Outcomes for clinical trials involving adults with chronic kidney disease: a multinational Delphi survey involving patients, caregivers, and health professionals.

BACKGROUND: Many outcomes of high priority to patients and clinicians are infrequently and inconsistently reported across trials in CKD, which generates research waste and limits evidence-informed decision making. We aimed to generate consensus among patients/caregivers and health professionals on critically important outcomes for trials in CKD prior to kidney failure and the need for kidney replacement therapy, and to describe the reasons for their choices. METHODS: Online two-round international Delphi survey. Adult patients with CKD (all stages and diagnoses), caregivers and health professionals, who could read English, Spanish, or French were eligible. Participants rated the importance of outcomes using a Likert scale (7-9 indicating critical importance) and a best-worst scale. The scores for the two groups were assessed to determine absolute and relative importance. Comments were analysed thematically. RESULTS: In total, 1 399 participants from 73 countries completed Round 1 of the Delphi survey including 628 (45%) patients/caregivers and 771 (55%) health professionals. In Round 2, 790 participants (56% response rate) from 63 countries completed the survey including 383 (48%) patients/caregivers and 407 (52%) health professionals. The overall top five outcomes were: kidney function, need for dialysis/transplant, life participation, cardiovascular disease, and death. In the final round, patients/caregivers indicated higher scores for most outcomes (17/22 outcomes), and health professionals gave higher priority to mortality, hospitalization, and cardiovascular disease (mean difference > 0.3). Consensus was based upon the two groups yielding median scores of ≥ 7 and mean scores > 7, and the proportions of both groups rating the outcome as 'critically important' being greater than 50%. Four themes reflected the reasons for their priorities: imminent threat of a health catastrophe, signifying diminishing capacities, ability to self-manage and cope, and tangible and direct consequences. CONCLUSION: Across trials in CKD, the outcomes of highest priority to patients, caregivers, and health professionals were kidney function, need for dialysis/transplant, life participation, cardiovascular disease, and death.

Unveiling the Clinical Benefits of High-Volume Hemodiafiltration: Optimizing the Removal of Medium-Weight Uremic Toxins and Beyond.

Dialysis treatment has improved the survival of patients with kidney failure. However, the hospitalization and mortality rates remain alarmingly high, primarily due to incomplete uremic toxin elimination. High-volume hemodiafiltration (HDF) has emerged as a promising approach that significantly improves patient outcomes by effectively eliminating medium and large uremic toxins, which explains its increasing adoption, particularly in Europe and Japan. Interest in this therapy has grown following the findings of the recently published CONVINCE study, as well as the need to understand the mechanisms behind the benefits. This comprehensive review aims to enhance the scientific understanding by explaining the underlying physiological mechanisms that contribute to the positive effects of HDF in terms of short-term benefits, like hemodynamic tolerance and cardiovascular disease. Additionally, it explores the rationale behind the medium-term clinical benefits, including phosphorus removal, the modulation of inflammation and oxidative stress, anemia management, immune response modulation, nutritional effects, the mitigation of bone disorders, neuropathy relief, and amyloidosis reduction. This review also analyzes the impact of HDF on patient-reported outcomes and mortality. Considering the importance of applying personalized uremic toxin removal strategies tailored to the unique needs of each patient, high-volume HDF appears to be the most effective treatment to date for patients with renal failure. This justifies the need to prioritize its application in clinical practice, initially focusing on the groups with the greatest potential benefits and subsequently extending its use to a larger number of patients.

Nephrologists' perspectives on the impact of COVID-19 on caring for patients undergoing dialysis in Latin America: a qualitative study.

OBJECTIVE: To describe the experiences of nephrologists on caring for patients undergoing in-centre haemodialysis during the COVID-19 pandemic in Latin America. DESIGN: Twenty-five semistructured interviews were conducted by Zoom videoconference in English and Spanish languages during 2020 until data saturation. Using thematic analysis, we conducted line-by-line coding to inductively identify themes. SETTING: 25 centres across nine countries in Latin America. PARTICIPANTS: Nephrologists (17 male and 8 female) were purposively sampled to include diverse demographic characteristics and clinical experience. RESULTS: We identified five themes: shock and immediate mobilisation for preparedness (overwhelmed and distressed, expanding responsibilities to manage COVID-19 infection and united for workforce resilience); personal vulnerability (being infected with COVID-19 and fear of transmitting COVID-19 to family); infrastructural susceptibility of dialysis units (lacking resources and facilities for quarantine, struggling to prevent cross-contamination, and depletion of personal protective equipment and cleaning supplies); helplessness and moral distress (being forced to ration life-sustaining equipment and care, being concerned about delayed and shortened dialysis sessions, patient hesitancy to attend to dialysis sessions, being grieved by socioeconomic disparities, deterioration of patients with COVID-19, harms of isolation and inability to provide kidney replacement therapy); and fostering innovative delivery of care (expanding use of telehealth, increasing uptake of PD and shifting focus on preventing syndemics). CONCLUSION: Nephrologists felt personally and professionally vulnerable and reported feeling helpless and morally distressed because they doubted their capacity to provide safe care for patients undergoing dialysis. Better availability and mobilisation of resources and capacities to adapt models of care, including telehealth and home-based dialysis, are urgently needed.

[Efficacy of a standardized and simplified strategy for the treatment of high blood pressure in Chile: the HEARTS Initiative in the AmericasEficácia de uma estratégia padronizada e simplificada para o tratamento da hipertensão arterial no Chile: a iniciativa HEARTS nas Américas]. / Eficacia de una estrategia estandarizada y simplificada para tratamiento de la hipertensión arterial en Chile: la Iniciativa HEARTS en las Américas.

