Digital Health Support: Current Status and Future Development for Enhancing Dialysis Patient Care and Empowering Patients.

Chronic kidney disease poses a growing global health concern, as an increasing number of patients progress to end-stage kidney disease requiring kidney replacement therapy, presenting various challenges including shortage of care givers and cost-related issues. In this narrative essay, we explore innovative strategies based on in-depth literature analysis that may help healthcare systems face these challenges, with a focus on digital health technologies (DHTs), to enhance removal and ensure better control of broader spectrum of uremic toxins, to optimize resources, improve care and outcomes, and empower patients. Therefore, alternative strategies, such as self-care dialysis, home-based dialysis with the support of teledialysis, need to be developed. Managing ESKD requires an improvement in patient management, emphasizing patient education, caregiver knowledge, and robust digital support systems. The solution involves leveraging DHTs to automate HD, implement automated algorithm-driven controlled HD, remotely monitor patients, provide health education, and enable caregivers with data-driven decision-making. These technologies, including artificial intelligence, aim to enhance care quality, reduce practice variations, and improve treatment outcomes whilst supporting personalized kidney replacement therapy. This narrative essay offers an update on currently available digital health technologies used in the management of HD patients and envisions future technologies that, through digital solutions, potentially empower patients and will more effectively support their HD treatments.

A new era in the science and care of kidney diseases.

Notable progress in basic, translational and clinical nephrology research has been made over the past five decades. Nonetheless, many challenges remain, including obstacles to the early detection of kidney disease, disparities in access to care and variability in responses to existing and emerging therapies. Innovations in drug development, research technologies, tissue engineering and regenerative medicine have the potential to improve patient outcomes. Exciting prospects include the availability of new drugs to slow or halt the progression of chronic kidney disease, the development of bioartificial kidneys that mimic healthy kidney functions, and tissue engineering techniques that could enable transplantable kidneys to be created from the cells of the recipient, removing the risk of rejection. Cell and gene therapies have the potential to be applied for kidney tissue regeneration and repair. In addition, about 30% of kidney disease cases are monogenic and could potentially be treated using these genetic medicine approaches. Systemic diseases that involve the kidney, such as diabetes mellitus and hypertension, might also be amenable to these treatments. Continued investment, communication, collaboration and translation of innovations are crucial to realize their full potential. In addition, increasing sophistication in exploring large datasets, implementation science, and qualitative methodologies will improve the ability to deliver transformational kidney health strategies.

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.

Network analysis of spread of SARS-CoV-2 within dialysis clinics: A multi-center network analysis.

BACKGROUND: In-center hemodialysis entails repeated interactions between patients and clinic staff, potentially facilitating the spread of COVID-19. We examined if in-center hemodialysis is associated with the spread of SARS-CoV-2 between patients. METHODS: Our retrospective analysis comprised all patients receiving hemodialysis in four New York City clinics between March 12th, 2020, and August 31st, 2022. Treatment-level clinic ID, dialysis shift, dialysis machine station, and date of COVID-19 diagnosis by RT-PCR were documented. To estimate the donor-to-potential recipient exposure ("donor" being the COVID-19 positive patient denoted as "COV-Pos"; "potential recipient" being other susceptible patients in the same shift), we obtained the spatial coordinates of each dialysis station, calculated the Euclidean distances between stations and weighted the exposure by proximity between them. For each donor, we estimated the donor-to-potential recipient exposure of all potential recipients dialyzed in the same shift and accumulated the exposure over time within the 'COV-Pos infectious period' as cumulative exposures. The 'COV-Pos infectious period' started 5 days before COVID-19 diagnosis date. We deployed network analysis to assess these interactions and summarized the donor-to-potential recipient exposure in 193 network diagrams. We fitted mixed effects logistic regression models to test whether more donor-to-potential recipient exposure conferred a higher risk of SARS-CoV-2 infection. RESULTS: Out of 978 patients, 193 (19.7%) tested positive for COVID-19 and had contact with other patients during the COV-Pos infectious period. Network diagrams showed no evidence that more exposed patients would have had a higher chance of infection. This finding was corroborated by logistic mixed effect regression (donor-to-potential recipient exposure OR: 0.63; 95% CI 0.32 to 1.17, p = 0.163). Separate analyses according to vaccination led to materially identical results. CONCLUSIONS: Transmission of SARS-CoV-2 between in-center hemodialysis patients is unlikely. This finding supports the effectiveness of non-pharmaceutical interventions, such as universal masking and other procedures to control spread of COVID-19.

