High volume online hemodiafiltration: a global perspective and the Brazilian experience / Hemodiafiltração on-line de alto volume: uma perspectiva global e a experiência brasileira

ABSTRACT Online hemodiafiltration (HDF) is a rapidly growing dialysis modality worldwide. In Brazil, the number of patients with private health insurance undergoing HDF has exceeded the number of patients on peritoneal dialysis. The achievement of a high convection volume was associated with better clinical imprand patient - reported outcomes confirming the benefits of HDF. The HDFit trial provided relevant practical information on the implementation of online HDF in dialysis centers in Brazil. This article aims to disseminate technical information to improve the quality and safety of this new dialysis modality.

RESUMO A hemodiafiltração (HDF) on-line é uma modalidade dialítica em rápido crescimento no mundo. No Brasil, o número de pacientes com planos de saúde privados tratados por HDF já ultrapassa aquele de pacientes em diálise peritoneal. O alcance de um alto volume convectivo associado à redução de desfechos clínicos e do risco de morte confirmam os benefícios da HDF. Dados nacionais do estudo HDFit forneceram informações práticas relevantes sobre a implementação da HDF on-line em clínicas de diálise no Brasil. O objetivo desta publicação é a disseminação de informações técnicas que possam auxiliar na utilização, com qualidade e segurança, dessa nova modalidade dialítica.

Patterns of kidney function and risk assessment in a nationwide laboratory database: the Brazilian CHECK-CKD study.

BACKGROUND: Chronic kidney disease (CKD) is a global health problem with rising prevalence, morbidity, mortality, and associated costs. Early identification and risk stratification are key to preventing progression to kidney failure. However, there is a paucity of data on practice patterns of kidney function assessment to guide the development of improvement strategies, particularly in lower-income countries. METHODS: A retrospective observational analysis was conducted in a nationwide laboratory database in Brazil. We included all adult patients with at least one serum creatinine assessment between June 2018 and May 2021. Our primary objective was to determine the proportion of patients with estimated glomerular filtration rate (eGFR) evaluations accompanied by predicted levels of urinary albumin-to-creatinine ratio (pACR) assessments within 12 months. RESULTS: Out of 4,5323,332 serum creatinine measurements, 42% lacked pACR measurements within 12 months. Approximately 10.8% of tests suggested CKD, mostly at stage 3a. The proportion of serum creatinine exams paired with pACR assessment varied according to the CKD stage. Internal Medicine, Cardiology, and Obstetrics/Gynecology were the specialties requesting most of the creatinine tests. Nephrology contributed with only 1.1% of serum creatinine requests for testing. CONCLUSION: Our findings reveal that a significant proportion of individuals with a creatinine test lack an accompanying urinary albuminuria measurement in Brazil, contrary to the recommendations of the international guidelines. Non-Nephrologists perform most kidney function evaluations, even among patients with presumable advanced CKD. This highlights the urge to incorporate in clinical practice the early detection of CKD and to encourage more collaborative multidisciplinary care to improve CKD management.

Transition between peritoneal dialysis modalities: Impact on blood pressure levels and drug prescription in a national multicentric cohort.

BACKGROUND: Hypertension is a leading cause of kidney failure, affects most dialysis patients and associates with adverse outcomes. Hypertension can be difficult to control with dialysis modalities having differential effects on sodium and water removal. There are two main types of peritoneal dialysis (PD), automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD). It is unknown whether one is superior to the other in controlling blood pressure (BP). Therefore, the aim of our study was to analyse the impact of switching between these two PD modalities on BP levels in a nationally representative cohort. METHODS: This was a cohort study of patients on PD from 122 dialysis centres in Brazil (BRAZPD II study). Clinical and laboratory data were collected monthly throughout the study duration. We selected all patients who remained on PD at least 6 months and 3 months on each modality at minimum. We compared the changes in mean systolic/diastolic blood pressures (SBP/DBP) before and after modality transition using a multilevel mixed-model where patients were at first level and their clinics at the second level. RESULTS: We analysed data of 848 patients (814 starting on CAPD and 34 starting on APD). The SBP decreased by 4 (SD 22) mmHg when transitioning from CAPD to APD (p < 0.001) and increased by 4 (SD 21) mmHg when transitioning from APD to CAPD (p = 0.38); consistent findings were seen for DBP. There was no significant change in the number of antihypertensive drugs prescribed before and after transition. CONCLUSIONS: Transition between PD modalities seems to directly impact on BP levels. Further studies are needed to confirm if switching to APD could be an effective treatment for uncontrolled hypertension among CAPD patients.

