A humanized IL-2 mutein expands Tregs and prolongs transplant survival in preclinical models.

Long-term organ transplant survival remains suboptimal, and life-long immunosuppression predisposes transplant recipients to an increased risk of infection, malignancy, and kidney toxicity. Promoting the regulatory arm of the immune system by expanding Tregs may allow immunosuppression minimization and improve long-term graft outcomes. While low-dose IL-2 treatment can expand Tregs, it has a short half-life and off-target expansion of NK and effector T cells, limiting its clinical applicability. Here, we designed a humanized mutein IL-2 with high Treg selectivity and a prolonged half-life due to the fusion of an Fc domain, which we termed mIL-2. We showed selective and sustainable Treg expansion by mIL-2 in 2 murine models of skin transplantation. This expansion led to donor-specific tolerance through robust increases in polyclonal and antigen-specific Tregs, along with enhanced Treg-suppressive function. We also showed that Treg expansion by mIL-2 could overcome the failure of calcineurin inhibitors or costimulation blockade to prolong the survival of major-mismatched skin grafts. Validating its translational potential, mIL-2 induced a selective and sustainable in vivo Treg expansion in cynomolgus monkeys and showed selectivity for human Tregs in vitro and in a humanized mouse model. This work demonstrated that mIL-2 can enhance immune regulation and promote long-term allograft survival, potentially minimizing immunosuppression.

Recurrence of membranous nephropathy after kidney transplantation: A multicenter retrospective cohort study.

Membranous nephropathy (MN) is a leading cause of kidney failure worldwide and frequently recurs after transplant. Available data originated from small retrospective cohort studies or registry analyses; therefore, uncertainties remain on risk factors for MN recurrence and response to therapy. Within the Post-Transplant Glomerular Disease Consortium, we conducted a retrospective multicenter cohort study examining the MN recurrence rate, risk factors, and response to treatment. This study screened 22,921 patients across 3 continents and included 194 patients who underwent a kidney transplant due to biopsy-proven MN. The cumulative incidence of MN recurrence was 31% at 10 years posttransplant. Patients with a faster progression toward end-stage kidney disease were at higher risk of developing recurrent MN (hazard ratio [HR], 0.55 per decade; 95% confidence interval [CI], 0.35-0.88). Moreover, elevated pretransplant levels of anti-phospholipase A2 receptor (PLA2R) antibodies were strongly associated with recurrence (HR, 18.58; 95% CI, 5.37-64.27). Patients receiving rituximab for MN recurrence had a higher likelihood of achieving remission than patients receiving renin-angiotensin-aldosterone system inhibition alone. In sum, MN recurs in one-third of patients posttransplant, and measurement of serum anti-PLA2R antibody levels shortly before transplant could aid in risk-stratifying patients for MN recurrence. Moreover, patients receiving rituximab had a higher rate of treatment response.

Urbanization and kidney dysfunction in Brazilian indigenous people: a burden for the youth.

OBJECTIVE: The aim of this study was to investigate whether the degree of urbanization influences the prevalence of chronic kidney disease in Brazilian indigenous people. METHODS: This is a cross-sectional study conducted between 2016 and 2017 in northeastern Brazil and includes individuals aged between 30 and 70 years from two specific indigenous groups who volunteered to participate in the study: the Fulni-ô people (lowest degree of urbanization) and the Truká group (greater degree of urbanization). Cultural and geographical parameters were used to characterize and measure the magnitude of urbanization. We excluded individuals with known cardiovascular disease or renal failure who required hemodialysis. Chronic kidney disease was defined as a single measurement of an estimated glomerular filtration rate <60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. RESULTS: A total of 184 indigenous people from the Fulni-ô group and 96 from the Truká group with a median age of 46 years (interquartile range: 15.2) were included. We found a chronic kidney disease rate of 4.3% in the total indigenous population, generally affecting an older population: 41.7% over 60 years old (p<0.001). The Truká people had a chronic kidney disease prevalence of 6.2%, with no differences in kidney dysfunction across age groups. The Fulni-ô participants had a chronic kidney disease prevalence of 3.3%, with a higher proportion of kidney dysfunction in older participants (of the six Fulni-ô indigenous people with chronic kidney disease, five were older). CONCLUSION: Our results suggest that a higher degree of urbanization seems to negatively influence the prevalence of chronic kidney disease in Brazilian indigenous people.

Urbanization and kidney dysfunction in Brazilian indigenous people: a burden for the youth

SUMMARY OBJECTIVE: The aim of this study was to investigate whether the degree of urbanization influences the prevalence of chronic kidney disease in Brazilian indigenous people. METHODS: This is a cross-sectional study conducted between 2016 and 2017 in northeastern Brazil and includes individuals aged between 30 and 70 years from two specific indigenous groups who volunteered to participate in the study: the Fulni-ô people (lowest degree of urbanization) and the Truká group (greater degree of urbanization). Cultural and geographical parameters were used to characterize and measure the magnitude of urbanization. We excluded individuals with known cardiovascular disease or renal failure who required hemodialysis. Chronic kidney disease was defined as a single measurement of an estimated glomerular filtration rate <60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. RESULTS: A total of 184 indigenous people from the Fulni-ô group and 96 from the Truká group with a median age of 46 years (interquartile range: 15.2) were included. We found a chronic kidney disease rate of 4.3% in the total indigenous population, generally affecting an older population: 41.7% over 60 years old (p<0.001). The Truká people had a chronic kidney disease prevalence of 6.2%, with no differences in kidney dysfunction across age groups. The Fulni-ô participants had a chronic kidney disease prevalence of 3.3%, with a higher proportion of kidney dysfunction in older participants (of the six Fulni-ô indigenous people with chronic kidney disease, five were older). CONCLUSION: Our results suggest that a higher degree of urbanization seems to negatively influence the prevalence of chronic kidney disease in Brazilian indigenous people.