Patient Survival With Extended Home Hemodialysis Compared to In-Center Conventional Hemodialysis.

Introduction: More frequent and/or longer hemodialysis (HD) has been associated with improvements in numerous clinical outcomes in patients on dialysis. Home HD (HHD), which allows more frequent and/or longer dialysis with lower cost and flexibility in treatment planning, is not widely used worldwide. Although, retrospective studies have indicated better survival with HHD, this issue remains controversial. In this multicenter study, we compared thrice-weekly extended HHD with in-center conventional HD (ICHD) in a large patient population with a long-term follow-up. Methods: We matched 349 patients starting HHD between 2010 and 2014 with 1047 concurrent patients on ICHD by using propensity scores. Patients were followed-up with from their respective baseline until September 30, 2018. The primary outcome was overall survival. Secondary outcomes were technique survival; hospitalization; and changes in clinical, laboratory, and medication parameters. Results: The mean duration of dialysis session was 418 ± 54 minutes in HHD and 242 ± 10 minutes in patients on ICHD. All-cause mortality rate was 3.76 and 6.27 per 100 patient-years in the HHD and the ICHD groups, respectively. In the intention-to-treat analysis, HHD was associated with a 40% lower risk for all-cause mortality than ICHD (hazard ratio [HR] = 0.60; 95% confidence interval [CI] 0.45 to 0.80; P < 0.001). In HHD, the 5-year technical survival was 86.5%. HHD treatment provided better phosphate and blood pressure (BP) control, improvements in nutrition and inflammation, and reduction in hospitalization days and medication requirement. Conclusion: These results indicate that extended HHD is associated with higher survival and better outcomes compared to ICHD.

Testing of worn face mask and saliva for SARS-CoV-2.

Background: Exhaled SARS-CoV-2 can be detected on face masks. We compared tests for SARS-CoV-2 RNA on worn face masks and matched saliva samples. Methods: We conducted this prospective, observational, case-control study between December 2021 and March 2022. Cases comprised 30 in-center hemodialysis patients with recent COVID-19 diagnosis. Controls comprised 13 hemodialysis patients and 25 clinic staff without COVID-19 during the study period and the past 2 months. Disposable 3-layer masks were collected after being worn for 4 hours together with concurrent saliva samples. ThermoFisher COVID-19 Combo Kit (A47814) was used for RT-PCR testing. Results: Mask and saliva testing specificities were 99% and 100%, respectively. Test sensitivity was 62% for masks, and 81% for saliva (p = 0.16). Median viral RNA shedding duration was 11 days and longer in immunocompromised versus non-immunocompromised patients (22 vs. 11 days, p = 0.06, log-rank test). Conclusion: While SARS-CoV-2 testing on worn masks appears to be less sensitive compared to saliva, it may be a preferred screening method for individuals who are mandated to wear masks yet averse to more invasive sampling. However, optimized RNA extraction methods and automated procedures are warranted to increase test sensitivity and scalability. We corroborated longer viral RNA shedding in immunocompromised patients.

Predicting SARS-CoV-2 infection among hemodialysis patients using multimodal data.