High volume online hemodiafiltration: a global perspective and the Brazilian experience.

Online hemodiafiltration (HDF) is a rapidly growing dialysis modality worldwide. In Brazil, the number of patients with private health insurance undergoing HDF has exceeded the number of patients on peritoneal dialysis. The achievement of a high convection volume was associated with better clinical imprand patient - reported outcomes confirming the benefits of HDF. The HDFit trial provided relevant practical information on the implementation of online HDF in dialysis centers in Brazil. This article aims to disseminate technical information to improve the quality and safety of this new dialysis modality.

Association of Income Level and Ischemic Heart Disease: Potential Role of Walkability. / Associação de Nível de Renda e Doença Isquêmica do Coração: Papel Potencial da Caminhabilidade.

BACKGROUND: Association of Income Level and Ischemic Heart Disease: Potential Role of Walkability Association of ischemic heart disease (adjusted for traditional risk factors and socioeconomics variables) and income level (A), and walkability z-score (B), and association of walkability z-score and income level (C). BACKGROUND: Socioeconomic status has been linked to ischemic heart disease (IHD). High-income neighborhoods may expose individuals to a walking-promoting built environment for daily activities (walkability). Data from the association between income and IHD is lacking in middle-income countries. It is also uncertain whether walkability mediates this association. OBJECTIVES: To investigate whether income is associated with IHD in a middle-income country and whether neighborhood walkability mediates the income-IHD association. METHODS: This cross-sectional study evaluated 44,589 patients referred for myocardial perfusion imaging (SPECT-MPI). Income and walkability were derived from participants' residential census tract. Walkability quantitative score combined 4 variables: street connectivity, residential density, commercial density, and mixed land use. IHD was defined by abnormal myocardial perfusion during a SPECT-MPI study. We used adjusted mixed effects models to evaluate the association between income level and IHD, and we performed a mediation analysis to measure the percentage of the income-IHD association mediated by walkability. We considered p values below 0.01 as statistically significant. RESULTS: From 26,415 participants, those living in the lowest-income tertile census tract were more physically inactive (79.1% versus 75.8% versus 72.7%) when compared to higher-income tertile census tracts (p < 0.001). Income was associated with IHD (odds ratio: 0.91 [95% confidence interval: 0.87 to 0.96] for each 1,000.00 international dollars increase in income) for both men and women equally (p for interaction = 0.47). Census tracts with a higher income were associated with better walkability (p < 0.001); however, walkability did not mediate the income-IHD association (percent mediated = -0.3%). CONCLUSIONS: Income was independently associated with higher prevalence of IHD in a middle-income country irrespective of gender. Although walkability was associated with census tract income, it did not mediate the income-IHD association.

Antithrombotic regimens for the prevention of major adverse cardiac events in chronic coronary syndrome: A systematic review and network meta-analysis.