Objective: To evaluate the effectiveness of a standardized and simplified protocol based on the technical pillars of the HEARTS Initiative for the control of hypertensive patients in the Cardiovascular Health Program at the first level of care in Chile. Methods: Longitudinal observational study (historical cohort) in two family health centers at the first level of care in Santiago. The control of blood pressure in hypertensive adults using a standardized and simplified protocol was compared to the usual protocol based on national guidelines. Innovations in the standardized protocol included changes in how the health team is coordinated, initiation of pharmacological treatment immediately after confirmed diagnosis, standardized pharmacological treatment with a combination of at least two or three antihypertensive drugs taken daily in a single tablet. Follow-up was conducted after one year to assess the percentage of adherence to treatment and achievement of blood pressure control targets (< 140/90 mmHg). Results: A total of 1490 patients were evaluated: 562 who followed the standardized and simplified protocol, and 928 who were treated with the usual protocol (family health centers: 650; family health centers: 278). After one year, patients in the standardized and simplified protocol group had a higher proportion of adherence to blood pressure control targets (65% versus 37% and 41%, p<0.001) and higher adherence to treatment compared to those following the usual protocol (71% versus 18% and 23%, p<0.001). Conclusions: The results show that the standardized and simplified protocol is more effective than the usual protocol in controlling arterial hypertension in patients undergoing treatment at the first level of care in Chile. Its implementation at the national level could contribute to a decrease in major cardiovascular events.

Objetivo: Avaliar a eficácia de um protocolo padronizado e simplificado, com base nos pilares técnicos da iniciativa HEARTS, para o controle de pacientes com hipertensão arterial do Programa de Saúde Cardiovascular na atenção primária à saúde do Chile. Métodos: Estudo observacional longitudinal (coorte histórica) em 2 centros de atenção primária de saúde da família em Santiago, que comparou o controle da pressão arterial em adultos com hipertensão, atingido com o protocolo padronizado e simplificado, versus o protocolo habitual, de acordo com as diretrizes nacionais. As inovações do protocolo padronizado incluíram mudanças na coordenação da equipe de saúde, início do tratamento farmacológico imediatamente após a confirmação do diagnóstico e tratamento farmacológico padronizado com associação de pelo menos 2 ou 3 anti-hipertensivos em um único comprimido, tomados uma vez ao dia. O acompanhamento foi realizado por 1 ano para avaliar o percentual de adesão ao tratamento e o cumprimento das metas de controle da pressão arterial (menor que 140/90 mmHg). Resultados: Foram avaliados 1.490 pacientes: 562 que utilizaram o protocolo padronizado e simplificado e 928 que foram tratados com o protocolo habitual (unidade de saúde da família 1: 650, unidade de saúde da família 2: 278). Em 1 ano de seguimento, os pacientes do grupo do protocolo padronizado e simplificado apresentaram maior proporção de cumprimento das metas de controle da pressão arterial (65% versus 37% e 41%, p<0,001) e maior percentual de adesão ao tratamento, em comparação com aqueles que utilizaram o protocolo habitual (71% versus 18% e 23%, p<0,001). Conclusões: Os resultados mostram que o protocolo padronizado e simplificado é mais eficaz que o protocolo habitual no controle da hipertensão arterial em pacientes que estão em tratamento na atenção primária do Chile. Sua implementação no nível nacional poderia contribuir para a redução de eventos cardiovasculares maiores.

Eficacia de una estrategia estandarizada y simplificada para tratamiento de la hipertensión arterial en Chile: la Iniciativa HEARTS en las Américas

[RESUMEN]. Objetivo. Evaluar la eficacia de un protocolo estandarizado y simplificado basado en los pilares técnicos de la Iniciativa HEARTS para el control de pacientes hipertensos del Programa de Salud Cardiovascular en el primer nivel de atención de salud en Chile. Métodos. Estudio observacional longitudinal (cohorte histórica), en 2 centros de salud familiar del primer nivel de atención en Santiago, que comparó el control de presión arterial en adultos hipertensos logrado con el protocolo estandarizado y simplificado, frente al protocolo habitual, según las guías nacionales. Las inno- vaciones del protocolo estandarizado incluyeron cambios en la coordinación del equipo de salud, inicio de tratamiento farmacológico inmediatamente después de confirmación diagnóstica, tratamiento farmacológico estandarizado con combinación de al menos 2 o 3 fármacos antihipertensivos en un sólo comprimido, en una toma diaria. Se realizó seguimiento por 1 año para evaluar el porcentaje de adherencia al tratamiento y cumplimiento de metas de control de presión arterial (menor a 140/90 mmHg). Resultados. Se evaluaron 1 490 pacientes: 562 que utilizaron el protocolo estandarizado y simplificado y 928 tratados con el protocolo habitual (centros de salud familiar-1: 650, centros de salud familiar -2: 278). A 1 año de seguimiento, los pacientes del grupo del protocolo estandarizado y simplificado tuvieron mayor proporción de cumplimiento de metas de control de presión arterial (65% versus 37% y 41%, p<0,001) y mayor porcen- taje de adherencia al tratamiento en comparación con aquellos con el protocolo habitual (71% versus 18% y 23%, p<0,001). Conclusiones. Los resultados muestran que el protocolo estandarizado y simplificado es más efectivo que el protocolo habitual en el control de hipertensión arterial en pacientes en tratamiento en el primer nivel de atención en Chile. Su implementación a nivel nacional podría contribuir a la disminución de eventos cardio- vasculares mayores.