Background: The coronavirus disease 2019 (COVID-19) pandemic has created more devastation among dialysis patients than among the general population. Patient-level prediction models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are crucial for the early identification of patients to prevent and mitigate outbreaks within dialysis clinics. As the COVID-19 pandemic evolves, it is unclear whether or not previously built prediction models are still sufficiently effective. Methods: We developed a machine learning (XGBoost) model to predict during the incubation period a SARS-CoV-2 infection that is subsequently diagnosed after 3 or more days. We used data from multiple sources, including demographic, clinical, treatment, laboratory, and vaccination information from a national network of hemodialysis clinics, socioeconomic information from the Census Bureau, and county-level COVID-19 infection and mortality information from state and local health agencies. We created prediction models and evaluated their performances on a rolling basis to investigate the evolution of prediction power and risk factors. Result: From April 2020 to August 2020, our machine learning model achieved an area under the receiver operating characteristic curve (AUROC) of 0.75, an improvement of over 0.07 from a previously developed machine learning model published by Kidney360 in 2021. As the pandemic evolved, the prediction performance deteriorated and fluctuated more, with the lowest AUROC of 0.6 in December 2021 and January 2022. Over the whole study period, that is, from April 2020 to February 2022, fixing the false-positive rate at 20%, our model was able to detect 40% of the positive patients. We found that features derived from local infection information reported by the Centers for Disease Control and Prevention (CDC) were the most important predictors, and vaccination status was a useful predictor as well. Whether or not a patient lives in a nursing home was an effective predictor before vaccination, but became less predictive after vaccination. Conclusion: As found in our study, the dynamics of the prediction model are frequently changing as the pandemic evolves. County-level infection information and vaccination information are crucial for the success of early COVID-19 prediction models. Our results show that the proposed model can effectively identify SARS-CoV-2 infections during the incubation period. Prospective studies are warranted to explore the application of such prediction models in daily clinical practice.

Diagnosis of cardiovascular disease in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) are at high risk of cardiovascular disease (CVD) and cardiovascular death. Identifying and monitoring cardiovascular complications and hypertension is important for managing patients with CKD or kidney failure and transplant recipients. Biomarkers of myocardial ischaemia, such as troponins and electrocardiography (ECG), have limited utility for diagnosing cardiac ischaemia in patients with advanced CKD. Dobutamine stress echocardiography, myocardial perfusion scintigraphy and dipyridamole stress testing can be used to detect coronary disease in these patients. Left ventricular hypertrophy and left ventricular dysfunction can be detected and monitored using various techniques with differing complexity and cost, including ECG, echocardiography, nuclear magnetic resonance, CT and myocardial scintigraphy. Atrial fibrillation and other major arrhythmias are common in all stages of CKD, and ambulatory heart rhythm monitoring enables precise time profiling of these disorders. Screening for cerebrovascular disease is only indicated in asymptomatic patients with autosomal dominant polycystic kidney disease. Standardized blood pressure is recommended for hypertension diagnosis and treatment monitoring and can be complemented by ambulatory blood pressure monitoring. Judicious use of these diagnostic techniques may assist clinicians in detecting the whole range of cardiovascular alterations in patients with CKD and enable timely treatment of CVD in this high-risk population.

Bisphenol A and Bisphenol S in Hemodialyzers.

Bisphenol A (BPA)-based materials are used in the manufacturing of hemodialyzers, including their polycarbonate (PC) housings and polysulfone (PS) membranes. As concerns for BPA's adverse health effects rise, the regulation on BPA exposure is becoming more rigorous. Therefore, BPA alternatives, such as Bisphenol S (BPS), are increasingly used. It is important to understand the patient risk of BPA and BPS exposure through dialyzer use during hemodialysis. Here, we report the bisphenol levels in extractables and leachables obtained from eight dialyzers currently on the market, including high-flux and medium cut-off membranes. A targeted liquid chromatography-mass spectrometry strategy utilizing stable isotope-labeled internal standards provided reliable data for quantitation with the standard addition method. BPA ranging from 0.43 to 32.82 µg/device and BPS ranging from 0.02 to 2.51 µg/device were detected in dialyzers made with BPA- and BPS-containing materials, except for the novel FX CorAL 120 dialyzer. BPA and BPS were also not detected in bloodline controls and cellulose-based membranes. Based on the currently established tolerable intake (6 µg/kg/day), the resulting margin of safety indicates that adverse effects are unlikely to occur in hemodialysis patients exposed to BPA and BPS quantified herein. With increasing availability of new data and information about the toxicity of BPA and BPS, the patient safety limits of BPA and BPS in those dialyzers may need a re-evaluation in the future.