Backgroud: Antithrombotic therapy is the cornerstone of chronic coronary syndrome (CCS) management. However, the best treatment option that optimally balances bleeding risk and efficacy remains undefined. Our objective was to evaluate the effectiveness and safety of antithrombotic options and identify the optimal treatment option for patients with CCS. Methods: We used the MEDLINE, CENTRAL and Embase databases to search for randomized controlled trials with follow-up periods longer than 12 months that compared aspirin (ASA) monotherapy with other antithrombotic therapies in patients with CCS. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used. Extracted data [hazard ratios (HR)] were pooled using Bayesian fixed-effect models, allowing the estimation of credible intervals (CrI) and posterior probabilities of benefit, harm, and practical equivalence. Confidence in the results was assessed with the Confidence In Network Meta-Analysis (CINeMA) tool. The primary efficacy and safety outcomes were major adverse cardiovascular events (MACE) and primary bleeding, respectively. Secondary outcomes were acute myocardial infarction, ischemic stroke, all-cause, and cardiovascular-specific mortality. Results: Five trials with a total of 80,605 patients were included. Mean patient age ranged from 61 to 69 years, while 20.3% to 31.4% were women. The reference treatment was ASA monotherapy. ASA + prasugrel 10 mg and clopidogrel 75 mg monotherapy presented the greatest benefit for MACE [HR 0.52 (95% CrI, 0.39-0.71); and 0.68 (95% CrI, 0.54-0.88)]. There was a probability of 98.8% that ASA + ticagrelor was practically equivalent to ASA monotherapy. Regarding the primary bleeding outcome, clopidogrel 75 mg monotherapy performed best [HR 0.64 (0.42, 0.99)]. There was a probability of 97.4% that ASA + Prasugrel 10 mg increases bleeding (HR > 1.0). Secondary outcome results followed a similar treatment ranking pattern as in primary outcomes. Overall, CINeMA confidence ratings were judged as either low or very low. Conclusions: These results revealed that clopidogrel monotherapy might provide the best risk-benefit balance in treating CCS. However, low CINeMA confidence ratings may preclude more forceful conclusions. Our analysis suggests that current guidelines recommending ASA as first-line therapy for CCS management need to be revised to include additional pharmacological options.

Serum Phosphorus Level Rises in US Hemodialysis Patients Over the Past Decade: A DOPPS Special Report.

Mineral bone disorder (MBD) is a frequent consequence of chronic kidney disease, more so in patients with kidney failure treated by kidney replacement therapy. Despite the wide availability of interventions to control serum phosphate and parathyroid hormone levels, unmet gaps remain on optimal targets and best practices, leading to international practice pattern variations over time. In this Special Report, we describe international trends from the Dialysis Outcomes and Practice Patterns Study (DOPPS) for MBD biomarkers and treatments from 2002-2021, including data from a group of 7 European countries (Belgium, France, Germany, Italy, Spain, Sweden, United Kingdom), Japan, and the United States. From 2002-2012, mean phosphate levels declined in Japan (5.6 to 5.2 mg/dL), Europe (5.5 to 4.9 mg/dL), and the United States (5.7 to 5.0 mg/dL). Since then, levels rose in the United States (to mean 5.6 mg/dL, 2021), were stable in Japan (5.3 mg/dL), and declined in Europe (4.8 mg/dL). In 2021, 52% (United States), 27% (Europe), and 39% (Japan) had phosphate >5.5 mg/dL. In the United States, overall phosphate binder use was stable (80%-84% over 2015-2021), and parathyroid hormone levels rose only modestly. Although these results potentially stem from pervasive knowledge gaps in clinical practice, the noteworthy steady increase in serum phosphate in the United States over the past decades may be consequential to patient outcomes, an uncertainty that hopefully will soon be addressed by ongoing clinical trials. The DOPPS will continue to monitor international trends as new interventions and strategies ensue for MBD management in chronic kidney disease.

Gout Prevalence, Practice Patterns, and Associations with Outcomes in North American Dialysis Patients.

INTRODUCTION: Gout occurs frequently in patients with kidney disease and can lead to a significant burden on quality of life. Gout prevalence, and its association with outcomes in hemodialysis (HD) and peritoneal dialysis (PD) populations located in North America, is unknown. METHODS: We used data from North America cohorts of 70,297 HD patients (DOPPS, 2012-2020) and 5117 PD patients (PDOPPS, 2014-2020). We used three definitions of gout for this analysis: (1) having an active prescription for colchicine or febuxostat; (2) having an active prescription for colchicine, febuxostat, or allopurinol; or (3) having an active prescription for colchicine, febuxostat, or allopurinol, or prior diagnosis of gout. Propensity score matching was used to compare outcomes among patients with versus without gout. Outcomes included erythropoietin resistance index (ERI=erythropoiesis stimulating agent dose per week/(hemoglobin×weight)), all-cause mortality, hospitalization, and patient-reported outcomes (PROs). RESULTS: The gout prevalence was 13% in HD and 21% in PD; it was highest among incident dialysis patients. Description of previous history of gout was rare, and identification of gout defined by colchicine (2%-3%) or febuxostat (1%) prescription was less frequent than by allopurinol (9%-12%). Both HD and PD patients with gout (versus no gout) were older, were more likely male, had higher body mass index, and had higher prevalence of cardiovascular comorbidities. About half of patients with a gout history were prescribed urate-lowering therapy. After propensity score matching, mean ERI was 3%-6% higher for gout versus non-gout patients while there was minimal evidence of association with clinical outcomes or PROs. CONCLUSION: In a large cohort of PD and HD patients in North America, we found that gout occurs frequently and is likely under-reported. Gout was not associated with adverse clinical or PROs.