[ABSTRACT]. Objective. To evaluate the effectiveness of a standardized and simplified protocol based on the technical pillars of the HEARTS Initiative for the control of hypertensive patients in the Cardiovascular Health Program at the first level of care in Chile. Methods. Longitudinal observational study (historical cohort) in two family health centers at the first level of care in Santiago. The control of blood pressure in hypertensive adults using a standardized and simplified protocol was compared to the usual protocol based on national guidelines. Innovations in the standardized protocol included changes in how the health team is coordinated, initiation of pharmacological treatment immediately after confirmed diagnosis, standardized pharmacological treatment with a combination of at least two or three antihypertensive drugs taken daily in a single tablet. Follow-up was conducted after one year to assess the percentage of adherence to treatment and achievement of blood pressure control targets (< 140/90 mmHg). Results. A total of 1490 patients were evaluated: 562 who followed the standardized and simplified protocol, and 928 who were treated with the usual protocol (family health centers: 650; family health centers: 278). After one year, patients in the standardized and simplified protocol group had a higher proportion of adherence to blood pressure control targets (65% versus 37% and 41%, p<0.001) and higher adherence to treatment com- pared to those following the usual protocol (71% versus 18% and 23%, p<0.001). Conclusions. The results show that the standardized and simplified protocol is more effective than the usual protocol in controlling arterial hypertension in patients undergoing treatment at the first level of care in Chile. Its implementation at the national level could contribute to a decrease in major cardiovascular events.

[RESUMO]. Objetivo. Avaliar a eficácia de um protocolo padronizado e simplificado, com base nos pilares técnicos da iniciativa HEARTS, para o controle de pacientes com hipertensão arterial do Programa de Saúde Cardiovas- cular na atenção primária à saúde do Chile. Métodos. Estudo observacional longitudinal (coorte histórica) em 2 centros de atenção primária de saúde da família em Santiago, que comparou o controle da pressão arterial em adultos com hipertensão, atingido com o protocolo padronizado e simplificado, versus o protocolo habitual, de acordo com as diretrizes nacionais. As inovações do protocolo padronizado incluíram mudanças na coordenação da equipe de saúde, início do tratamento farmacológico imediatamente após a confirmação do diagnóstico e tratamento farmacológico padronizado com associação de pelo menos 2 ou 3 anti-hipertensivos em um único comprimido, tomados uma vez ao dia. O acompanhamento foi realizado por 1 ano para avaliar o percentual de adesão ao trata- mento e o cumprimento das metas de controle da pressão arterial (menor que 140/90 mmHg). Resultados. Foram avaliados 1.490 pacientes: 562 que utilizaram o protocolo padronizado e simplificado e 928 que foram tratados com o protocolo habitual (unidade de saúde da família 1: 650, unidade de saúde da família 2: 278). Em 1 ano de seguimento, os pacientes do grupo do protocolo padronizado e simplificado apresentaram maior proporção de cumprimento das metas de controle da pressão arterial (65% versus 37% e 41%, p<0,001) e maior percentual de adesão ao tratamento, em comparação com aqueles que utilizaram o protocolo habitual (71% versus 18% e 23%, p<0,001). Conclusões. Os resultados mostram que o protocolo padronizado e simplificado é mais eficaz que o proto- colo habitual no controle da hipertensão arterial em pacientes que estão em tratamento na atenção primária do Chile. Sua implementação no nível nacional poderia contribuir para a redução de eventos cardiovasculares maiores.

Clinical Efficacy of SARS-CoV-2 Vaccination in Hemodialysis Patients.

Introduction: The COVID-19 pandemic is a global public health problem. Patients with end-stage renal disease on hemodialysis are at a higher risk of infection and mortality than the general population. Worldwide, a vaccination campaign has been developed that has been shown to reduce severe infections and deaths in the general population. However, there are currently limited data on the clinical efficacy of vaccinations in the hemodialysis population. Methods: A national multicenter observational cohort was performed in Chile to evaluate the clinical efficacy of anti-SARS-CoV-2 vaccination in end-stage renal disease patients on chronic hemodialysis from February 2021 to August 2021. In addition, the BNT162b2 (Pfizer-BioNTech) and CoronaVac (Sinovac) vaccines were evaluated. The efficacy of vaccination in preventing SARS-CoV-2 infection, hospitalizations, and deaths associated with COVID-19 was determined. Results: A total of 12,301 patients were evaluated; 10,615 (86.3%) received a complete vaccination (2 doses), 490 (4.0%) received incomplete vaccination, and 1196 (9.7%) were not vaccinated. During follow-up, 1362 (11.0%) patients developed COVID-19, and 150 died (case fatality rate: 11.0%). The efficacy of the complete vaccination in preventing infection was 18.1% (95% confidence interval [CI]:11.8-23.8%), and prevention of death was 66.0% (95% CI:60.6-70.7%). When comparing both vaccines, BNT162b2 and CoronaVac were effective in reducing infection and deaths associated with COVID-19. Nevertheless, the BNT162b2 vaccine had higher efficacy in preventing infection (42.6% vs. 15.0%) and deaths (90.4% vs. 64.8%) compared to CoronaVac. Conclusion: The results of our study suggest that vaccination against SARS-CoV-2 in patients on chronic hemodialysis was effective in preventing infection and death associated with COVID-19.

Survival study and factors associated with mortality in Chilean patients on peritoneal dialysis infected with SARS-CoV-2.

