Low switched memory B cells are associated with no humoral response after SARS-CoV-2 vaccine boosters in kidney transplant recipients.

Introduction: The humoral response after SARS-CoV-2 vaccination and boosters in kidney transplant recipients (KTRs) is heterogeneous and depends on immunosuppression status. There is no validated immune measurement associated with serological response in clinical practice. Multicolor flow cytometric immunophenotyping could be useful for measuring immune response. This study aimed to study B- and T-cell compartments through Standardized EuroFlow PID Orientation after SARS-CoV-2 vaccination and their association with IgG SARS-CoV-2 seropositivity status after two doses or boosters. Methods: We conducted a multicenter prospective study to evaluate humoral response after SARS-CoV-2 vaccination in KTRs. Heterologous regimen: two doses of inactivated SARS-CoV-2 and two boosters of BNT162b2 mRNA (n=75). Homologous vaccination: two doses of BNT162b2 mRNA and one BNT162b2 mRNA booster (n=13). Booster doses were administrated to KTRs without taking into account their IgG SARS-CoV-2 seropositivity status. Peripheral blood samples were collected 30 days after the second dose and after the last heterologous or homologous booster. A standardized EuroFlow PID Orientation Tube (PIDOT) and a supervised automated analysis were used for immune monitoring cellular subsets after boosters. Results: A total of 88 KTRs were included and divided into three groups according to the time of the first detected IgG SARS-CoV-2 seropositivity: non-responders (NRs, n=23), booster responders (BRs, n=41), and two-dose responders (2DRs, n=24). The NR group was more frequent on mycophenolate than the responder groups (NRs, 96%; BRs, 80%; 2DRs, 42%; p=0.000). Switched memory B cells in the 2DR group were higher than those in the BR and NR groups (medians of 30, 17, and 10 cells/ul, respectively; p=0.017). Additionally, the absolute count of central memory/terminal memory CD8 T cells was higher in the 2DR group than in the BR and NR groups. (166, 98, and 93 cells/ul, respectively; p=0.041). The rest of the T-cell populations studied did not show a statistical difference. Conclusion: switched memory B cells and memory CD8 T-cell populations in peripheral blood were associated with the magnitude of the humoral response after SARS-CoV-2 vaccination. Boosters increased IgG anti-SARS-CoV-2 levels, CM/TM CD8 T cells, and switched MBCs in patients with seropositivity after two doses. Interestingly, no seropositivity after boosters was associated with the use of mycophenolate and a lower number of switched MBCs and CM/TM CD8 T cells in peripheral blood.

Long-term follow-up of an IgA nephropathy cohort: outcomes and risk factors.

AIM: IgA nephropathy (IgAN), the most common glomerulopathy worldwide and in Uruguay, raised treatment controversies. The study aimed to analyze long-term IgAN outcomes and treatment. METHODS: A retrospective analysis of a Uruguayan IgAN cohort, enrolled between 1985 and 2009 and followed up until 2020, was performed. The Ethics Committee approved the study. The inclusion criteria were (a) biopsy-proven IgAN; (b) age ≥12 years; and (c) available clinical, histologic, and treatment data. The patients were divided into two groups, with immunosuppressive (IS) or without (NoIS) treatment. Outcomes (end-stage kidney disease/kidney replacement therapy [ESKD/KRT] or all-cause death) were obtained from mandatory national registries. RESULTS: The study population included 241 patients (64.7% men), median age 32 (19.5) years, baseline blood pressure <130/80 mmHg in 37%, and microhematuria in 67.5% of patients. Baseline proteinuria, glomerulosclerosis, and a higher crescent percentage were significantly more frequent in the IS group. Proteinuria improved in both groups. Renal survival at 20 years was 74.6% without difference between groups. In the overall population and in the NoIS group, bivariate Cox regression analysis showed that baseline proteinuria, endocapillary hypercellularity, tubule interstitial damage, and crescents were associated with a higher risk of ESKD/KRT or death, but in the IS group, proteinuria and endocapillary hypercellularity were not. In the multivariate Cox analysis, proteinuria in the NoIS group, crescents in the IS group and tubule interstitial damage in both groups were independent risk factors. CONCLUSION: The IS group had more severe risk factors than the NoIS group but attained a similar outcome.

Poliquistosis renal autosómica dominante: ¿quiénes se benefician del tratamiento con tolvaptán?. Estado del arte / Autosomal dominant polycystic kidney disease. Who can benefit from tolvaptan therapy? State of the art / Doença renal policística autossômica dominante: quem se beneficia do tratamento com tolvaptano? Estado da arte

Resumen: La poliquistosis renal autosómica dominante es la enfermedad renal hereditaria más frecuente. Se caracteriza por la progresiva aparición de quistes renales que suelen conducir a la enfermedad renal crónica extrema en la edad adulta. La aprobación del uso de tolvaptán (antagonista del receptor V2 de la vasopresina) ha marcado un cambio significativo en el tratamiento de esta enfermedad. En los últimos años apareció evidencia que demuestra el beneficio en iniciar tratamiento con tolvaptán en pacientes que presentan una enfermedad con rápida evolución. Se realiza una revisión descriptiva de los principales estudios clínicos publicados en el periodo 2012-2022 y se sugiere un esquema de utilidad para seleccionar aquellos pacientes que pueden beneficiarse del inicio de tratamiento.

Abstract: Autosomal dominant polycystic kidney disease is the most common hereditary kidney disease. It is characterized by the progressive appearance of renal cysts that usually lead to extreme chronic kidney disease in adulthood. The approval of the use of tolvaptán (V2 vasopressin receptor antagonist) has meant a significant change in the treatment of this disease. In recent years, evidence has proved the benefits of initiating treatment with tolvaptán in patients with a rapidly evolving disease. A descriptive review of the main clinical studies published in 2012-2022 period is carried out and a useful scheme is suggested to select those patients who can benefit from the start of treatment.