Associação de Nível de Renda e Doença Isquêmica do Coração: Papel Potencial da Caminhabilidade / Association of Income Level and Ischemic Heart Disease: Potential Role of Walkability

Resumo Fundamento O nível socioeconômico tem sido associado à doença isquêmica do coração (DIC). Bairros de alta renda podem expor os indivíduos a um ambiente construído que promova caminhadas para atividades diárias (caminhabilidade). Faltam dados sobre a associação entre renda e DIC em países de renda média. Também é incerto se a caminhabilidade medeia essa associação. Objetivos Investigar se a renda está associada à DIC em um país de renda média e se a caminhabilidade dos bairros medeia a associação entre renda e DIC. Métodos O presente estudo transversal avaliou 44.589 pacientes encaminhados para imagem de perfusão miocárdica (SPECT-MPI). A renda e a caminhabilidade foram derivadas do setor censitário residencial dos participantes. A pontuação quantitativa da caminhabilidade combinou as seguintes 4 variáveis: conectividade viária, densidade residencial, densidade comercial e uso misto do solo. A DIC foi definida pela presença de perfusão miocárdica anormal durante um estudo SPECT-MPI. Utilizamos modelos ajustados com efeitos mistos para avaliar a associação entre nível de renda e DIC e realizamos uma análise de mediação para medir o percentual da associação entre renda e DIC mediada pela caminhabilidade. Consideramos valores de p abaixo de 0,01 como estatisticamente significativos. Resultados Dos 26.415 participantes, aqueles que residiam no setor censitário do tercil de menor renda eram mais fisicamente inativos (79,1% versus 75,8% versus 72,7%) quando comparados aos setores censitários do tercil de maior renda (p < 0,001). A renda foi associada à DIC (odds ratio: 0,91 [intervalo de confiança de 95%: 0,87 a 0,96] para cada aumento de 1000,00 dólares internacionais na renda), para homens e mulheres igualmente (p para interação = 0,47). Os setores censitários com maior renda estiveram associados a uma melhor caminhabilidade (p < 0,001); no entanto, a caminhabilidade não mediou a associação entre renda e DIC (porcentagem mediada = −0,3%). Conclusões A renda foi independentemente associada a maior prevalência de DIC em um país de renda média, independentemente de gênero. Embora a caminhabilidade tenha sido associada à renda do setor censitário, ela não mediou a associação entre renda e DIC.

Abstract Background Socioeconomic status has been linked to ischemic heart disease (IHD). High-income neighborhoods may expose individuals to a walking-promoting built environment for daily activities (walkability). Data from the association between income and IHD is lacking in middle-income countries. It is also uncertain whether walkability mediates this association. Objectives To investigate whether income is associated with IHD in a middle-income country and whether neighborhood walkability mediates the income-IHD association. Methods This cross-sectional study evaluated 44,589 patients referred for myocardial perfusion imaging (SPECT-MPI). Income and walkability were derived from participants' residential census tract. Walkability quantitative score combined 4 variables: street connectivity, residential density, commercial density, and mixed land use. IHD was defined by abnormal myocardial perfusion during a SPECT-MPI study. We used adjusted mixed effects models to evaluate the association between income level and IHD, and we performed a mediation analysis to measure the percentage of the income-IHD association mediated by walkability. We considered p values below 0.01 as statistically significant. Results From 26,415 participants, those living in the lowest-income tertile census tract were more physically inactive (79.1% versus 75.8% versus 72.7%) when compared to higher-income tertile census tracts (p < 0.001). Income was associated with IHD (odds ratio: 0.91 [95% confidence interval: 0.87 to 0.96] for each 1,000.00 international dollars increase in income) for both men and women equally (p for interaction = 0.47). Census tracts with a higher income were associated with better walkability (p < 0.001); however, walkability did not mediate the income-IHD association (percent mediated = −0.3%). Conclusions Income was independently associated with higher prevalence of IHD in a middle-income country irrespective of gender. Although walkability was associated with census tract income, it did not mediate the income-IHD association.

