inclusão são adultos com infecção confirmada ou suspeita do SARS-CoV-2, com sintomas leves ou moderados, sem indicação de hospitalização, no prazo de 7 dias após o início dos sintomas e um fator de risco de complicação da COVID-19 (>65 anos, hipertensão, diabetes, asma, doença pulmonar obstrutiva crônica ou outras doenças pulmonares crônicas, tabagismo, imunossupressão ou obesidade). O desfecho primário composto inclui tromboembolismo venoso, necessidade de ventilação mecânica invasiva, eventos cardiovasculares agudos maiores e mortalidade no prazo de 30 dias após a randomização, sendo avaliado segundo o princípio da intenção de tratar. Todos os pacientes assinaram termo de consentimento. Foi estabelecido um nível de significância de 5% para todos os testes estatísticos. Resultados Os principais desfechos trombóticos e hemorrágicos, hospitalizações e mortes serão avaliados centralmente por um comitê de eventos clínicos independente, sob a condição cega para a alocação dos grupos de tratamento. Conclusão O estudo CARE fornecerá informação relevante e contemporânea sobre o possível papel da tromboprofilaxia em pacientes ambulatoriais com COVID-19.

Abstract Background Previous studies have demonstrated a high risk of arterial and venous thromboembolic events as a consequence of direct viral damage to endothelial cells by SARS-CoV-2 and a procoagulant milieu due to increased biomarkers, such as D-dimer, fibrinogen, and factor VIII. Although randomized controlled trials of antithrombotic therapies have been conducted in hospitalized patients, few have evaluated the role of thromboprophylaxis in an outpatient setting. Objective To assess whether antithrombotic prophylaxis with rivaroxaban reduces the risk of venous or arterial thrombotic events, invasive ventilatory support, and death in COVID-19 outpatients. Methods The COVID Antithrombotic Rivaroxaban Evaluation (CARE) study, a multicenter, randomized, open-label, controlled trial of rivaroxaban 10 mg once daily for 14 days or local standard treatment alone to prevent adverse outcomes, is registered in clinicaltrials.gov (NCT04757857). The inclusion criteria are adults with confirmed or suspected SARS-CoV-2 infection and mild or moderate symptoms without indication for hospitalization, within 7 days of symptom onset, and 1 risk factor for COVID-19 complication (> 65 years, hypertension, diabetes mellitus, asthma, chronic obstructive pulmonary disease or other chronic lung diseases, smoking, immunosuppression, or obesity). The primary composite endpoint, which includes venous thromboembolism, invasive mechanical ventilation, major acute cardiovascular events, and mortality within 30 days of randomization, will be assessed according to the intention-to-treat principle. All patients will provide informed consent. A significance level of 5% will be used for all statistical tests. Results Major thrombotic and bleeding outcomes, hospitalizations, and deaths will be centrally adjudicated by an independent clinical events committee blinded to the assigned treatment groups. Conclusion The CARE study will provide relevant and contemporary information about the potential role of thromboprophylaxis in outpatients with COVID-19.

ANCA-associated glomerulonephritis and lupus nephritis following COVID-19 vaccination: a case report and literature review.

With the coverage of COVID-19 vaccination, it has been possible to observe the potential side effects of SARS-CoV-2 vaccines, with the most common ones being fever, myalgia, headache, and fatigue. However, an association has been observed between new and recurrent kidney injuries, mainly glomerulonephritis and lupus nephritis associated with ANCA, with the Pfizer-BioNTech, Moderna, Sinovac, and AstraZeneca vaccines, although the relationship between them is not clear. We report a case of ANCA-related vasculitis and lupus glomerulonephritis after the second dose of the AstraZeneca vaccine. The elderly patient presented significant worsening of kidney function after immunosuppression and complications after a new onset COVID-19 infection that led to death. We provide a literature review about kidney damage related to ANCA vasculitis after COVID-19 vaccine, aiming for a better understanding of the pathophysiological mechanism of kidney injury, its presentation, and treatment.

Systemic amyloidosis journey from diagnosis to outcomes: a twelve-year real-world experience of a single center in a middle-income country.