Resumo: A doença renal policística autossômica dominante é a doença renal hereditária mais comum. Caracteriza-se pelo aparecimento progressivo de cistos renais que geralmente levam à doença renal crônica extrema na idade adulta. A aprovação do uso do tolvaptano (antagonista do receptor de vasopressina V2) marcou uma mudança significativa no tratamento dessa doença. Nos últimos anos, surgiram evidências que demonstram o benefício de iniciar o tratamento com tolvaptano em pacientes com doença de evolução rápida. Faz-se uma revisão descritiva dos principais estudos clínicos publicados no período 2012-2022 e sugere-se um esquema útil para selecionar aqueles pacientes que podem se beneficiar do início do tratamento.

Factores de riesgo litogénicos en obesos mórbidos en el preoperatorio de cirugía bariátrica

Resumen: Introducción: La obesidad mórbida es un factor de riesgo para litiasis renal. La cirugía bariátrica, logra buenos resultados metabólicos, pudiendo generar un aumento del riesgo de litiasis renal. Objetivo. Estudiar los factores de riesgo litogénicos en pacientes obesos en el pre operatorio de cirugía bariátrica. Metodología: Estudio descriptivo, transversal. Se incluyeron pacientes del Programa de Obesidad y Cirugía Bariátrica, de febrero de 2019 a marzo de 2020. Resultados: Se analizaron 68 pacientes, 83,3% mujeres, mediana de edad 46 (37-52) años. La mediana del IMC fue de 46 (43-53) kg/m² con un rango de 35 a 70 kg/m². De los participantes 29 (43%) eran súper-obesos (IMC>50kg/m2), 31 (48%) presentaban síndrome metabólico, 19 (28,7%) eran diabéticos, 39 (59%) eran hipertensos. La mediana del clearence de creatinina medido fue de 136,5 (100,5-162,5) ml/min, 41 (60%) pacientes fue mayor a 120 ml/min. En 16 (23%) pacientes se constató el antecedente de manifestación clínica - ecográfica de litiasis. Todos los pacientes estaban asintomáticos al momento del estudio. Encontramos al menos 1 factor litogénico en 97% pacientes y 2 en el 71%. El 60,6% tenían hiperparatiroidismo, el 63% con hipovitaminosis D ( 100 mmol/24hs, 60,3% hiperuricosuria, 48,5% tenían hipocitraturia, 42,6% hiperoxaluria, 25% hipercalciuria y 79,4% con hiperamoniuria. No se evidencio diferencias en las variables litogénicas, entre pacientes con antecedentes de litiasis y sin antecedentes, en pacientes obesos y superobesos, ni al comparar pacientes diabéticos y con síndrome metabólico vs pacientes sin estas alteraciones. Discusión y conclusiones: En nuestro estudio la alta prevalencia de factores de riesgo litogénicos, apoya el vínculo entre obesidad y la patología litiásica renal. Es aconsejable la evaluación clínica específica y la realización de un estudio litogénico previo a la cirugía bariátrica, incidiendo su resultado en la elección de la técnica quirúrgica.

Abstract: Introduction: Morbid obesity is a risk factor for kidney stones. Bariatric surgery achieves good metabolic results, and can generate an increased risk of kidney stones. Target. To study the lithogenic risk factors in obese patients in the preoperative period of bariatric surgery. Methodology: Descriptive, cross-sectional study. Patients from the Obesity and Bariatric Surgery Program were included, from February 2019 to March 2020. Results: 68 patients were analyzed, 83.3% women, median age 46 (37-52) years. The median BMI was 46 (43-53) kg/m² with a range of 35 to 70 kg/m². Of the participants, 29 (43%) were super-obese (BMI>50kg/m2), 31 (48%) had metabolic syndrome, 19 (28.7%) were diabetic, and 39 (59%) were hypertensive. The median creatinine clearance measured was 136.5 (100.5-162.5) ml/min, 41 (60%) patients were greater than 120 ml/min. In 16 (23%) patients, a history of clinical-ultrasound manifestation of lithiasis was confirmed. All patients were asymptomatic at the time of the study. We found at least 1 lithogenic factor in 97% patients and 2 in 71%. 60.6% had hyperparathyroidism, 63% with hypovitaminosis D (100 mmol/24h, 60.3% had hyperuricosuria, 48.5% had hypocitraturia, 42.6% hyperoxaluria, 25% hypercalciuria and 79.4% with hyperammoniuria. No differences were found in the lithogenic variables, between patients with a history of lithiasis and without, in obese and super obese patients, or when comparing diabetic patients and patients with metabolic syndrome vs patients without these alterations. Discussion and Conclusions: In our study, the high prevalence of lithogenic risk factors supports the link between obesity and kidney stone disease. It is advisable to carry out a specific clinical evaluation and a lithogenic study prior to bariatric surgery, with its result affecting the choice of surgical technique.