The Covid-19 pandemic has been responsible for millions of deaths worldwide. Patients with comorbidities- such as those on peritoneal dialysis (PD)- present higher morbidity and mortality than the general population. We prospectively evaluated all Chilean patients on PD (48 centres) and followed those who had Covid-19 from the beginning of the Covid-19 pandemic in Chile (March 2020) to January 2021 (start of vaccination campaign). We described demographic history, comorbidities, factors related to infection, need for hospitalisation and death due to Covid-19. During the study period, 106 adults on PD were infected by SARS-CoV-2, with a mean age of 53.1 (±16.3) and of which 53.9% were female. From that group, 54.8% required hospitalisation and 24.5% (n = 26) died due to Covid-19. Most of the patients (63.4%) were infected at home and 22.8% during hospitalisation for other reasons. There was a significant association for Covid-19 mortality with: being ≥60 years old, diabetes, time on PD ≥5 years, need for hospitalisation and hospital-acquired infection. At 90 days of follow-up, all deaths associated to Covid-19 occurred before 40 days. We conclude that patients on PD without Covid-19 vaccination have a high mortality and need for hospitalisation associated to Covid-19. To avoid this negative outcome, it is necessary to intensify strategies to avoid contagion, especially in those ≥60 years old, with diabetes and/or ≥5 years spent on PD.

Perspectives of patients, family members, health professionals and the public on the impact of COVID-19 on mental health.

BACKGROUND: The coronavirus (COVID-19) pandemic has seen a global surge in anxiety, depression, post-traumatic stress disorder (PTSD), and stress. AIMS: This study aimed to describe the perspectives of patients with COVID-19, their family, health professionals, and the general public on the impact of COVID-19 on mental health. METHODS: A secondary thematic analysis was conducted using data from the COVID-19 COS project. We extracted data on the perceived causes and impact of COVID-19 on mental health from an international survey and seven online consensus workshops. RESULTS: We identified four themes (with subthemes in parenthesis): anxiety amidst uncertainty (always on high alert, ebb and flow of recovery); anguish of a threatened future (intense frustration of a changed normality, facing loss of livelihood, trauma of ventilation, a troubling prognosis, confronting death); bearing responsibility for transmission (fear of spreading COVID-19 in public; overwhelming guilt of infecting a loved one); and suffering in isolation (severe solitude of quarantine, sick and alone, separation exacerbating grief). CONCLUSION: We found that the unpredictability of COVID-19, the fear of long-term health consequences, burden of guilt, and suffering in isolation profoundly impacted mental health. Clinical and public health interventions are needed to manage the psychological consequences arising from this pandemic.

Eficacia de una estrategia estandarizada y simplificada para tratamiento de la hipertensión arterial en Chile: la Iniciativa HEARTS en las Américas / Efficacy of a standardized and simplified strategy for the treatment of high blood pressure in Chile: the HEARTS Initiative in the Americas / Eficácia de uma estratégia padronizada e simplificada para o tratamento da hipertensão arterial no Chile: a iniciativa HEARTS nas Américas

RESUMEN Objetivo. Evaluar la eficacia de un protocolo estandarizado y simplificado basado en los pilares técnicos de la Iniciativa HEARTS para el control de pacientes hipertensos del Programa de Salud Cardiovascular en el primer nivel de atención de salud en Chile. Métodos. Estudio observacional longitudinal (cohorte histórica), en 2 centros de salud familiar del primer nivel de atención en Santiago, que comparó el control de presión arterial en adultos hipertensos logrado con el protocolo estandarizado y simplificado, frente al protocolo habitual, según las guías nacionales. Las innovaciones del protocolo estandarizado incluyeron cambios en la coordinación del equipo de salud, inicio de tratamiento farmacológico inmediatamente después de confirmación diagnóstica, tratamiento farmacológico estandarizado con combinación de al menos 2 o 3 fármacos antihipertensivos en un sólo comprimido, en una toma diaria. Se realizó seguimiento por 1 año para evaluar el porcentaje de adherencia al tratamiento y cumplimiento de metas de control de presión arterial (menor a 140/90 mmHg). Resultados. Se evaluaron 1 490 pacientes: 562 que utilizaron el protocolo estandarizado y simplificado y 928 tratados con el protocolo habitual (centros de salud familiar-1: 650, centros de salud familiar -2: 278). A 1 año de seguimiento, los pacientes del grupo del protocolo estandarizado y simplificado tuvieron mayor proporción de cumplimiento de metas de control de presión arterial (65% versus 37% y 41%, p<0,001) y mayor porcentaje de adherencia al tratamiento en comparación con aquellos con el protocolo habitual (71% versus 18% y 23%, p<0,001). Conclusiones. Los resultados muestran que el protocolo estandarizado y simplificado es más efectivo que el protocolo habitual en el control de hipertensión arterial en pacientes en tratamiento en el primer nivel de atención en Chile. Su implementación a nivel nacional podría contribuir a la disminución de eventos cardiovasculares mayores.

ABSTRACT Objective. To evaluate the effectiveness of a standardized and simplified protocol based on the technical pillars of the HEARTS Initiative for the control of hypertensive patients in the Cardiovascular Health Program at the first level of care in Chile. Methods. Longitudinal observational study (historical cohort) in two family health centers at the first level of care in Santiago. The control of blood pressure in hypertensive adults using a standardized and simplified protocol was compared to the usual protocol based on national guidelines. Innovations in the standardized protocol included changes in how the health team is coordinated, initiation of pharmacological treatment immediately after confirmed diagnosis, standardized pharmacological treatment with a combination of at least two or three antihypertensive drugs taken daily in a single tablet. Follow-up was conducted after one year to assess the percentage of adherence to treatment and achievement of blood pressure control targets (< 140/90 mmHg). Results. A total of 1490 patients were evaluated: 562 who followed the standardized and simplified protocol, and 928 who were treated with the usual protocol (family health centers: 650; family health centers: 278). After one year, patients in the standardized and simplified protocol group had a higher proportion of adherence to blood pressure control targets (65% versus 37% and 41%, p<0.001) and higher adherence to treatment compared to those following the usual protocol (71% versus 18% and 23%, p<0.001). Conclusions. The results show that the standardized and simplified protocol is more effective than the usual protocol in controlling arterial hypertension in patients undergoing treatment at the first level of care in Chile. Its implementation at the national level could contribute to a decrease in major cardiovascular events.

