Krister Cromm

Background: High-volume hemodiafiltration (HDF) improves survival and attenuates decline in selected patient-reported outcome (PRO) domains versus high-flux hemodialysis (HD). Whether benefits differ across clinically relevant subgroups remains uncertain. Methods: We conducted a prespecified subgroup analysis of the multicenter CONVINCE randomized controlled trial comparing high-volume post-dilution HDF (≥23 L/session) with high-flux HD in adults receiving maintenance dialysis. Eight PROMIS domains were assessed quarterly over a median follow-up of 30 months. Linear mixed-effects models evaluated longitudinal PRO changes and treatment-by-subgroup interactions by prespecified baseline characteristics: age, sex, diabetes, cardiovascular disease, dialysis vintage, vascular access type, and residual urine volume. Joint-model sensitivity analyses of all eight longitudinal PROMIS trajectories and time to death assessed informative dropout due to death. Results: Of 1360 randomized participants, 1211 with baseline and follow-up PRO assessments were included. PRO treatment effects were broadly consistent across prespecified clinical subgroups, without evidence of clinically meaningful heterogeneity. Models adjusted for baseline sociodemographic and clinical characteristics showed nominal treatment-by-subgroup interactions for dialysis vintage and physical function (P = 0.03), age and pain interference (P = 0.02), and dialysis vintage and sleep disturbance (P = 0.04). Joint-model sensitivity analyses accounting for informative dropout due to mortality reproduced the first two interactions and identified nominal interactions for vascular access type and sleep disturbance (P = 0.03) and cardiovascular disease status and cognitive function (P = 0.05). Interactions were modest in magnitude, exploratory, unadjusted for multiple comparisons, and not consistently observed across related PROMIS domains. Conclusions: This prespecified exploratory subgroup analysis found no convincing evidence of clinically meaningful treatment-effect heterogeneity across baseline characteristics examined. Nominal interactions were unadjusted for multiple comparisons and should be regarded as hypothesis-generating. Findings should not guide selection or exclusion of patients for high-volume HDF based on patient-reported outcomes.

Hemodiafiltration (HDF) with online production of substitution fluid has emerged as KRT and is increasingly adopted worldwide. Recent randomized controlled trials, individual participant data meta-analyses, and large real-world studies have demonstrated that high-volume HDF improves clinical outcomes compared with conventional high-flux hemodialysis, including reduction in all-cause mortality and hospitalization. Importantly, these benefits appear dose dependent, with achieved convective volume serving as a modifiable treatment target. Beyond survival, data suggest advantages in patient-reported outcomes and evidence for cost-effectiveness. This review provides a practical overview of contemporary HDF delivery, focusing on the prescription variables that determine treatment performance, including vascular access, blood flow rate, filtration fraction, treatment time, dialyzer characteristics, and machine technology. Current evidence suggests that high-volume postdilution HDF can be achieved safely and reproducibly in routine clinical practice using standard thrice-weekly treatment schedules and contemporary dialysis platforms. Monitoring should extend beyond conventional small-solute clearance metrics to include indicators of middle-molecule removal and patient-centered outcomes. Future developments are expected to move HDF from a uniform prescription strategy toward a more individualized approach. Emerging data support refinement of convection-volume targets according to patient characteristics and treatment response, while incorporation of patient-reported outcomes and predictive models may facilitate precision-based therapy. Advances in automation, digital monitoring, biosensors, and artificial intelligence are most likely to further optimize treatment delivery and personalization. Although implementation requires investment in infrastructure, training, and quality assurance, growing evidence suggests that these costs may be offset by improved clinical outcomes, reduced health care utilization, and enhanced sustainability. Collectively, current evidence supports high-volume HDF as among the most effective dialysis modalities currently available, and it is likely to become the global standard for KRT.

An abstract is unavailable. This article is available as a PDF only.

Key Points: Coverage of patient characteristics in existing trials of hemodiafiltration versus hemodialysis seems to be broad but incomplete. Randomized trials of hemodiafiltration versus hemodialysis have been primarily limited to Europe. Inconsistencies between trials and registries support further studies using real-world data to explore applicability of existing evidence. Background: Selection criteria in randomized trials (randomized controlled trials [RCTs]) can lead to differences in key characteristics between trial participants and real-life populations. We evaluated reporting of population characteristics in existing RCTs of hemodiafiltration (HDF) and in real-life populations included in kidney registries to descriptively identify key differences. Methods: We used systematic review methodology to identify existing RCTs of HDF versus hemodialysis (1966 to May 2024). We also searched the Fresenius Quantitative Market Analysis team registry database (2024 update) for existing registries from Europe, the Asia-Pacific region, and America including populations on HDF. Patient characteristics from RCTs and registries were extracted, summarized, and compared descriptively. Results: Eleven RCTs ( N =5108) and eight registries ( N =1,147,167) were identified. There were no RCTs in the United States and only two small RCTs from Australia ( N =124) and Brazil ( N =195). Most trials were from Europe. Key characteristics consistently reported in both RCTs and registries were only age, sex, diabetes, cardiovascular disease, vascular access type, and dialysis vintage. There was moderate to high heterogeneity for these patient characteristics in RCTs, indicating enrollment of a broad array of people. The proportion of people with diabetes was 26% in RCTs and 43% in registries. The prevalence of arteriovenous fistulas/graft was 90% in RCTs and 70% in registries. Conclusions: There was a broad but incomplete array of patient characteristics in existing RCTs and real-world registries of HDF versus hemodialysis. Data were primarily limited to Europe and only a core set of demographic and clinical variables. Apart for age, sex, diabetes, cardiovascular disease, vascular access type, and dialysis vintage, other patient and treatment relevant characteristics were erratically or not at all reported in RCTs as well as in real-world registries. With potential differences in patient populations, we support the need for studies examining HDF in real-world settings, e.g ., with target emulation trials.