Resumo: Introdução: A obesidade mórbida é um fator de risco para cálculos renais. A cirurgia bariátrica alcança bons resultados metabólicos, podendo gerar um risco aumentado de cálculos renais. Alvo. Estudar os fatores de risco litogênicos em pacientes obesos no pré-operatório de cirurgia bariátrica. Metodologia: Estudo descritivo, transversal. Foram incluídos pacientes do Programa de Obesidade e Cirurgia Bariátrica, no período de fevereiro de 2019 a março de 2020. Resultados: Foram analisados ​​68 pacientes, 83,3% mulheres, idade mediana de 46 (37-52) anos. A mediana do IMC foi de 46 (43-53) kg/m² com variação de 35 a 70 kg/m². Dos participantes, 29 (43%) eram superobesos (IMC>50kg/m2), 31 (48%) tinham síndrome metabólica, 19 (28,7%) eram diabéticos e 39 (59%) eram hipertensos. A mediana da depuração de creatinina medida foi de 136,5 (100,5-162,5) ml/min, 41 (60%) pacientes foram maiores que 120 ml/min. Em 16 (23%) pacientes foi confirmada história de manifestação clínico-ultrassonográfica de litíase. Todos os pacientes estavam assintomáticos no momento do estudo. Encontramos pelo menos 1 fator litogênico em 97% dos pacientes e 2 em 71%. 60,6% tinham hiperparatireoidismo, 63% com hipovitaminose D (100 mmol/24h, 60,3% tinham hiperuricosúria, 48,5% tinham hipocitratúria, 42,6% hiperoxalúria, 25% hipercalciúria e 79,4% com hiperamonúria. Não foram encontradas diferenças nas variáveis litogênicas, entre pacientes com e sem história de litíase, em pacientes obesos e superobesos, ou ao comparar pacientes diabéticos e pacientes com síndrome metabólica versus pacientes sem essas alterações. Discussão e Conclusões: Em nosso estudo, a alta prevalência de fatores de risco litogênicos suporta a ligação entre obesidade e patologia de cálculos renais. Aconselha-se a realização de avaliação clínica específica e estudo litogênico prévio à cirurgia bariátrica, cujo resultado interfere na escolha da técnica cirúrgica.

Comparison of antibody response to SARS-CoV-2 after two doses of inactivated virus and BNT162b2 mRNA vaccines in kidney transplant.

BACKGROUND: Antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after mRNA or adenoviral vector-based vaccines is weak in kidney transplant (KT) patients. However, few studies have focused on humoral response after inactivated virus-based vaccines in KT. Here, we compare antibody response following vaccination with inactivated virus (CoronaVac®) and BNT162b2 mRNA. METHODS: A national multicentre cross-sectional study was conducted. The study group was composed of patients from all KT centres in Uruguay, vaccinated between 1 and 31 May 2021 (CoronaVac®, n = 245 and BNT162b2, n = 39). The control group was constituted of 82 healthy individuals. Participants had no prior confirmed coronavirus disease 2019 (COVID-19) test. Blood samples were collected between 30 and 40 days after the second dose. Serum-specific immunoglobulin G (IgG) antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 Spike protein were determined using the COVID-19 IgG QUANT ELISA Kit. RESULTS: Only 29% of KT recipients showed seroconversion (36.5% BNT162b2, 27.8% inactivated virus, P = 0.248) in comparison with 100% in healthy control with either vaccine. Antibody levels against RBD were higher with BNT162b mRNA than with inactivated virus [median (interquartile range) 173 (73-554) and 29 (11-70) binding antibody units (BAU)/mL, P < 0.034] in KT and 10 times lower than healthy control [inactivated virus: 308 (209-335) and BNT162b2: 2638 (2608-3808) BAU/mL, P < 0.034]. In multivariate analysis, variables associated with negative humoral response were age, triple immunosuppression, estimated glomerular filtration rate and time post-KT. CONCLUSION: Seroconversion was low in KT patients after vaccination with both platforms. Antibody levels against SARS-CoV-2 were lower with inactivated virus than BNT162b mRNA. These findings support the need for strategies to improve immunogenicity in KT recipients after two doses of either vaccine.

Association of Dietary Patterns with Cardiovascular and Kidney Phenotypes in an Uruguayan Population Cohort.

The impact of habitual diet on chronic diseases has not been extensively characterized in South America. We aimed to identify major dietary patterns (DP) in an adult cohort in Uruguay (Genotype Phenotype and Environment of Hypertension Study-GEFA-HT-UY) and to assess associations with metabolic, anthropometric characteristics, and cardiovascular and kidney phenotypes. In a cross-sectional study (n = 294), DP were derived by the principal component analysis. Blood and urine parameters, anthropometrics, blood pressure, pulse wave velocity, and glomerular filtration rate were measured. Multivariable adjusted linear models and adjusted binary logistic regression were used. Three DP were identified (Meat, Prudent, Cereal and Mate) explaining 22.6% of total variance in food intake. The traditional Meat DP, characterized by red and barbecued meat, processed meat, bread, and soft drinks, was associated with worse blood lipid profile. Prudent DP, characterized by vegetables, fish, and nuts, and lower loads for bread and crackers, was associated with reduced risk of vitamin D deficiency. Cereal and Mate DP, was characterized by higher loads of cereals, bread, and crackers, and mate infusion, with higher odds of excessive body weight. No direct associations of dietary patterns with hypertension, arterial stiffness, chronic kidney disease, and nephrolithiasis were found in the studied population, nor by age categories or sex.

Recertificación médica en Uruguay: múltiples miradas de una obligación impostergable / Medical recertification in Uruguay: multiple perspectives of an imperative need / Recertificação médica no Uruguai: múltiplas visões de uma obrigação urgente

Resumen: La recertificación es el resultado de un acto por el que una entidad legalmente acreditada, asegura que el profesional médico (previamente certificado) mantiene actualizados sus conocimientos y destrezas, y que ha desarrollado su actividad dentro del marco ético y científico adecuado al progreso del "saber" y del "hacer" propio de su especialidad. A pesar de un largo camino recorrido, en Uruguay no se ha podido establecer un proceso de recertificación universal. Múltiples actores (usuarios del sistema, médicos, Facultad de Medicina, programas de Desarrollo Profesional Médico Continuo) consideran que es una necesidad, sin embargo es necesario vencer algunas barreras para que se establezca un programa de recertificación. Se recorren algunos de estos aspectos en este documento, desarrollados en el contexto de un grupo de trabajo para el Congreso por los 100 años del Sindicato Médico del Uruguay.