Interactions between intradialytic central venous oxygen saturation, relative blood volume, and all-cause mortality in maintenance hemodialysis patients.

INTRODUCTION: In maintenance hemodialysis (HD) patients, low central venous oxygen saturation (ScvO2 ) and small decline in relative blood volume (RBV) have been associated with adverse outcomes. Here we explore the joint association between ScvO2 and RBV change in relation to all-cause mortality. METHODS: We conducted a retrospective study in maintenance HD patients with central venous catheters as vascular access. During a 6-month baseline period, Crit-Line (Fresenius Medical Care, Waltham, MA) was used to measure continuously intradialytic ScvO2 and hematocrit-based RBV. We defined four groups per median change of RBV and median ScvO2 . Patients with ScvO2 above median and RBV change below median were defined as reference. Follow-up period was 3 years. We constructed Cox proportional hazards model with adjustment for age, diabetes, and dialysis vintage to assess the association between ScvO2 and RBV and all-cause mortality during follow-up. FINDINGS: Baseline comprised 5231 dialysis sessions in 216 patients. The median RBV change was -5.5% and median ScvO2 was 58.8%. During follow-up, 44 patients (20.4%) died. In the adjusted model, all-cause mortality was highest in patients with ScvO2 below median and RBV change above median (HR 6.32; 95% confidence interval [CI] 1.37-29.06), followed by patients with ScvO2 below median and RBV change below median (HR 5.04; 95% CI 1.14-22.35), and ScvO2 above median and RBV change above median (HR 4.52; 95% CI 0.95-21.36). DISCUSSION: Concurrent combined monitoring of intradialytic ScvO2 and RBV change may provide additional insights into a patient's circulatory status. Patients with low ScvO2 and small changes in RBV may represent a specifically vulnerable group of patients at particularly high risk for adverse outcomes, possibly related to poor cardiac reserve and fluid overload.

Cardiovascular complications in chronic kidney disease: a review from the European Renal and Cardiovascular Medicine Working Group of the European Renal Association.

Chronic kidney disease (CKD) is classified into five stages with kidney failure being the most severe stage (stage G5). CKD conveys a high risk for coronary artery disease, heart failure, arrhythmias, and sudden cardiac death. Cardiovascular complications are the most common causes of death in patients with kidney failure (stage G5) who are maintained on regular dialysis treatment. Because of the high death rate attributable to cardiovascular (CV) disease, most patients with progressive CKD die before reaching kidney failure. Classical risk factors implicated in CV disease are involved in the early stages of CKD. In intermediate and late stages, non-traditional risk factors, including iso-osmotic and non-osmotic sodium retention, volume expansion, anaemia, inflammation, malnutrition, sympathetic overactivity, mineral bone disorders, accumulation of a class of endogenous compounds called 'uremic toxins', and a variety of hormonal disorders are the main factors that accelerate the progression of CV disease in these patients. Arterial disease in CKD patients is characterized by an almost unique propensity to calcification and vascular stiffness. Left ventricular hypertrophy, a major risk factor for heart failure, occurs early in CKD and reaches a prevalence of 70-80% in patients with kidney failure. Recent clinical trials have shown the potential benefits of hypoxia-inducible factor prolyl hydroxylase inhibitors, especially as an oral agent in CKD patients. Likewise, the value of proactively administered intravenous iron for safely treating anaemia in dialysis patients has been shown. Sodium/glucose cotransporter-2 inhibitors are now fully emerged as a class of drugs that substantially reduces the risk for CV complications in patients who are already being treated with adequate doses of inhibitors of the renin-angiotensin system. Concerted efforts are being made by major scientific societies to advance basic and clinical research on CV disease in patients with CKD, a research area that remains insufficiently explored.

Inclement Weather and Risk of Missing Scheduled Hemodialysis Appointments among Patients with Kidney Failure.