Fatigue in incident peritoneal dialysis and mortality: A real-world side-by-side study in Brazil and the United States.

BACKGROUND: We tested if fatigue in incident Peritoneal Dialysis associated with an increased risk for mortality, independently from main confounders. METHODS: We conducted a side-by-side study from two of incident PD patients in Brazil and the United States. We used the same code to independently analyze data in both countries during 2004 to 2011. We included data from adults who completed KDQOL-SF vitality subscale within 90 days after starting PD. Vitality score was categorized in four groups: >50 (high vitality), ≥40 to ≤50 (moderate vitality), >35 to <40 (moderate fatigue), ≤35 (high fatigue; reference group). In each country's cohort, we built four distinct models to estimate the associations between vitality (exposure) and all-cause mortality (outcome): (i) Cox regression model; (ii) competing risk model accounting for technique failure events; (iii) multilevel survival model of clinic-level clusters; (iv) multivariate regression model with smoothing splines treating vitality as a continuous measure. Analyses were adjusted for age, comorbidities, PD modality, hemoglobin, and albumin. A mixed-effects meta-analysis was used to pool hazard ratios (HRs) from both cohorts to model mortality risk for each 10-unit increase in vitality. RESULTS: We used data from 4,285 PD patients (Brazil n = 1,388 and United States n = 2,897). Model estimates showed lower vitality levels within 90 days of starting PD were associated with a higher risk of mortality, which was consistent in Brazil and the United States cohorts. In the multivariate survival model, each 10-unit increase in vitality score was associated with lower risk of all-cause mortality in both cohorts (Brazil HR = 0.79 [95%CI 0.70 to 0.90] and United States HR = 0.90 [95%CI 0.88 to 0.93], pooled HR = 0.86 [95%CI 0.75 to 0.98]). Results for all models provided consistent effect estimates. CONCLUSIONS: Among patients in Brazil and the United States, lower vitality score in the initial months of PD was independently associated with all-cause mortality.

Clinical performance, intermediate and long-term outcomes of high-volume hemodiafiltration in patients with kidney failure.

Hemodiafiltration (HDF), in which both convective and diffusion methods are combined, yields an increased overall solute clearance compared with hemodialysis (HD), specifically for medium and larger molecular weight uremic toxins. Due to uncertainty in the treatment effects, the nephrology community still perceives the implementation of HDF and the achievement of high convective volume as complex. In this article, we review practical aspects of the implementation of HDF that can effectively deliver a high-volume HDF therapy and assure clinical performance to most patients. We also present an overview of the impact of high-volume HDF (compared to HD) on a series of relevant biochemical, patient-reported, and clinical outcomes, including uremic toxin removal, phosphate, Inflammation and oxidative stress, hemodynamic stability, cardiac outcomes, nutritional effects, health-related quality of life, morbidity, and mortality.

High-volume hemodiafiltration decreases the pre-dialysis concentrations of indoxyl sulfate and p-cresyl sulfate compared to hemodialysis: a post-hoc analysis from the HDFit randomized controlled trial.