Abstract: Recertification is the result of an act by which a legally accredited entity ensures that medical professionals (previously certified) keep their knowledge and skills up to date, and that they have practiced their profession within the ethical and scientific framework that regulates the process that evolves from "knowing" to "knowing how" in their areas of specialization. Despite a long journey in Uruguay, it has not been possible to establish a universal recertification process. Multiple actors (system users, doctors, the School of Medicine, Continuing Medical Professional Development programs) regard it as a need, although some barriers must be overcome in order to define a recertification program. This document covers a few of these aspects and is the result of a working group created for the Congress held in commemoration of the 100 years of the Uruguayan Medical Association.

Resumo: A recertificação é o resultado de um ato pelo qual uma entidade legalmente credenciada garante que o profissional médico (previamente certificado) mantém os seus conhecimentos e competências atualizados, e que desenvolveu a sua atividade dentro do quadro ético e científico adequado ao progresso do "conhecimento" e o "fazer" da sua especialidade. Apesar do longo caminho percorrido no Uruguai, ainda não foi possível estabelecer um processo de recertificação universal. Múltiplos atores (usuários do sistema, médicos, Faculdade de Medicina, programas de Desenvolvimento Continuado do Profissional Médico) consideram isso uma necessidade, porém é necessário superar algumas barreiras para que um programa de recertificação seja estabelecido. Alguns desses aspectos são abordados neste documento, desenvolvido no contexto de um grupo de trabalho para o Congresso pelos 100 anos do Sindicato Médico del Uruguay.

Recomendaciones sobre la vacunación contra SARS-CoV-2 / COVID-19 en pacientes con enfermedad renal y trasplante renal / Recommendations for the SARS-CoV-2 vaccination of patients with kidney disease and transplant recipients / Recomendações sobre vacinação contra SARS-CoV-2 / COVID-19 em pacientes com doença renal e transplante renal

Resumen: Este documento de recomendaciones tiene como objetivo orientar a médicos nefrólogos y no nefrólogos que asisten a pacientes con enfermedad renal crónica (ERC) en todas las etapas de la misma, en el proceso de vacunación contra el SARS-CoV-2. Como consecuencia de la situación epidemiológica y de los tiempos del proceso de elaboración de las vacunas disponibles, no se ha generado evidencia lo suficientemente potente, por lo que las recomendaciones no se acompañan del nivel de evidencia. Se fundamenta la necesidad de priorizar la vacunación en este grupo de pacientes en el mayor riesgo de adquirir la infección por SARS-CoV-2, desarrollar la enfermedad COVID-19 con mayor gravedad y presentar una mortalidad más elevada que la población general. Las recomendaciones se organizan por grupos de pacientes considerando pacientes con ERC no dialítica, diálisis y trasplante renal, y pacientes bajo tratamiento inmunosupresor.

Summary The objective of this document containing recommendations is to provide guidelines for nephrologists and non-nephrologists who assist patients with chronic kidney disease (CKD) at all stages of the disease on the vaccination process against SARS-CoV-2. As a consequence of the current epidemiological situation and the timing of the COVID-19 vaccine development -for available vaccines- there is no solid evidence, and thus, recommendations are not accompanied by the due medical proof. The need to prioritize vaccination in this group of patients is based on the increased risk of acquiring the SARS-CoV-2 infection, developing the COVID-19 disease with greater severity and presenting higher mortality rates than the general population. The recommendations are organized by groups of patients, considering patients with non-dialytic CKD, dialysis and kidney transplantation, and patients under immunosuppressive treatment.

Resumo: O objetivo deste documento de recomendações é orientar os nefrologistas e não nefrologistas que atendem pacientes com doença renal crônica (DRC) em todas as fases da doença, no processo de vacinação contra a SARS-CoV-2. Como consequência da situação epidemiológica e do momento do processo de produção das vacinas disponíveis, não foram geradas evidências suficientemente potentes, de modo que as recomendações não são acompanhadas de seu nível de evidência. A necessidade de priorizar a vacinação neste grupo de pacientes baseia-se no maior risco de adquirir a infecção pelo SARS-CoV-2, desenvolver a doença COVID-19 com maior gravidade e apresentar mortalidade superior à da população em geral. As recomendações são organizadas por grupos de pacientes, considerando pacientes com DRC não dialítica, em diálise, com transplante renal, e pacientes em tratamento imunossupressor.

Hemodiafiltración en línea como terapia de reemplazo renal crónica. Primera experiencia nacional en el Hospital Universitario / Online haemodiafiltration therapy to treat chronic kidney disease. First national experience in the university hospital / Hemodiafiltração on line como terapia de substituição da função renal crônica. Primeira experiência nacional no hospital universitário