BACKGROUND: Systemic amyloidosis is caused by the deposition of misfolded protein aggregates in tissues, leading to progressive organ dysfunction and death. Epidemiological studies originate predominantly from high-income countries, with few data from Latin America. Due to the non-specific clinical manifestations, diagnosing amyloidosis is often challenging and patients experience a long journey and delay in diagnosis. This study aimed to assess clinical and laboratory characteristics, the diagnostic journey, and outcomes of patients with biopsy-proven systemic amyloidosis diagnosed between 2009 and 2020 at a university referral center in a middle-income Latin American country. Patients´ medical records were retrospectively reviewed. RESULTS: One hundred and forty-three patients were included. The median age at diagnosis was 60 years and 54% were male. Until the diagnosis, most of the patients (52%) were seen by at least 3 specialists, the main ones being: general practitioners (57%), nephrologists (45%), and cardiologists (38%). The most common manifestations were renal (54%) and cardiac (41%) disorders, and cachexia was seen in 36% of patients. In 72% of the cases, ≥ 2 biopsies were required until the final diagnosis. The median time from symptoms onset to diagnosis was 10.9 months, and most patients (75%) had ≥ 2 organs involved. The following subtypes were identified: AL (68%), ATTR (13%), AA (8%), AFib (4%), and inconclusive (7%). Median OS was 74.3 months in the non-AL subgroup and 18.5 months in AL. Among AL patients, those with advanced cardiac stage had the worst outcome [median OS 8.6 months versus 52.3 for stage III versus I-II, respectively (p < 0.001)]. AL subtype, cardiac involvement, and ECOG ≥ 2 were identified as independent risk factors for reduced survival. CONCLUSIONS: Systemic amyloidosis is still an underdiagnosed condition and the delay in its recognition leads to poor outcomes. Medical education, better diagnostic tools, improvement in access to therapies, and establishment of referral centers may improve patient outcomes in middle-income countries.

Kidney injury associated with COVID-19 infection and vaccine: A narrative review.

The respiratory tract is the main infection site for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in many admissions to intensive care centers in several countries. However, in addition to lung involvement, kidney injury caused by the novel coronavirus has proven to be a significant factor related to high morbidity and mortality, alarming experts worldwide. The number of deaths has drastically reduced with the advent of large-scale immunization, highlighting the importance of vaccination as the best way to combat the pandemic. Despite the undeniable efficacy of the vaccine, the renal side effects associated with its use deserve to be highlighted, especially the emergence or reactivation of glomerulopathies mentioned in some case reports. This study aimed to identify the main renal morphological findings correlated with COVID-19 infection and its vaccination, seeking to understand the pathophysiological mechanisms, main clinical features, and outcomes.

Dialysis-related constrictive pericarditis: old enemies may sometimes come back / Pericardite Constritiva relacionada a diálise: velhos inimigos podem, às vezes, voltar

ABSTRACT Cardiovascular disease is the main cause of death in patients with chronic kidney disease (CKD). Several heart conditions have been associated with CKD, including myocardial and pericardial diseases. This paper describes a case of Dialysis-related constrictive pericarditis in a patient diagnosed with sudden hypotension during a hemodialysis session. A 65-year-old man diagnosed with hypertension, diabetes, obesity, and cirrhosis on hemodialysis for two years complained of symptoms during one of his sessions described as malaise, lipothymia, and confusion. The patient had a record of poor compliance with the prescribed diet and missed dialysis sessions. He was sluggish during the physical examination, and presented hypophonetic heart sounds, a blood pressure of 50/30mmHg, and a prolonged capillary refill time. The patient was referred to the intensive care unit and was started on antibiotics and vasoactive drugs. His workup did not show signs of infection, while electrocardiography showed low QRS-wave voltage. His echocardiogram showed signs consistent with a thickened pericardium without pericardial effusion. Cardiac catheterization showed equalization of diastolic pressures in all heart chambers indicative of constrictive pericarditis. The patient underwent a pericardiectomy. Examination of surgical specimens indicated he had marked fibrosis and areas of dystrophic calcification without evidence of infection, consistent with Dialysis-related constrictive pericarditis. Hypotension for unknown causes must be considered in the differential diagnosis of dialysis patients.