BACKGROUND: Although high-volume online hemodiafiltration has been associated with higher clearance and lower pre-dialysis concentration of middle molecular weight toxins compared to hemodialysis, its effect on protein-bound uremic toxins has shown inconclusive results. In this study, we investigated whether hemodiafiltration impacts pre-dialysis plasma levels of the toxins indoxyl sulfate, p-cresyl sulfate, and indole-3-acetic acid compared to high-flux hemodialysis. METHODS: This is a post-hoc analysis of the multicenter, randomized controlled trial HDFit (ClinicalTrials.gov: NCT02787161). Uremic toxins were determined by high performance liquid chromatography at baseline, 3, and 6 months. Mean differences in monthly changes of pre-dialysis uremic toxin concentrations between hemodiafiltration and high-flux hemodialysis were analyzed using linear mixed-effect models. RESULTS: One hundred ninety-three patients (mean age 53 years old, 71% males) were analyzed. There were no differences between groups regarding clinical and biochemical characteristics at baseline or duration of dialysis session and blood flows throughout the follow-up. Mean differences in rates of change (µM/month, [confidence interval CI]) in high-flux hemodialysis vs. hemodiafiltration were 2.4 [0.3 to 4.56], 3.94 [- 1.54 to 9.41] and 0.06 [- 0.6 to 0.5] for indoxyl sulfate, p-cresyl sulfate and indole-3-acetic acid, respectively. In the exploratory analysis, these differences in high-flux hemodialysis vs. hemodiafiltration subgroup with convective volume > 27.5 L were 2.86 [0.43 to 5.28], 7.43 [0.7 to 14.16] and - 0.19 [- 0.88 to 0.50]. CONCLUSION: These exploratory findings suggest that hemodiafiltration is more effective in reducing indoxyl sulfate as compared to standard high-flux hemodialysis, and also that this effect was extended to p-cresyl sulfate in patients achieving higher convective volumes.

Can we cure diabetic kidney disease? Present and future perspectives from a nephrologist's point of view.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) worldwide, contributing to a great burden across a variety of patient-reported and clinical outcomes. New interventions for DKD management have been established in recent years, unleashing a novel paradigm, in which kidney-dedicated trials yield informative and robust data to guide optimal clinical management. After unprecedented results from groundbreaking randomized controlled trials were released, a new scenario of evidence-based recommendations has evolved for the management of diabetic patients with CKD. The current guidelines place great emphasis on multidimensional and interdisciplinary approaches, but the challenges of implementation are just starting and will be pivotal to optimize clinical results and to understand the new threshold for residual risk in DKD. We thereby provide an updated review on recent advances in DKD management based on new guideline recommendations, summarizing recent evidence while projecting the landscape for innovative ongoing initiatives in the field. Specifically, we review current insights on the natural history, epidemiology, pathogenesis, and therapeutics of DKD, mapping the new scientific information into the recently released Kidney Disease - Improving Global Outcomes Guidelines translating results from major novel randomized controlled trials to the clinical practice. Additionally, we approach the landscape of new therapeutics in the field, summarizing ongoing phase IIb and III trials focused on DKD. Finally, reflecting on the past and looking into the future, we highlight unmet needs in the current DKD management based on real-world evidence and offer a nephrologist's perspective into the challenge of fostering continuous improvement on clinical and patient-reported outcomes for individuals living with DKD.

Peritoneal dialysis modality transition and impact on phosphate and potassium serum levels.

Peritoneal dialysis (PD) modalities affect solute removal differently. However, the impacts of switching PD modalities on serum levels of biomarkers of different sizes are not known. Our objective was to analyze whether a change in the PD modality associates with the levels of two routine biochemical laboratories. In this multicentric prospective cohort study. we selected all patients who remained on a PD modality for at least 6 months and switched PD modality. Patients were also required to be treated with the same PD modality for at least 3 months before and after the modality change. The primary outcome was change in potassium and phosphate serum levels. We identified 737 eligible patients who switched their PD modality during the study. We found mean serum phosphate levels increased during the 3 months after switching from CAPD to APD and conversely decreased after switching to from APD to CAPD. In contrast, for potassium the difference in the mean serum levels was comparable between groups switching from CAPD to APD, and vice versa. In conclusion, CAPD seems to be as efficient as APD for the control of potassium serum levels, but more effective for the control of phosphate serum levels. The effect of a higher removal of middle size molecules as result of PD modalities in terms of clinical and patient-reported outcomes should be further explored.