Resumen: La enfermedad renal crónica tiene una prevalencia estimada de 6,5% a 8% en los adultos mayores de 18 años en Uruguay. A pesar de los esfuerzos por realizar un diagnóstico temprano y retrasar su progresión un porcentaje de pacientes requiere terapia de reemplazo renal (TRR) mediante diálisis, con una tasa de incidencia anual de 166 pacientes/millón de población. A pesar de las mejoras en el cuidado nefrológico y en las técnicas de hemodiálisis, la mortalidad anual de los pacientes en esta técnica es elevada en nuestro país (16,5%) y en todo el mundo. Con el objetivo de mejorar estos aspectos se han ensayado técnicas dialíticas que asocian la convección como estrategia para depurar moléculas de mayor tamaño que habitualmente no se depuran en la hemodiálisis convencional. La hemodiafiltración en línea (HDF-OL) es una técnica convectiva. Cuando se utiliza como TRR crónica se asocia a una reducción de la mortalidad de 30%-35% comparada con la hemodiálisis convencional. En el año 2014 se instrumentó esta técnica en el Hospital de Clínicas, siendo el centro pionero en el país en contar con ella como TRR crónico. El proceso de implementación implicó cambios de la infraestructura (monitores de diálisis, centro de tratamiento del agua), formación de recursos humanos, cambios en el funcionamiento y controles microbiológicos programados. El control de calidad sistemático y los diferentes estudios realizados en este período de cinco años han mostrado que es una técnica segura, capaz de remover solutos de tamaño medio y de disminuir los requerimientos de eritropoyetina. No se encuentra aún financiada por el sistema de salud, lo que puede constituir una barrera en su difusión a nivel nacional. En el presente trabajo se revisan las características fundamentales de la hemodiafiltración, su beneficio comparado con la hemodiálisis convencional, y el proceso de implementación de la técnica junto con algunos resultados iniciales en el Hospital de Clínicas.

Summary: Chronic kidney disease has an estimated prevalence of 6.5% to 8% in adults older than 18 years old in Uruguay. Despite efforts to make an early diagnosis and delay its progression, a percentage of patients require renal replacement therapy (RRT) with dialysis, the annual incidence rate being 166 patients per million population. Regardless of improvements in nephrology care and hemodialysis techniques, annual mortality ratex for this technique is high in our country (16.5%) and around the world. In order to improve these aspects, different dialysis techniques associating convection as a strategy to purify larger molecules that are rarely purified in conventional hemodialysis have been tried out. Online haemodiafiltration (OL-HDF) is a convective technique. When used as a chronic RRT it is associated to a 30-35% reduction in mortality compared to conventional hemodialysis. In 2014 this technique was introduced in the University Hospital, being it the first center that offered it as chronic renal replacement therapy. The implementation process implied changes in infrastructure (dialysis computer screens, water treatment center), the training of human resources, changes in the operation system and programmed microbiological controls. A systematic quality control and the different studies conducted in this 5-year period have proved it is a safe technique that removes average size solutes and reduces the erythropoietin requirements. This technique is still not funded by the health system, what may result in an obstacle for it to be applied nationally. This study reviews the main features of haemodiafiltration, its benefits when compared to conventional hemodialysis and the process needed to implement the technique, along with initial results in the University Hospital.

Resumo: No Uruguai a doença renal crônica tem uma prevalência estimada de 6.5 a 8% nos adultos maiores de 18 anos. Apesar dos esforços para realizar um diagnóstico precoce e retardar sua progressão uma porcentagem de pacientes requer terapia de substituição da função renal (TSFR) mediante diálise, com uma taxa de incidência anual de 166 pacientes/milhão de habitantes. Independentemente das melhorias na atenção nefrológica e nas técnicas de hemodiálise, a mortalidade anual dos pacientes em tratamento com esta técnica é elevada no Uruguai (16.5%) e no mundo todo. Buscando melhorar esses aspectos foram ensaiadas varias técnicas dialíticas que associam a convecção como estratégia para depurar moléculas de maior tamanho que habitualmente não são depuradas na hemodiálise convencional. A hemodiafiltração on line (HDF-OL) é uma técnica convectiva. Quando é utilizada como TSFR crônica está associada a uma redução da mortalidade de 30-35% comparada com a hemodiálise convencional. Esta técnica foi instrumentada em 2014 no Hospital de Clínicas, sendo este o centro pioneiro no Uruguai em utilizá-la como TSFR crônico. O processo de implementação impôs mudanças na infraestrutura (monitores de diálise, centro de tratamento da água), formação de Recursos Humanos e mudanças no funcionamento e controles microbiológicos programados. O controle de qualidade sistemático e os diferentes estudos realizados neste período de 5 anos mostraram que é uma técnica segura, capaz de remover solutos de tamanho médio e de reduzir os requerimentos de eritropoietina. A atual falta de financiamento pelo sistema de saúde pode ser uma barreira para sua difusão no país. Neste trabalho faz-se uma revisão das características fundamentais da hemodiafiltração, seu beneficio comparado com a hemodiálise convencional, o processo de implementação da técnica e alguns resultados iniciais do Hospital de Clínicas.

Substitution of Oral for Intravenous Cyclophosphamide in Membranous Nephropathy.

Background: Optimal immunosuppressive treatment for membranous nephropathy is still a matter of controversy. Current recommendations include oral cyclophosphamide combined with steroids (modified Ponticelli regimen) as first-line treatment in patients who are high risk. However, concerns about the cumulative toxicity of oral cyclophosphamide persist. In the last 30 years, a protocol based on low-dose intravenous cyclophosphamide plus steroids has been used to treat membranous nephropathy in Uruguay. We aimed to assess the efficacy of this regimen to induce clinical remission in patients with membranous nephropathy. Methods: In this retrospective, observational cohort study, we analyzed the outcome of 55 patients with membranous nephropathy treated between 1990 and 2017 with a 6-month course of alternating steroids (months 1, 3, and 5) plus intravenous cyclophosphamide (single dose of 15 mg/kg on the first day of months 2, 4, and 6). Results: At 24 months, 39 (71%) patients achieved clinical response with complete remission observed in 23 patients (42%) and partial remission in 16 (29%). Median time to achieve partial and complete remission was 5.9 and 11.5 months, respectively. Absence of response was observed in 16 patients (29%), five of whom started chronic RRT after a median follow-up of 3.5 years. Clinical relapse occurred in nine of 33 (27%) patients at a median of 34 months after treatment discontinuation. Conclusions: Replacement of oral cyclophosphamide with a single intravenous pulse on months 2, 4, and 6 of the modified Ponticelli regimen can be an effective and safe alternative for treatment of membranous nephropathy. Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/K360/2020_09_24_KID0002802020.mp3.