Key Points: Health-related quality of life in dialysis depends on many nonclinical factors. Psychosocial determinants contribute to explaining variance in health-related quality-of-life domains better than demographic and medical variables alone. In comparison with past small-scale studies, self-efficacy showed significant associations with all aspects of health-related quality of life. Background: We investigated whether psychosocial determinants self-efficacy and social support are associated with health-related quality of life in patients on hemodialysis enrolled in the CONVINCE trial. Methods: We used baseline data from the cohort of patients involved in the CONVINCE randomized trial of hemodiafiltration versus hemodialysis. Measures included age, sex, relationship status, children, housing, education, employment, comorbidities, dialysis schedules, time of first dialysis, residual kidney function, general self-efficacy and social support scores, and Patient-Reported Outcomes Measurement Information System measurements for health-related quality of life. Associations were analyzed using hierarchical regression. Results: One thousand three hundred sixty patients from the CONVINCE trial were the cohort of interest. The mean age was 62±13.5 years (range, 20–92), and 66.9% were male. Self-efficacy was a significant predictor for all health-related quality-of-life domains: depression (β=−0.36, P < 0.001), anxiety (β=−0.35, P < 0.001), social participation (β=0.32, P < 0.001), cognition (β=0.29, P < 0.001), fatigue (β=−0.29, P < 0.001), physical function (β=0.27, P < 0.001), sleep disturbance (β=−0.23, P < 0.001), pain interference (β=0.21, P < 0.001), pain intensity (β=−0.17, P < 0.001), interdialytic symptoms (β=−0.14, P = 0.002), and intradialytic symptoms (β=−0.14, P = 0.002). Social support was a significant predictor for cognition (β=0.21, P < 0.001), sleep disturbance (β=−0.11, P = 0.017), and intradialytic symptoms (β=−0.11, P = 0.02). Conclusions: Higher general self-efficacy scale scores are associated with improvements in cognition, depression, anxiety, social participation, fatigue, physical function, sleep disturbance, pain interference, interdialytic symptoms, pain intensity, and intradialytic symptoms. Associations for self-efficacy are larger than those for social support and stronger than previously reported. It is plausible that targeted psychosocial interventions may improve health outcomes in people on hemodialysis. Podcast: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/K360/2025_01_30_KID0000000599.mp3

Several studies have suggested that patients with kidney failure may benefit from high-dose hemodiafiltration as compared with standard hemodialysis. However, given the limitations of the various published studies, additional data are needed. We conducted a pragmatic, multinational, randomized, controlled trial involving patients with kidney failure who had received high-flux hemodialysis for at least 3 months. All the patients were deemed to be candidates for a convection volume of at least 23 liters per session (as required for high-dose hemodiafiltration) and were able to complete patient-reported outcome assessments. The patients were assigned to receive high-dose hemodiafiltration or continuation of conventional high-flux hemodialysis. The primary outcome was death from any cause. Key secondary outcomes were cause-specific death, a composite of fatal or nonfatal cardiovascular events, kidney transplantation, and recurrent all-cause or infection-related hospitalizations. A total of 1360 patients underwent randomization: 683 to receive high-dose hemodiafiltration and 677 to receive high-flux hemodialysis. The median follow-up was 30 months (interquartile range, 27 to 38). The mean convection volume during the trial in the hemodiafiltration group was 25.3 liters per session. Death from any cause occurred in 118 patients (17.3%) in the hemodiafiltration group and in 148 patients (21.9%) in the hemodialysis group (hazard ratio, 0.77; 95% confidence interval, 0.65 to 0.93). In patients with kidney failure resulting in kidney-replacement therapy, the use of high-dose hemodiafiltration resulted in a lower risk of death from any cause than conventional high-flux hemodialysis. (Funded by the European Commission Research and Innovation; CONVINCE Dutch Trial Register number, NTR7138.).

Haemodiafiltration (HDF) provides a greater removal of larger solutes and protein-bound compounds than conventional high-flux haemodialysis (HD). There are indications that the patients receiving the highest convection volumes of HDF result in improved survival compared with HD. However, the comparative efficacy of HDF versus HD remains unproven. Here we provide a comparative account of the methodology and aims of ‘the comparison of high-dose HDF with high-flux HD’ (CONVINCE) study in the context of the totality of evidence and how this study will contribute to reaching a higher level of certainty regarding the comparative efficacy of HDF versus HD in people with end-stage kidney disease.