COVID-19 in Brazil-Preliminary Analysis of Response Supported by Artificial Intelligence in Municipalities.

The novel coronavirus disease (COVID-19) forced rapid adaptations in the way healthcare is delivered and coordinated by health systems. Brazil has a universal public health system (Sistema Unico de Saúde-SUS), being the main source of care for 75% of the population. Therefore, a saturation of the system was foreseen with the continuous increase of cases. The use of Artificial Intelligence (AI) to empower telehealth could help to tackle this by increasing a coordinated patient access to the health system. In the present study we describe a descriptive case report analyzing the use of Laura Digital Emergency Room-an AI-powered telehealth platform-in three different cities. It was computed around 130,000 interactions made by the chatbot and 24,162 patients completed the digital triage. Almost half (44.8%) of the patients were classified as having mild symptoms, 33.6% were classified as moderate and only 14.2% were classified as severe. The implementation of an AI-powered telehealth to increase accessibility while maintaining safety and leveraging value amid the unprecedent impact of the COVID-19 pandemic was feasible in Brazil and may reduce healthcare overload. New efforts to yield sustainability of affordable and scalable solutions are needed to truly leverage value in health care systems, particularly in the context of middle-low-income countries.

Serum Biomarkers of Iron Stores Are Associated with Increased Risk of All-Cause Mortality and Cardiovascular Events in Nondialysis CKD Patients, with or without Anemia.

BACKGROUND: Approximately 30%-45% of patients with nondialysis CKD have iron deficiency. Iron therapy in CKD has focused primarily on supporting erythropoiesis. In patients with or without anemia, there has not been a comprehensive approach to estimating the association between serum biomarkers of iron stores, and mortality and cardiovascular event risks. METHODS: The study included 5145 patients from Brazil, France, the United States, and Germany enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study, with first available transferrin saturation (TSAT) and ferritin levels as exposure variables. We used Cox models to estimate hazard ratios (HRs) for all-cause mortality and major adverse cardiovascular events (MACE), with progressive adjustment for potentially confounding variables. We also used linear spline models to further evaluate functional forms of the exposure-outcome associations. RESULTS: Compared with patients with a TSAT of 26%-35%, those with a TSAT ≤15% had the highest adjusted risks for all-cause mortality and MACE. Spline analysis found the lowest risk at TSAT 40% for all-cause mortality and MACE. Risk of all-cause mortality, but not MACE, was also elevated at TSAT ≥46%. Effect estimates were similar after adjustment for hemoglobin. For ferritin, no directional associations were apparent, except for elevated all-cause mortality at ferritin ≥300 ng/ml. CONCLUSIONS: Iron deficiency, as captured by TSAT, is associated with higher risk of all-cause mortality and MACE in patients with nondialysis CKD, with or without anemia. Interventional studies evaluating the effect on clinical outcomes of iron supplementation and therapies for alternative targets are needed to better inform strategies for administering exogenous iron.

A real-world longitudinal study of anemia management in non-dialysis-dependent chronic kidney disease patients: a multinational analysis of CKDopps.

Previously lacking in the literature, we describe longitudinal patterns of anemia prescriptions for non-dialysis-dependent chronic kidney disease (NDD-CKD) patients under nephrologist care. We analyzed data from 2818 Stage 3-5 NDD-CKD patients from Brazil, Germany, and the US, naïve to anemia medications (oral iron, intravenous [IV] iron, or erythropoiesis stimulating agent [ESA]) at enrollment in the CKDopps. We report the cumulative incidence function (CIF) of medication initiation stratified by baseline characteristics. Even in patients with hemoglobin (Hb) < 10 g/dL, the CIF at 12 months for any anemia medication was 40%, and 28% for ESAs. Patients with TSAT < 20% had a CIF of 26% and 6% for oral and IV iron, respectively. Heart failure was associated with earlier initiation of anemia medications. IV iron was prescribed to < 10% of patients with iron deficiency. Only 40% of patients with Hb < 10 g/dL received any anemia medication within a year. Discontinuation of anemia treatment was very common. Anemia treatment is initiated in a limited number of NDD-CKD patients, even in those with guideline-based indications to treat. Hemoglobin trajectory and a history of heart failure appear to guide treatment start. These results support the concept that anemia is sub-optimally managed among NDD-CKD patients in the real-world setting.