Tuberculosis en pacientes en diálisis en Uruguay / Tuberculosis in dialysis patients in Uruguay / Tuberculose em pacientes em diálise no Uruguai

Resumen: Objetivos: estimar el riesgo de tuberculosis (TB) en pacientes en terapia de reemplazo renal diálisis (TRR) y analizar la variación de la incidencia, su presentación clínica y pronóstico. Método: estudio retrospectivo desde 1995 a 2013. Los datos fueron extraídos del Registro Uruguayo de Diálisis y de la Comisión Honoraria para la Lucha Antituberculosa y Enfermedades Prevalentes (CHLA-EP). Se analizó la forma de diagnóstico, presentación clínica, prueba de tuberculina, evolución y mortalidad. Asimismo, se estudiaron variaciones de incidencia, riesgo y relación temporal con la terapia de reemplazo. Resultados: en 18 años, 10.516 pacientes recibieron diálisis crónica en Uruguay, y 13.083 casos de TB fueron diagnosticados. El 1,4% (n= 119) de todos los casos de TB en ese período fueron pacientes en TRR. La incidencia de TB en la población general en el período estudiado fue de 21 casos cada 100.000 pacientes/año (cp105) vs 212 cp105 en TRR. El riesgo de TB fue ocho veces mayor en TRR (SIR: 8, IC95% [6,5-9,3]). El tiempo medio de TRR al momento del diagnóstico fue de cuatro años (0 a 20), el 37,8% de los casos sucedieron en los dos primeros años de TRR; sin embargo, la incidencia se incrementó significativamente luego de los nueve años de TRR. La letalidad en la población general relacionada TB fue de 10,3%, siendo esta cifra duplicada en la población en TRR (23,5%). Conclusiones: el riesgo de TB en TRR es mayor y su mortalidad duplica la de la población general.

Summary: Objectives: this study aims to estimate the risk of tuberculosis in patients with renal replacement therapy (RRT) and to analyse the variation of its incidence, clinical presentation and prognosis. Method: retrospectve study from 1995 to 2013. Data was drawn from the Uruguayan Dialysis Registry and the Honorary Commission for the Fight against Tuberculosis and Prevalent Diseases (CHLA-EP). We analysed diagnosis, clinical presentation, tuberculin tests, evolution and mortality. Likewise, variations in incidence, risk and temporary relation of replacement therapy were studied. Results: in 18 years, 10,516 patients received chronic dialysis in Uruguay and 13,083 cases of tuberculosis were diagnosed. 1.4% (n= 119) of all cases of tuberculosis during that period were patients in renal replacement theraphy (RRT). The incidence of tuberculosis in the general population during the period studied was 21 every 100,000 patients/year (cp105) vs. 212 cp105 in RRT. The risk of tuberculosis was 8 times greater in RRT (SIR: 8 IC 95% (6.5; 9.3) patients. Average time of RRT at the time of diagnosis was 4 years (0 a 20), 37.8% of cases occurred in the first two years of RRT. However, incidence increased significantly after 9 years of RRT. Mortality in connection with tuberculosis in the general population was 10.3%, this figure being double in the RRT population (23.5%). Conclusions: the risk of tuberculosis in RRT is greater and its mortality doubles that of the general population.

Resumo: Objetivos: os objetivos deste estudo são 1. estimar o risco de tuberculose (TB) em pacientes em terapia de substituição renal - diálise (TSR) e 2. analisar a variação da incidência, sua apresentação clínica e prognóstico. Método: estudo retrospectivo do período 1995- 2013. Os dados foram obtidos do Registro Uruguayo de Diálisis e da Comisión Honoraria para la Lucha Antituberculosa y Enfermedades Prevalentes (CHLA-EP). Foram analisadas a forma de diagnóstico, apresentação clínica, prova de tuberculina, evolução, mortalidade e também as variações da incidência, risco e relação temporal com a TSR. Resultados: em 18 anos, 10.516 pacientes foram tratados com diálise crônica no Uruguai e foram diagnosticados 13.083 casos de TB. 1.4% (n= 119) de todos os casos de TB nesse período foram diagnosticados em pacientes em TSR. A incidência de TB na população em geral no período estudado foi de 21 cada 100.000 pacientes/ano (cp105) vs. 212 cp105 em TSR. O risco de TB foi 8 vezes maior em TSR (SIR: 8 IC 95% (6.5; 9.3). O tempo médio de TSR no momento do diagnóstico foi de 4 anos (0 a 20); 37,8% dos casos foram observados nos dos primeiros anos de TSR; no entanto, a incidência aumentou significativamente depois de 9 anos de TSR. A letalidade na população geral relacionada TB foi de 10.3%, sendo que na população em TSR esse valor se duplicou (23.5%). Conclusões: o risco de TB em TSR é maior e sua mortalidade é o dobro da observada na população geral.

IgA Nephropathy in Elderly Patients.