BACKGROUND: Nonadherence to hemodialysis appointments could potentially result in health complications that can influence morbidity and mortality. We examined the association between different types of inclement weather and hemodialysis appointment adherence. METHODS: We analyzed health records of 60,135 patients with kidney failure who received in-center hemodialysis treatment at Fresenius Kidney Care clinics across the Northeastern US counties during 2001-2019. County-level daily meteorological data on rainfall, hurricane and tropical storm events, snowfall, snow depth, and wind speed were extracted using National Oceanic and Atmosphere Agency data sources. A time-stratified case-crossover study design with conditional Poisson regression was used to estimate the effect of inclement weather exposures within the Northeastern US region. We applied a distributed lag nonlinear model framework to evaluate the delayed effect of inclement weather for up to 1 week. RESULTS: We observed positive associations between inclement weather and missed appointment (rainfall, hurricane and tropical storm, snowfall, snow depth, and wind advisory) when compared with noninclement weather days. The risk of missed appointments was most pronounced during the day of inclement weather (lag 0) for rainfall (incidence rate ratio [RR], 1.03 per 10-mm rainfall; 95% confidence interval [CI], 1.02 to 1.03) and snowfall (RR, 1.02; 95% CI, 1.01 to 1.02). Over 7 days (lag 0-6), hurricane and tropical storm exposures were associated with a 55% higher risk of missed appointments (RR, 1.55; 95% CI, 1.22 to 1.98). Similarly, 7-day cumulative exposure to sustained wind advisories was associated with 29% higher risk (RR, 1.29; 95% CI, 1.25 to 1.31), while wind gusts advisories showed a 34% higher risk (RR, 1.34; 95% CI, 1.29 to 1.39) of missed appointment. CONCLUSIONS: Inclement weather was associated with higher risk of missed hemodialysis appointments within the Northeastern United States. Furthermore, the association between inclement weather and missed hemodialysis appointments persisted for several days, depending on the inclement weather type.

Real-time prediction of intradialytic hypotension using machine learning and cloud computing infrastructure.

BACKGROUND: In maintenance hemodialysis patients, intradialytic hypotension (IDH) is a frequent complication that has been associated with poor clinical outcomes. Prediction of IDH may facilitate timely interventions and eventually reduce IDH rates. METHODS: We developed a machine learning model to predict IDH in in-center hemodialysis patients 15-75 min in advance. IDH was defined as systolic blood pressure (SBP) <90 mmHg. Demographic, clinical, treatment-related and laboratory data were retrieved from electronic health records and merged with intradialytic machine data that were sent in real-time to the cloud. For model development, dialysis sessions were randomly split into training (80%) and testing (20%) sets. The area under the receiver operating characteristic curve (AUROC) was used as a measure of the model's predictive performance. RESULTS: We utilized data from 693 patients who contributed 42 656 hemodialysis sessions and 355 693 intradialytic SBP measurements. IDH occurred in 16.2% of hemodialysis treatments. Our model predicted IDH 15-75 min in advance with an AUROC of 0.89. Top IDH predictors were the most recent intradialytic SBP and IDH rate, as well as mean nadir SBP of the previous 10 dialysis sessions. CONCLUSIONS: Real-time prediction of IDH during an ongoing hemodialysis session is feasible and has a clinically actionable predictive performance. If and to what degree this predictive information facilitates the timely deployment of preventive interventions and translates into lower IDH rates and improved patient outcomes warrants prospective studies.

Ultrafiltration Rate Levels in Hemodialysis Patients Associated with Weight-Specific Mortality Risks.