RESUMO Objetivo. Avaliar a eficácia de um protocolo padronizado e simplificado, com base nos pilares técnicos da iniciativa HEARTS, para o controle de pacientes com hipertensão arterial do Programa de Saúde Cardiovascular na atenção primária à saúde do Chile. Métodos. Estudo observacional longitudinal (coorte histórica) em 2 centros de atenção primária de saúde da família em Santiago, que comparou o controle da pressão arterial em adultos com hipertensão, atingido com o protocolo padronizado e simplificado, versus o protocolo habitual, de acordo com as diretrizes nacionais. As inovações do protocolo padronizado incluíram mudanças na coordenação da equipe de saúde, início do tratamento farmacológico imediatamente após a confirmação do diagnóstico e tratamento farmacológico padronizado com associação de pelo menos 2 ou 3 anti-hipertensivos em um único comprimido, tomados uma vez ao dia. O acompanhamento foi realizado por 1 ano para avaliar o percentual de adesão ao tratamento e o cumprimento das metas de controle da pressão arterial (menor que 140/90 mmHg). Resultados. Foram avaliados 1.490 pacientes: 562 que utilizaram o protocolo padronizado e simplificado e 928 que foram tratados com o protocolo habitual (unidade de saúde da família 1: 650, unidade de saúde da família 2: 278). Em 1 ano de seguimento, os pacientes do grupo do protocolo padronizado e simplificado apresentaram maior proporção de cumprimento das metas de controle da pressão arterial (65% versus 37% e 41%, p<0,001) e maior percentual de adesão ao tratamento, em comparação com aqueles que utilizaram o protocolo habitual (71% versus 18% e 23%, p<0,001). Conclusões. Os resultados mostram que o protocolo padronizado e simplificado é mais eficaz que o protocolo habitual no controle da hipertensão arterial em pacientes que estão em tratamento na atenção primária do Chile. Sua implementação no nível nacional poderia contribuir para a redução de eventos cardiovasculares maiores.

Standardised Outcomes in Nephrology - Chronic Kidney Disease (SONG-CKD): a protocol for establishing a core outcome set for adults with chronic kidney disease who do not require kidney replacement therapy.

BACKGROUND: Globally, over 1.2 million people die from chronic kidney disease (CKD) every year. Patients with CKD are up to 10 times more likely to die prematurely than progress to kidney failure requiring kidney replacement therapy. The burden of symptoms and impaired quality of life in CKD may be compounded by comorbidities and treatment side effects. However, patient-important outcomes remain inconsistently and infrequently reported in trials in patients with CKD, which can limit evidence-informed decision-making. The Standardised Outcomes in Nephrology - Chronic Kidney Disease (SONG-CKD) aims to establish a consensus-based core outcome set for trials in patients with CKD not yet requiring kidney replacement therapy to ensure outcomes of relevance to patients, caregivers and health professionals are consistently reported in trials. METHODS: SONG-CKD involves four phases: a systematic review to identify outcomes (domains and measures) that have been reported in randomised controlled trials involving adults with CKD who do not require kidney replacement therapy; stakeholder key informant interviews with health professionals involved in the care of adults with CKD to ascertain their views on establishing core outcomes in CKD; an international two-round online Delphi survey with patients, caregivers, clinicians, researchers, policy makers and industry representatives to obtain consensus on critically important outcome domains; and stakeholder consensus workshops to review and finalise the set of core outcome domains for trials in CKD. DISCUSSION: Establishing a core outcome set to be reported in trials in patients with CKD will enhance the relevance, transparency and impact of research to improve the lives of people with CKD. TRIAL REGISTRATION: Not applicable. This study is registered with the Core Outcome Measures in Effectiveness Trials (COMET) database: http://www.comet-initiative.org/Studies/Details/1653 .

Attended Automated Office Blood Pressure Measurement Versus Ambulatory Blood Pressure Monitoring in a Primary Healthcare Setting in Chile.

OBJECTIVES: As part of the HEARTS in the Americas initiative, Chilean primary healthcare centers have implemented novel hypertension management strategies, including new diagnostic approaches. This study evaluated the concordance between attended automated office blood pressure (AOBP) measurements with an oscillometric device and ambulatory blood pressure monitoring (ABPM). METHODS: This was an observational cohort study to evaluate and compare attended AOBP and ABPM for the diagnosis of hypertension in adults in a primary healthcare setting. RESULTS: The study evaluated 309 participants (54.2 ± 15.7 years; 50.5% male) from four primary healthcare centers in Santiago, Chile. Attended AOBP measurements were obtained at the clinic on two separate days, followed by ABPM. AOBP values indicated that 69.6% of patients had a systolic blood pressure (SBP) of ≥140 mm Hg and 34.6% had a diastolic blood pressure (DBP) of ≥90 mm Hg. A total of 83.5% had hypertension, 45.3% had high SBP, and 56.0% had high DBP. ABPM values indicated that 65.0% of patients had hypertension. The combined AOBP and ABPM analysis showed that 57.0% of patients had sustained hypertension, 26.5% had white coat hypertension, 8.1% had masked hypertension, and 8.4% were normotensive. The concordance between AOBP and ABPM (κ coefficient) was low (κ = 0.133; 95% confidence interval 0.028-0.237). The comparison of AOBP and ABPM measurements (Bland-Altman plots and bias calculations) showed an important bias in BP as measured using the AOBP method, especially for SBP (13.7 ± 11.6, 95% confidence interval -9.1 to 36.5). CONCLUSIONS: Attended AOBP alone may not be sufficient for adequate classification, diagnosis, and management of hypertension in Chile or other countries with similar demographics.