BACKGROUND AND OBJECTIVES: Some studies suggest that the incidence of IgA nephropathy is increasing in older adults, but there is a lack of information about the epidemiology and behavior of the disease in that age group. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective multicentric study, we analyzed the incidence, forms of presentation, clinical and histologic characteristics, treatments received, and outcomes in a cohort of 151 patients ≥65 years old with biopsy-proven IgA nephropathy diagnosed between 1990 and 2015. The main outcome was a composite end point of kidney replacement therapy or death before kidney replacement therapy. RESULTS: We found a significant increase in the diagnosis of IgA nephropathy over time from six patients in 1990-1995 to 62 in 2011-2015 (P value for trend =0.03). After asymptomatic urinary abnormalities (84 patients; 55%), AKI was the most common form of presentation (61 patients; 40%). Within the latter, 53 (86%) patients presented with hematuria-related AKI (gross hematuria and tubular necrosis associated with erythrocyte casts as the most important lesions in kidney biopsy), and eight patients presented with crescentic IgA nephropathy. Six (4%) patients presented with nephrotic syndrome. Among hematuria-related AKI, 18 (34%) patients were receiving oral anticoagulants, and this proportion rose to 42% among the 34 patients older than 72 years old who presented with hematuria-related AKI. For the whole cohort, survival rates without the composite end point were 74%, 48%, and 26% at 1, 2, and 5 years, respectively. Age, serum creatinine at presentation, and the degree of interstitial fibrosis in kidney biopsy were risk factors significantly associated with the outcome, whereas treatment with renin-angiotensin-aldosterone blockers was associated with a lower risk. Immunosuppressive treatments were not significantly associated with the outcome. CONCLUSIONS: The diagnosis of IgA nephropathy among older adults in Spain has progressively increased in recent years, and anticoagulant therapy may be partially responsible for this trend. Prognosis was poor. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_07_16_CJASNPodcast_19_08_.mp3.

Temporal trends in biopsy proven glomerular disease in Uruguay, 1990-2014.

Our aim is to describe variations in the incidence rates of glomerular disease diagnosed by renal biopsies performed in Uruguay over the last 25 years in relation to sex, age, clinical presentation and histological diagnosis. We analyzed all renal biopsies performed in Uruguay during the 25 years period and estimated incidence rates per million people per year (pmp/yr) for the population older than 14 years. Mann Kendall's trend analysis was used to assess incidence trends. In order to identify changes in trends, we compared annual incidence rates with the Joinpoint method. From 1990 to 2014, 3390 biopsies of native kidneys corresponding to glomerular disease were performed in patients older than 14 years. The average biopsy rate was 58 per pmp/yr. The glomerular disease incidence rate increased progressively over the period (p<0.05). Trends analysis over five-year periods demonstrated a progressive increase of IgA nephropathy (3.08 pmp/yr 1990-1994 to 12.53 pmp/yr 2010-2014 p<0.05), membranous nephropathy (2.38 pmp/yr 1990-1994 to 8.04 pmp/yr 2010-2014 p< 0.05) and lupus nephritis (4,23 pmp/yr 1990-1994 to 7,81 pmp/yr 2010-2014 p<0.05). There was a change in the trend of focal segmental glomerular sclerosis (FSGS) which increased until 1996 and decreased afterwards. The incidence rates of glomerular disease have doubled globally in the last quarter of a century in Uruguay, mainly related to the increase of IgA nephropathy, membranous nephropathy and lupus nephritis. There was a change in the slope of the incidence rate of FSGS.

Función renal en pacientes ambulatorios con insuficiencia cardíaca con fracción de eyección reducida; análisis de su evolución e implicancia pronóstica. Seguimiento a 4 años en una Unidad Multidisciplinaria de Insuficiencia Cardíaca / Renal function in outpatients with heart failure with reduced ejection fraction; analysis of its evolution and forecast implications. A 4 year follow up in a Multidisciplinary Unit of Heart Failure / Função renal em pacientes ambulatoriais com insuficiência cardíaca com fração de ejeção reduzida; análise de sua evolução e implicações prognósticas. Acompanhamento de até 4 anos em uma Unidade Multidisciplinar de Insuficiência Cardíaca

Resumen: Introducción: El deterioro de la función renal está asociado a un aumento de la mortalidad en los pacientes con insuficiencia cardíaca (IC). El objetivo de este estudio fue evaluar si la progresión de la enfermedad renal en pacientes estables portadores de IC con fracción de eyección reducida (ICFEr) y enfermedad renal crónica (ERC) se asocia a eventos cardiovasculares (ECV), hospitalización por IC y muerte. Metodología: Estudio de cohorte de seguimiento a 4 años, con análisis en dos etapas: tiempo 1 (inicio del estudio); y tiempo 2 (fin del estudio o muerte). Se definió ICFEr estable como IC con una fracción de eyección del ventrículo izquierdo (FEVI)<40% sin elementos de descompensación. Se definió ERC con la presencia de un filtrado glomerular estimado (FGe) < 60 ml/min/1,73 y ERC estable en ausencia de fracaso renal agudo. Resultados: Se incluyeron 94 pacientes con media de seguimiento de 37,2 meses; la edad media fue 69,5 años, 71.3% de sexo masculino. La cardiomiopatía era isquémica en 48% y la nefropatía vascular fue la predominante (62%). Se diagnosticó síndrome cardio-renal tipo 2 en 76 (81%) pacientes. Se evidenció descenso significativo del FGe entre los tiempos de análisis (tiempo 1: 45 ± 10 ml/min.; tiempo 2: 38 ± 15 ml/min.; p < 0,001) y 50% de los pacientes tuvieron peoría del estadio de ERC (p = 0,027). Se halló asociación entre progresión de la ERC con mayor frecuencia de ECV (P=0,002), ingresos por IC (OR 3,3;IC95% 1,9-11,2; p = 0.044) y muerte cardiovascular (OR 10,9;IC95% 2,9-40,1; p < 0.001). Conclusiones: La progresión de la ERC en pacientes con ICFEr ambulatorios se asocia a un peor pronóstico en términos de mortalidad cardiovascular, ingresos por IC y ECV.