Achieving high convective volume in hemodiafiltration: Lessons learned after successful implementation in the HDFit trial.

BACKGROUND AND OBJECTIVES: High-volume online hemodiafiltration (OL-HDF) associates with improved outcomes compared to hemodialysis (HD), provided adequate dosing is achieved as estimated from convective volume (CV). Achievement of high CV and its impact on biochemical indicators following a standardized protocol converting HD patients to OL-HDF has not been systematically reported. We assessed the success of implementation of OL-HDF in clinics naïve to the modality. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We analyzed the results of the implementation of postdilution OL-HDF in patients randomized to the HDF arm of a clinical trial (impact of hemoDiaFIlTration on physical activity and self-reported outcomes: a randomized controlled trial (HDFit) trial [ClinicalTrials.gov:NCT02787161]). The day before randomization of the first patient to OL-HDF at each clinic staff started a 3-day in-person training module on operation of Fresenius 5008 CorDiax machine in HDF mode. Patients were converted from high-flux HD to OL-HDF under oversight of trainers. OL-HDF was performed over a 6-months follow-up with a CV target of 22 L/treatment. We characterized median achieved CV >22 L/treatment record and analyzed the impact of HDF on biochemical variables. RESULTS: Ninety-seven patients (mean age 53 ± 16 years, 29% with diabetes, and 11% had a catheter) from 13 clinics randomized to the OL-HDF arm of the trial were converted from HD to HDF. Median CV > 22 L/treatment was achieved in 99% (94/95) of OL-HDF patients throughout follow-up. Monthly mean CV ranged from 27.1 L to 27.5 L. OL-HDF provided an increased single pool Kt/V at 3-months (0.2 [95% CI: 0.1-0.3]) and 6-months (0.2 [95% CI: 0.1-0.4]) compared to baseline, and reduced phosphate at 3-months (-0.4 mg/dL [95% CI: -0.8 to -0.12]) of follow-up. CONCLUSIONS: High-volume online hemodiafiltration was successfully implemented with 99% of patients achieving protocol defined CV target. Monthly mean CV was consistently >22 L/treatment during follow-up. Kt/V increased, and phosphate decreased with OL-HDF. Findings resulting from a short training period in several dialysis facilities appear to suggest HDF is an easily implementable technique.

Effect of hemodiafiltration on measured physical activity: primary results of the HDFIT randomized controlled trial.

BACKGROUND: Dialysis patients are typically inactive and their physical activity (PA) decreases over time. Uremic toxicity has been suggested as a potential causal factor of low PA in dialysis patients. Post-dilution high-volume online hemodiafiltration (HDF) provides greater higher molecular weight removal and studies suggest better clinical/patient-reported outcomes compared with hemodialysis (HD). METHODS: HDFIT was a randomized controlled trial at 13 clinics in Brazil that aimed to investigate the effects of HDF on measured PA (step counts) as a primary outcome. Stable HD patients (vintage 3-24 months) were randomized to receive HDF or high-flux HD. Treatment effect of HDF on the primary outcome from baseline to 3 and 6 months was estimated using a linear mixed-effects model. RESULTS: We randomized 195 patients (HDF 97; HD 98) between August 2016 and October 2017. Despite the achievement of a high convective volume in the majority of sessions and a positive impact on solute removal, the treatment effect HDF on the primary outcome was +538 [95% confidence interval (CI) -330 to 1407] steps/24 h after dialysis compared with HD, and was not statistically significant. Despite a lack of statistical significance, the observed size of the treatment effect was modest and driven by steps taken between 1.5 and 24.0 h after dialysis, in particular between 20 and 24 h (+197 steps; 95% CI -95 to 488). CONCLUSIONS: HDF did not have a statistically significant treatment effect on PA 24 h following dialysis, albeit effect sizes may be clinically meaningful and deserve further investigation.