Core Outcome Measures for Trials in People With Coronavirus Disease 2019: Respiratory Failure, Multiorgan Failure, Shortness of Breath, and Recovery.

OBJECTIVES: Respiratory failure, multiple organ failure, shortness of breath, recovery, and mortality have been identified as critically important core outcomes by more than 9300 patients, health professionals, and the public from 111 countries in the global coronavirus disease 2019 core outcome set initiative. The aim of this project was to establish the core outcome measures for these domains for trials in coronavirus disease 2019. DESIGN: Three online consensus workshops were convened to establish outcome measures for the four core domains of respiratory failure, multiple organ failure, shortness of breath, and recovery. SETTING: International. PATIENTS: About 130 participants (patients, public, and health professionals) from 17 countries attended the three workshops. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Respiratory failure, assessed by the need for respiratory support based on the World Health Organization Clinical Progression Scale, was considered pragmatic, objective, and with broad applicability to various clinical scenarios. The Sequential Organ Failure Assessment was recommended for multiple organ failure, because it was routinely used in trials and clinical care, well validated, and feasible. The Modified Medical Research Council measure for shortness of breath, with minor adaptations (recall period of 24 hr to capture daily fluctuations and inclusion of activities to ensure relevance and to capture the extreme severity of shortness of breath in people with coronavirus disease 2019), was regarded as fit for purpose for this indication. The recovery measure was developed de novo and defined as the absence of symptoms, resumption of usual daily activities, and return to the previous state of health prior to the illness, using a 5-point Likert scale, and was endorsed. CONCLUSIONS: The coronavirus disease 2019 core outcome set recommended core outcome measures have content validity and are considered the most feasible and acceptable among existing measures. Implementation of the core outcome measures in trials in coronavirus disease 2019 will ensure consistency and relevance of the evidence to inform decision-making and care of patients with coronavirus disease 2019.

A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of an Omega-3 Fatty Acid Supplement in Patients With Predialysis Chronic Kidney Disease.

OBJECTIVE: Omega-3 fatty acids may reduce albuminuria and cardiovascular risk factors in patients with chronic kidney disease (CKD). We aimed to assess the effects of omega-3 fatty acid supplementation on albuminuria, blood pressure, pulse wave velocity, and inflammatory markers in patients with CKD. METHODS: Patients with CKD and a urine albumin excretion of at least 30 mg/g creatinine were supplemented for 3 months with 3,666 mg/day of docosahexaenoic and eicosapentaenoic acids or a corn oil supplement. The study was double blind. At baseline, 6 weeks, and 12 weeks, fasting blood and morning spot urine samples were obtained. Blood pressure, carotid intima media thickness, and pulse wave velocity were measured. The main outcome measure was a reduction of ≥20% in urine albumin. RESULTS: One hundred patients were randomized (50 received omega-3 fatty acids and 50 received corn oil). Four patients who received omega-3 fatty acids and 5 who received vegetable oil were lost to follow-up. In patients receiving omega-3 fatty acids, the omega-3 index increased from 3.08 (2.32-3.81) to 5.48 (3.045-7.04) percent. A 20% reduction in urine albumin excretion was observed in 13 participants of the control group and 19 participants of omega-3 group (Fisher's exact P = .274). However, the supplement had a significant and positive effect on pulse wave velocity and triglyceride level. CONCLUSION: An omega-3 fatty acid supplement of 3,666 mg/day did not modify urine albumin excretion in patients with CKD but did improve pulse wave velocity and serum triglyceride levels.

International Survey to Establish Prioritized Outcomes for Trials in People With Coronavirus Disease 2019.

OBJECTIVES: There are over 4,000 trials conducted in people with coronavirus disease 2019. However, the variability of outcomes and the omission of patient-centered outcomes may diminish the impact of these trials on decision-making. The aim of this study was to generate a consensus-based, prioritized list of outcomes for coronavirus disease 2019 trials. DESIGN: In an online survey conducted in English, Chinese, Italian, Portuguese, and Spanish languages, adults with coronavirus disease 2019, their family members, health professionals, and the general public rated the importance of outcomes using a 9-point Likert scale (7-9, critical importance) and completed a Best-Worst Scale to estimate relative importance. Participant comments were analyzed thematically. SETTING: International. SUBJECTS: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public, and health professionals (including clinicians, policy makers, regulators, funders, and researchers). INTERVENTIONS: None. MEASUREMENTS: None. MAIN RESULTS: In total, 9,289 participants from 111 countries (776 people with coronavirus disease 2019 or family members, 4,882 health professionals, and 3,631 members of the public) completed the survey. The four outcomes of highest priority for all three groups were: mortality, respiratory failure, pneumonia, and organ failure. Lung function, lung scarring, sepsis, shortness of breath, and oxygen level in the blood were common to the top 10 outcomes across all three groups (mean > 7.5, median ≥ 8, and > 70% of respondents rated the outcome as critically important). Patients/family members rated fatigue, anxiety, chest pain, muscle pain, gastrointestinal problems, and cardiovascular disease higher than health professionals. Four themes underpinned prioritization: fear of life-threatening, debilitating, and permanent consequences; addressing knowledge gaps; enabling preparedness and planning; and tolerable or infrequent outcomes. CONCLUSIONS: Life-threatening respiratory and other organ outcomes were consistently highly prioritized by all stakeholder groups. Patients/family members gave higher priority to many patient-reported outcomes compared with health professionals.

