Hybrid Therapies for Supporting Critically Ill Patients with Acute Kidney Injury: When, how, and for Whom?

UNASSIGNED: Acute kidney injury (AKI) is common in critically ill patients. There is no specific pharmacological treatment for established severe AKI. Therefore, the conventional therapeutic strategy is limited to the use of kidney replacement therapy (KRT) to maintain homeostasis. Hybrid therapies optimize the advantages of intermittent and continuous modalities of KRT, combining lower hourly efficiency, longer application time, at lesser cost, but also adding different physicochemical principles of extracorporeal clearance. The sum of convection and diffusion, with or without adsorption or apheresis, and in different time combinations gives hybrid techniques great flexibility in prescribing a personalized treatment adapted to the needs of each patient at any given time. Hybrid therapies are increasingly being used due to their flexibility, which is determined by the combination of equipment, membranes, and available resources (machines and health-care personnel experience). The required technology is widely available in most intensive care units and uses low-cost consumables compared to other types of AKI treatment modalities, favoring its widespread use. Hybrid therapies are feasible and provide a viable form of KRT, either alone or as a transition therapy from continuous kidney replacement therapy to intermittent hemodialysis. (Rev Invest Clin. 2023;75(6):337-47).

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.

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.

Hybrid Therapies for Supporting Critically Ill Patients with Acute Kidney Injury: When, how, and for Whom?

ABSTRACT Acute kidney injury (AKI) is common in critically ill patients. There is no specific pharmacological treatment for established severe AKI. Therefore, the conventional therapeutic strategy is limited to the use of kidney replacement therapy (KRT) to maintain homeostasis. Hybrid therapies optimize the advantages of intermittent and continuous modalities of KRT, combining lower hourly efficiency, longer application time, at lesser cost, but also adding different physicochemical principles of extracorporeal clearance. The sum of convection and diffusion, with or without adsorption or apheresis, and in different time combinations gives hybrid techniques great flexibility in prescribing a personalized treatment adapted to the needs of each patient at any given time. Hybrid therapies are increasingly being used due to their flexibility, which is determined by the combination of equipment, membranes, and available resources (machines and health-care personnel experience). The required technology is widely available in most intensive care units and uses low-cost consumables compared to other types of AKI treatment modalities, favoring its widespread use. Hybrid therapies are feasible and provide a viable form of KRT, either alone or as a transition therapy from continuous kidney replacement therapy to intermittent hemodialysis.

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.