BACKGROUND: We hypothesized that the association of ultrafiltration rate with mortality in hemodialysis patients was differentially affected by weight and sex and sought to derive a sex- and weight-indexed ultrafiltration rate measure that captures the differential effects of these parameters on the association of ultrafiltration rate with mortality. METHODS: Data were analyzed from the US Fresenius Kidney Care (FKC) database for 1 year after patient entry into a FKC dialysis unit (baseline) and over 2 years of follow-up for patients receiving thrice-weekly in-center hemodialysis. To investigate the joint effect of baseline-year ultrafiltration rate and postdialysis weight on survival, we fit Cox proportional hazards models using bivariate tensor product spline functions and constructed contour plots of weight-specific mortality hazard ratios over the entire range of ultrafiltration rate values and postdialysis weights (W). RESULTS: In the studied 396,358 patients, the average ultrafiltration rate in ml/h was related to postdialysis weight (W) in kg: 3W+330. Ultrafiltration rates associated with 20% or 40% higher weight-specific mortality risk were 3W+500 and 3W+630 ml/h, respectively, and were 70 ml/h higher in men than in women. Nineteen percent or 7.5% of patients exceeded ultrafiltration rates associated with a 20% or 40% higher mortality risk, respectively. Low ultrafiltration rates were associated with subsequent weight loss. Ultrafiltration rates associated with a given mortality risk were lower in high-body weight older patients and higher in patients on dialysis for more than 3 years. CONCLUSIONS: Ultrafiltration rates associated with various levels of higher mortality risk depend on body weight, but not in a 1:1 ratio, and are different in men versus women, in high-body weight older patients, and in high-vintage patients.

The Impact of a Wearable Activity Tracker and Structured Feedback Program on Physical Activity in Hemodialysis Patients: The Step4Life Pilot Randomized Controlled Trial.

RATIONALE & OBJECTIVE: People with end-stage kidney disease (ESKD) have very low physical activity, and the degree of inactivity is strongly associated with morbidity and mortality. We assessed the feasibility and effectiveness of a 12-week intervention coupling a wearable activity tracker (FitBit) and structured feedback coaching versus wearable activity tracker alone on changes in physical activity in hemodialysis patients. STUDY DESIGN: Randomized controlled trial. SETTING & PARTICIPANTS: 55 participants with ESKD receiving hemodialysis who were able to walk with or without assistive devices recruited from a single academic hemodialysis unit between January 2019 and April 2020. INTERVENTIONS: All participants wore a Fitbit Charge 2 tracker for a minimum of 12 weeks. Participants were randomly assigned 1:1 to a wearable activity tracker plus a structured feedback intervention versus the wearable activity tracker alone. The structured feedback group was counseled weekly on steps achieved after randomization. OUTCOME: The outcome was step count, and the main parameter of interest was the absolute change in daily step count, averaged per week, from baseline to completion of 12 weeks intervention. In the intention-to-treat analysis, mixed-effect linear regression analysis was used to evaluate change in daily step count from baseline to 12-weeks in both arms. RESULTS: Out of 55 participants, 46 participants completed the 12-week intervention (23 per arm). The mean age was 62 (± 14 SD) years; 44% were Black, and 36% were Hispanic. At baseline, step count (structured feedback intervention: 3,704 [1,594] vs wearable activity tracker alone: 3,808 [1,890]) and other participant characteristics were balanced between the arms. We observed a larger change in daily step count in the structured feedback arm at 12 weeks relative to use of the wearable activity tracker alone arm (Δ 920 [±580 SD] versus Δ 281 [±186 SD] steps; between-group difference Δ 639 [±538 SD] steps; P<0.05). LIMITATIONS: Single-center study and small sample size. CONCLUSION: This pilot randomized controlled trial demonstrated that structured feedback coupled with a wearable activity tracker led to a greater daily step count that was sustained over 12 weeks relative to a wearable activity tracker alone. Future studies are required to determine longer-term sustainability of the intervention and potential health benefits in hemodialysis patients. FUNDING: Grants from industry (Satellite Healthcare) and government (National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT05241171.

Hemodiafiltration: Technical and Medical Insights.

Despite the significant medical and technical improvements in the field of dialytic renal replacement modalities, morbidity and mortality are excessively high among patients with end-stage kidney disease, and most interventional studies yielded disappointing results. Hemodiafiltration, a dialysis method that was implemented in clinics many years ago and that combines the two main principles of hemodialysis and hemofiltration-diffusion and convection-has had a positive impact on mortality rates, especially when delivered in a high-volume mode as a surrogate for a high convective dose. The achievement of high substitution volumes during dialysis treatments does not only depend on patient characteristics but also on the dialyzer (membrane) and the adequately equipped hemodiafiltration machine. The present review article summarizes the technical aspects of online hemodiafiltration and discusses present and ongoing clinical studies with regards to hard clinical and patient-reported outcomes.