Core Outcomes Set for Trials in People With Coronavirus Disease 2019.

OBJECTIVES: The outcomes reported in trials in coronavirus disease 2019 are extremely heterogeneous and of uncertain patient relevance, limiting their applicability for clinical decision-making. The aim of this workshop was to establish a core outcomes set for trials in people with suspected or confirmed coronavirus disease 2019. DESIGN: Four international online multistakeholder consensus workshops were convened to discuss proposed core outcomes for trials in people with suspected or confirmed coronavirus disease 2019, informed by a survey involving 9,289 respondents from 111 countries. The transcripts were analyzed thematically. The workshop recommendations were used to finalize the core outcomes set. SETTING: International. SUBJECTS: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public and health professionals (including clinicians, policy makers, regulators, funders, researchers). INTERVENTIONS: None. MEASUREMENTS: None. MAIN RESULTS: Six themes were identified. "Responding to the critical and acute health crisis" reflected the immediate focus on saving lives and preventing life-threatening complications that underpinned the high prioritization of mortality, respiratory failure, and multiple organ failure. "Capturing different settings of care" highlighted the need to minimize the burden on hospitals and to acknowledge outcomes in community settings. "Encompassing the full trajectory and severity of disease" was addressing longer term impacts and the full spectrum of illness (e.g. shortness of breath and recovery). "Distinguishing overlap, correlation and collinearity" meant recognizing that symptoms such as shortness of breath had distinct value and minimizing overlap (e.g. lung function and pneumonia were on the continuum toward respiratory failure). "Recognizing adverse events" refers to the potential harms of new and evolving interventions. "Being cognizant of family and psychosocial wellbeing" reflected the pervasive impacts of coronavirus disease 2019. CONCLUSIONS: Mortality, respiratory failure, multiple organ failure, shortness of breath, and recovery are critically important outcomes to be consistently reported in coronavirus disease 2019 trials.

Adipose tissue-derived mesenchymal stromal cells for treating chronic kidney disease: A pilot study assessing safety and clinical feasibility.

BACKGROUND: Chronic kidney disease (CKD) is a growing public health concern, and available treatments are insufficient in limiting disease progression. New strategies, including regenerative cell-based therapies, have emerged as therapeutic alternatives. Results from several groups, including our own, have reported evidence of a supportive role for mesenchymal stromal cells (MSCs) in functional recovery and prevention of tissue damage in murine models of CKD. Prompted by these data, an open pilot study was conducted to assess the safety and efficacy of a single injection of autologous adipose tissue-derived MSCs (AT-MSCs) for treatment of CKD. METHODS: AT-MSCs were infused intravenously into six CKD patients at a dose of 1 million cells/kg. Patients were stabilized and followed for one year prior to MSC infusion and one year following infusion. RESULTS: No patients presented with adverse effects. Statistically significant improvement in urinary protein excretion was observed in AT-MSCs transplanted patients, from a median of 0.75 g/day (range, 0.15-9.57) at baseline to 0.54 g/day (range, 0.01-2.66) at month 12 (P = 0.046). The glomerular filtration rate was not significantly decreased post-infusion of AT-MSCs. CONCLUSION: Findings from this pilot study demonstrate that intravenous infusion of autologous expanded AT-MSCs into CKD patients was not associated with adverse effects and could benefit patients already undergoing standard medical treatment.

Efficacy of urine urea nitrogen measurement to assess the compliance with protein restricted diets / Eficacia de la medición de nitrógeno ureico urinario para evaluar la adherencia a dietas restringidas en proteínas

Background: protein restriction is the mainstay of dietary management of chronic kidney disease. Aim: to assess the usefulness of urine urea nitrogen measurement as a marker of protein restriction. Methods: healthy young participants were randomly divided in two groups. During 14 days, one group received a diet containing 30 kcal/kg body weight and 1 g protein/kg body weight and the other group received a diet with the same amount of calories and 0.6 g/kg of proteins. At baseline, seven days and 14 days, 24 h dietary recalls were answered by the participants. They collected 24 hour urine and provided spot urine samples at baseline and at the end of the intervention, to measure creatinine and urea nitrogen. Results: forty-one participants aged 29 ± 5 years completed the follow-up. According to 24h dietary recalls, the group receiving 0.6 g/kg protein reduced significantly the protein intake during the intervention from 0.88 ± 0.06 to 0.59 ± 0.05 g/kg/day. A significant reduction in 24 h urea nitrogen excretion was also observed in this group. In the group receiving 1 g/kg of protein, no significant changes in 24 h urea nitrogen excretion were observed. Among all participants, the odds ratio of observing a reduction in protein intake in the dietary survey was 5.75 (95% confidence intervals 1.29-25.55, p = 0.02), when a reduction in 24 h urea nitrogen excretion corrected by creatinine was observed. No changes were observed in urea nitrogen excretion in spot urine samples. Conclusions: repeated urea nitrogen excretion measured in 24 h urine samples can be a reliable indicator of dietary protein restriction