Abstract: Introduction: Deterioration of renal function is associated with increased mortality in patients with heart failure (HF). The objective of the present study was to assess whether the progression of kidney disease is associated with the appearance of cardiovascular events (CVE), hospitalization for HF and death in a cohort of stable outpatients with chronic kidney disease (CKD) and Heart failure with reduced ejection fraction (HFrEF). Methodology: A 4 years follow-up cohort study, with a two stage analysis: time 1 (start of the study); and time 2 (end of study or death). Stable HFrEF was defined as HF with an ejection fraction of the left ventricle (LVEF)<40% without elements of decompensation. An estimated glomerular filtration less than 60 ml / min / 1.73 was used as diagnostic criterion for CKD and stable CKD in the absence of acute renal failure. Results: A total of 94 patients were included with a follow up mean of 37.2 months; the mean age was 69.5 years ± 9 years, 71.3% were male. Cardiomyopathy was ischemic in 48% and vascular nephropathy was predominant (62%). Cardio-renal syndrome type 2 was diagnosed in 76 (81%) patients. There was a significant decrease in eGFR between the time of analysis (time 1: 45 ± 10 ml/min, time 2: 38 ± 15 ml/min, p <0.001) and 50% of patients worsened their stage of CKD (p = 0.027). An association was found between progression of CKD with a higher frequency of CVD (P = 0.002), hospitalization for HF (OR 3.3, 95% CI 1.9-11.2, p = 0.044) and cardiovascular death (OR 10.9, 95% CI 2.9-40.1, p <0.001). Conclusions: The progression of CKD is associated with a worse prognosis in not hospitalized HF patients in terms of cardiovascular mortality, admissions for HF and CVE.

Resumo: Introdução: A deterioração da função renal está associada ao aumento da mortalidade em pacientes com insuficiência cardíaca (IC). O objectivo deste estudo foi avaliar se a progressão da doença renal em pacientes com IC estáveis ​​com fracção de ejecção reduzida (ICFER) e doença renal crónica (IRC) está associada com eventos cardiovasculares (DCV), HF hospitalização e morte. Metodologia: Estudo de coorte de acompanhamento aos 4 anos, com análise em duas etapas: tempo 1 (início do estudo); e tempo 2 (fim do estudo ou morte). O rEFFE estável foi definido como IC com fração de ejeção do ventrículo esquerdo (FEVE) <40% sem elementos de descompensação. DRC foi definida na presença de uma taxa de filtração glomerular estimada (EGFR) <60 ml / min / 1,73 CEI e estável na ausência de insuficiência renal aguda. Resultados: Foram incluídos 94 pacientes com seguimento médio de 37,2 meses; a idade média foi de 69,5 anos, 71,3% do sexo masculino. A cardiomiopatia era isquêmica em 48% e a nefropatia vascular era predominante (62%). Síndrome Cardio-renal tipo 2 foi diagnosticada em 76 (81%) pacientes. diminuição significativa da taxa de filtração glomerular entre os tempos de verificação (45 ± 10 ml / min; cerca de 2 cerca de 1 38 ± 15 ml / min; p <0,001) foi evidenciado e 50% dos pacientes tiveram a fase de Peoria DRC (p = 0,027). e morte cardiovascular (OU 10,9 associação entre a progressão DRC de DCV com maior frequência (P = 0,002), o rendimento de IC (OR 3.3, 95 % CI 1.9-11.2 p = 0,044), verificou-se IC 95% 2,9-40,1, p <0,001). Conclusões: A progressão da DRC em pacientes com HFrR ambulatorial está associada a um pior prognóstico em termos de mortalidade cardiovascular, IC e DCV

Blood Pressure in relation to 24-Hour Urinary Sodium and Potassium Excretion in a Uruguayan Population Sample.

Many public health policies in Latin America target an optimized sodium and potassium intake. The aims of this study were to assess the sodium and potassium intake using 24-hour urinary analysis and to study their association with blood pressure in a Uruguayan population cohort using cluster analysis. A total of 149 participants (aged 20-85 years) were included in the study, and office blood pressure, anthropometric measurements, biochemical parameters in the blood, and 24-hour urine samples were obtained. The overall mean sodium and potassium excretion was 152.9 ± 57.3 mmol/day (8.9 ± 3.4 g/day of salt) and 55.4 ± 19.6 mmol/day, respectively. The average office systolic/diastolic blood pressure was 124.6 ± 16.7/79.3 ± 9.9 mmHg. Three compact spherical clusters were defined in untreated participants based on predetermined attributes, including blood pressure, age, and sodium and potassium excretion. The major characteristics of the three clusters were (1) high systolic blood pressure and moderate sodium excretion, (2) moderate systolic blood pressure and very high sodium excretion, and (3) low systolic blood pressure and low sodium excretion. Participants in cluster three had systolic blood pressure values that were 23.9 mmHg (95% confidence interval: -29.5 to -1.84) lower than those in cluster one. Participants in cluster two had blood pressure levels similar to those in cluster one (P = 0.32) and worse metabolic profiles than those in cluster one and three (P < 0.05). None of the clusters showed high blood pressure levels and high sodium excretion. No linear association was found between blood pressure and urinary sodium excretion (r < 0.14; P > 0.47). An effect of sodium and potassium intake on blood pressure levels was not found at the population level using regression or cluster analysis.