Tixagevimab/cilgavimab pre-exposure prophylaxis is associated with lower breakthrough infection risk in vaccinated solid organ transplant recipients during the omicron wave.

The neutralizing monoclonal antibody combination of tixagevimab/cilgavimab has been shown to reduce the risk of SARS-CoV-2 infection in unvaccinated individuals during the Alpha (B.1.1.7) and Delta (B.1.617.2) waves. However, data on the efficacy and safety of tixagevimab/cilgavimab in vaccinated solid organ transplant recipients during the Omicron wave is limited. To address this, we conducted a retrospective cohort study comparing 222 solid organ transplant recipients (SOTRs) who received tixagevimab/cilgavimab for pre-exposure prophylaxis and 222 vaccine-matched solid organ transplant recipients who did not receive tixagevimab/cilgavimab. Breakthrough SARS-CoV-2 infections occurred in 11 (5%) of SOTRs who received tixagevimab/cilgavimab and in 32 (14%) of SOTRs in the control group (p < .001). In the tixagevimab/cilgavimab group, SOTRs who received the 150-150 mg dose had a higher incidence of breakthrough infections compared to those who received the 300-300 mg dose (p = .025). Adverse events were uncommon, occurring in 4% of our cohort and most were mild. There was no significant change in serum creatinine or liver chemistries in kidney and liver transplant recipients, respectively. In conclusion, we found that tixagevimab/cilgavimab use is safe and associated with a lower risk of breakthrough SARS-CoV-2 infection in vaccinated solid organ transplant recipients during the Omicron wave.

Evaluation of the performance of tuberculosis control actions and services of the family health strategies / Avaliação do desempenho das ações e serviços de controle da Tuberculose pela estratégia saúde da família

INTRODUCTION: Front of the persistence of tuberculosis in several municipalities in the country, the Ministry of Health (MS) established the National Tuberculosis Control Plan (NTCP), whose goals were to integrate 100% of the Brazilian municipalities in the fight against the disease. OBJECTIVE: To evaluate the performance of tuberculosis (TB) control actions and services of the Family Health Strategies in the city of Salgueiro-PE. METHOD: Cross-sectional, quantitative and descriptive survey study that evaluated health services in the city of Salgueiro-Pe, involving 40 participants. The data were selected through the steps of specific questions for the evaluation of TB, in addition to the questions on the epidemiological situation and the current state of health. In order to know the conditions for the control of TB in the municipality, a script was also elaborated with orientations directed to the manager. RESULTS: The results of our study showed a population aged from 34 to 59 years with a predominance of males (70%) and incomplete elementary school (37.5%). Regarding the place of diagnosis, the hospital had a higher prevalence of cases diagnosed with tuberculosis with 62.5%. 85,0% performed the Directly Observed Treatment. The averages of the evaluated actions showed that the municipality of Salgueiro-PE does not develop actions of health education and active search of symptomatic respiratory patients, The results were favorable only for the accomplishment of sputum bacilloscopy, monthly consultations of control and medical monitoring. CONCLUSION: The results showed weaknesses in the performance of actions and services by the Family Health Strategy in the municipality of Salgueiro, with damage to TB control and treatment.

INTRODUÇÃO: A atenção básica é resultado do desenvolvimento e consolidação do SUS através do programa de Estratégia Saúde da Família. Diante do quadro de persistência da tuberculose em vários municípios do País, o Ministério da Saúde (MS) estabeleceu o Plano Nacional de Controle da Tuberculose (PNCT) cujas metas eram integrar 100% dos municípios brasileiros na luta contra a doença. OBJETIVO: Avaliar o desempenho das ações e serviços de controle da tuberculose (TB) da Estratégia Saúde da Família no município de Salgueiro-PE. MÉTODO: Trata-se de estudo transversal, quantitativo e descritivo de inquérito que avaliou serviços de saúde na cidade de Salgueiro-PE, envolvendo 40 participantes. Os dados foram coletados através de questionário com perguntas específicas para cada componente organizacional essencial da atenção básica para as ações de controle da TB, além de perguntas sobre o perfil do paciente, informações clínicas epidemiológicas e estado atual de saúde. A fim de conhecer as políticas realizadas no controle da TB no município em estudo, foi também elaborado um roteiro com perguntas direcionadas ao gestor. RESULTADOS: Houve predominância do sexo masculino com 28 (70%), com ensino fundamental incompleto 15 (37,5%) e com faixa etária de 34 a 59 anos de idade. Quanto ao local do diagnóstico, o hospital teve maior prevalência de casos diagnosticados com tuberculose com 62,5%, os que realizavam tratamento supervisionado foram 85,0%. As médias das ações avaliadas demonstraram que o município de Salgueiro-PE não desenvolve ações de educação em saúde e busca ativa de sintomáticos respiratórios, obtendo médias favoráveis apenas para realização da baciloscopia de diagnóstico, consultas mensais de controle e acompanhamento medicamentoso. CONCLUSÃO: Houve fragilidades no desempenho das ações e serviços pela estratégia saúde da família no munícipio de Salgueiro, com prejuízos ao controle e ao tratamento, sendo necessário o fortalecimento das ações e serviços no combate à doença.