Introducción: la restricción proteica es fundamental en el manejo de la enfermedad renal crónica. Objetivo: evaluamos la utilidad de la medición de nitrógeno ureico urinario como marcador de restricción proteica. Métodos: participantes jóvenes sanos fueron divididos aleatoriamente en dos grupos. Un grupo recibió una dieta con 30 kcal/día/kg peso corporal y 1 g/proteína/día/kg peso corporal y el otro recibió una dieta con la misma cantidad de calorías pero con 0,6 g/kg peso corporal de proteína. Al inicio, a los siete y a los 14 días, los participantes respondieron una encuesta dietaria de recordatorio de 24 horas. Además, recolectaron orina de 24 horas y se les tomó una muestra aislada de orina al comienzo y a los 14 días de la intervención para medir creatinina y nitrógeno ureico. Resultados: cuarenta y un participantes de 29 ± 5 años completaron el estudio. El grupo que consumió 0,6 g/kg de proteínas redujo su ingesta proteica de 0,88 ± 0,06 a 0,59 ± 0,05 g/kg/día durante la intervención. En este grupo se observó una reducción significativa en la excreción urinaria de nitrógeno ureico en 24 horas. No se observó tal reducción en el grupo que consumió 1 g/kg de proteínas. La tasa de probabilidad de detectar una reducción en la ingesta proteica en las encuestas dietarias, cuando se observaba una disminución en la excreción urinaria de nitrógeno ureico/mg creatinina de 24 horas, fue de 5,75 (intervalos de confianza de 95% = 1,29-25,55, p = 0,02). No hubo cambios significativos en la excreción de nitrógeno ureico en las muestras aisladas de orina. Conclusión: las mediciones repetidas de nitrógeno ureico urinario en 24 horas son un marcador de restricción dietaria de proteínas

Efficacy of urine urea nitrogen measurement to assess the compliance with protein restricted diets.

INTRODUCTION: Background: protein restriction is the mainstay of dietary management of chronic kidney disease. Aim: to assess the usefulness of urine urea nitrogen measurement as a marker of protein restriction. Methods: healthy young participants were randomly divided in two groups. During 14 days, one group received a diet containing 30 kcal/kg body weight and 1 g protein/kg body weight and the other group received a diet with the same amount of calories and 0.6 g/kg of proteins. At baseline, seven days and 14 days, 24 h dietary recalls were answered by the participants. They collected 24 hour urine and provided spot urine samples at baseline and at the end of the intervention, to measure creatinine and urea nitrogen. Results: forty-one participants aged 29 ± 5 years completed the follow-up. According to 24h dietary recalls, the group receiving 0.6 g/kg protein reduced significantly the protein intake during the intervention from 0.88 ± 0.06 to 0.59 ± 0.05 g/kg/day. A significant reduction in 24 h urea nitrogen excretion was also observed in this group. In the group receiving 1 g/kg of protein, no significant changes in 24 h urea nitrogen excretion were observed. Among all participants, the odds ratio of observing a reduction in protein intake in the dietary survey was 5.75 (95% confidence intervals 1.29-25.55, p = 0.02), when a reduction in 24 h urea nitrogen excretion corrected by creatinine was observed. No changes were observed in urea nitrogen excretion in spot urine samples. Conclusions: repeated urea nitrogen excretion measured in 24 h urine samples can be a reliable indicator of dietary protein restriction.

INTRODUCCIÓN: Introducción: la restricción proteica es fundamental en el manejo de la enfermedad renal crónica. Objetivo: evaluamos la utilidad de la medición de nitrógeno ureico urinario como marcador de restricción proteica. Métodos: participantes jóvenes sanos fueron divididos aleatoriamente en dos grupos. Un grupo recibió una dieta con 30 kcal/día/kg peso corporal y 1 g/proteína/día/kg peso corporal y el otro recibió una dieta con la misma cantidad de calorías pero con 0,6 g/kg peso corporal de proteína. Al inicio, a los siete y a los 14 días, los participantes respondieron una encuesta dietaria de recordatorio de 24 horas. Además, recolectaron orina de 24 horas y se les tomó una muestra aislada de orina al comienzo y a los 14 días de la intervención para medir creatinina y nitrógeno ureico. Resultados: cuarenta y un participantes de 29 ± 5 años completaron el estudio. El grupo que consumió 0,6 g/kg de proteínas redujo su ingesta proteica de 0,88 ± 0,06 a 0,59 ± 0,05 g/kg/día durante la intervención. En este grupo se observó una reducción significativa en la excreción urinaria de nitrógeno ureico en 24 horas. No se observó tal reducción en el grupo que consumió 1 g/kg de proteínas. La tasa de probabilidad de detectar una reducción en la ingesta proteica en las encuestas dietarias, cuando se observaba una disminución en la excreción urinaria de nitrógeno ureico/mg creatinina de 24 horas, fue de 5,75 (intervalos de confianza de 95% = 1,29-25,55, p = 0,02). No hubo cambios significativos en la excreción de nitrógeno ureico en las muestras aisladas de orina. Conclusión: las mediciones repetidas de nitrógeno ureico urinario en 24 horas son un marcador de restricción dietaria de proteínas.

Switching Stable Kidney Transplant Recipients to a Generic Tacrolimus Is Feasible and Safe, but It Must Be Monitored.

Background. Tacrolimus is the primary immunosuppressive drug used in kidney transplant patients. Replacing brand name products with generics is a controversial issue that we studied after a Chilean Ministry of Health mandate to implement such a switch. Methods. Forty-one stable Prograf (Astellas) receiving kidney transplant patients were switched to a generic tacrolimus (Sandoz) in a 1 : 1 dose ratio and were followed up for up to 8 months. All other drugs were maintained as per normal practice. Results. Neither tacrolimus doses nor their trough blood levels changed significantly after the switch, but serum creatinine did: 1.62 ± 0.90 versus 1.75 ± 0.92 mg/dL (p < 0.001). At the same time, five graft biopsies were performed, and two of them showed cellular acute rejection. There were nine infectious episodes treated satisfactorily with proper therapies. No patient or graft was lost during the follow-up time period. Conclusion. Switching from brand name tacrolimus to a generic tacrolimus (Sandoz) is feasible and appears to be safe, but it must be monitored carefully by treating physicians.