RESUMO A doença cardiovascular é a principal causa de morte em pacientes com doença renal crônica (DRC). Várias formas de acometimento cardíaco têm sido associadas. à DRC, incluindo doenças miocárdicas e pericárdicas. Este artigo descreve um caso de pericardite constritiva relacionada a em um paciente diagnosticado com hipotensão súbita durante uma sessão de hemodiálise. Um homem de 65 anos com diagnósticos prévios de hipertensão, diabetes, obesidade e cirrose em hemodiálise por dois anos queixou-se de sintomas durante uma de suas sessões, descritos como mal-estar, lipotímia e confusão mental. Apresentava histórico de baixa adesão à dieta prescrita e faltas frequentes às sessões de diálise. Ele estava fraco durante o exame físico e apresentava bulhas cardíacas hipofonéticas, pressão arterial de 50/30mmHg e tempo de enchimento capilar prolongado. O paciente foi encaminhado para a unidade de terapia intensiva e iniciou o tratamento com antibióticos e drogas vasoativas. Investigação laboratorial não mostrou sinais de infecção, enquanto o eletrocardiograma mostrou baixa voltagem de complexo QRS. Seu ecocardiograma evidenciou sinais consistentes com um pericárdio espessado, sem derrame pericárdico. O cateterismo cardíaco mostrou equalização das pressões diastólicas em todas as câmaras cardíacas, indicativo de pericardite constritiva. O paciente foi submetido a uma pericardiectomia. O exame anatomopatológico mostrou sinais de acentuada fibrose acentuada fibrose e áreas de calcificação distrófica sem evidência de infecção, consistente com pericardite constritiva relacionada a por diálise. A hipotensão por causas desconhecidas deve ser considerada no diagnóstico diferencial de pacientes em diálise.

Case report: Isolated tubular basement membrane deposits in a patient with systemic lupus erythematosus - A diagnostic challenge.

Lupus nephritis is one of the most serious and frequent manifestations of systemic lupus erythematosus. It usually presents in the first years of the disease, which suspicion should be raised in cases of elevated serum creatinine, presence of proteinuria above 500 mg/day or active urinary sediment, in the absence of other apparent causes such as urinary tract infection and use of nephrotoxic drugs. In most cases, it affects the glomerulus, and its presentation is rare in the form of isolated tubulo-interstitial disease. In this report, we describe a case of lupus nephritis diagnosed after 2 years of illness, in the form of atypical isolated tubular disease, characterized by massive deposits in the tubular basement membrane. Clinically, there were altered renal function, subnephrotic proteinuria, and evolution to a complete clinical response after immunosuppressive treatment.

Proposal for standardizing normal insulin ranges in Brazilian patients and a new classification of metabolic syndrome.

Background: Insulin resistance and/or hyperinsulinemia are closely linked to adiposity, metabolic syndrome (MetS) and prolonged inflammatory processes. Methods: We retrospectively analyzed 1,018 adult individuals with a mean age of 46 years (74% male) and classified them as: Metabolically normal: without any of the five criteria of the International Diabetes Federation (IDF) used for the diagnosis of MetS, plus normal fasting insulin (Men < 8 mU/L, Women < 10 mU/L); Level 1 MetS: with one or two IDF criteria, plus hyperinsulinemia (Men: ≥ 8 mU/L), and Women: ≥ 10 mU/L); Level 2 MetS: with three or more IDF criteria, plus hyperinsulinemia. Results: The mean values for fasting insulinemia in metabolically normal individuals was 4.6 ± 1.8 mU/L and 5.6 ± 2.3 mU/L, while their means for the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were 1.0 and 1.2 for men and women, respectively. In addition, the mean values for insulin (and HOMA-IR) for individuals with two normal anthropometric parameters (body mass index and waist girth), or two normal anthropometric parameters plus no IDF criteria, were similar to the metabolically normal group. Based on the obtained mean + 2 SD, we established the following insulin (and HOMA-IR) values as diagnostic cut-offs for hyperinsulinemia: Men: ≥ 8 mU/L (≥ 1.5), and Women: ≥ 10 mU/L (≥ 2.0). The mean serum insulin was significantly higher for individuals with Level 1 MetS (approx. 9 mU/L for both genders) compared with metabolically normal individuals, as was the prevalence of hepatic steatosis, which was more evident in men. Thus, the presence of one or two abnormal IDF criteria, combined with hyperinsulinemia and/or raised HOMA-IR, suggests the presence of MetS and insulin resistance. Patients of both genders with Level 2 MetS had higher serum insulin and/or HOMA-IR values than Level 1, as well as a higher prevalence of hypertension and hepatic steatosis, being more pronounced among men. The process was progressive and proportional to the degree of hyperinsulinemia. Conclusion: It is proposed that intervention against MetS progression should be started in individuals with Level 1 MetS, rather than waiting for more criteria for diagnostic confirmation, which this should help to reduce the occurrence of known complications such as type 2 diabetes, atherosclerosis, hypertension, and chronic kidney disease, among others.