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3.1. Impact on HDF for Survival
The patient survival outcomes associated with HDF have been subject to extensive review [5]. The most recent investigations have focused on the survival effects of high CV achieved through post-dilution online HDF in European settings. Randomized controlled trials (RCTs), including the Dutch CONTRAST trial [18], comparing post-dilution HDF versus low flux HD, and the Turkish study [19], ESHOL study [20], and French study [21], which all compare post-dilution HDF versus high-flux HD, have collectively reported that augmenting CV with HDF (with CV values of 22 L [18], 17.2 L [19], 20.7 L [20], and 22.9–23.9 L [21] in each respective study) demonstrates a proportionate enhancement in patient survival.
However, it is essential to note that these RCTs did not explicitly establish CV as a designated treatment objective and did not definitively account for the potential presence of confounding factors. In cases where a higher CV might have been attained, such as in individuals characterized as “healthy” with fewer comorbidities, the presence of native vascular access, and higher blood flow, the risk of mortality was observed to be lower. It is worth acknowledging that these factors were not systematically controlled for in the study design.
Furthermore, the relatively low mean age of the study participants (53 years) and the absence of comprehensive information regarding the selection process and participating centers raised questions about the generalizability of the findings to the broader dialysis population. Consequently, it remained uncertain whether the procedure was universally applicable to all dialysis patients [22]. The theoretical significance of increased solute removal as a determinant of improved life expectancy also warranted further clarification, as no specific upper limit for CV had been proposed.
Conversely, an observational study conducted using Euro-DOPPS 4–5 failed to demonstrate a discernible advantage of HDF [23]. Likewise, an RCT in Australia, comparing post-dilution HDF with a CV of 24.7 L to high-flux HD, did not reveal any substantial survival benefit or improvements in neurological symptoms [24]. It is plausible that the prolonged dialysis duration (5 h) and the favorable survival rates (1-year survival exceeding 90%) in this particular study may have contributed to the absence of differential outcomes.
To address the limitations observed in prior HDF studies, two extensive RCTs were conducted in Europe [22]: the CONVINCE study (Comparison of high-dose HDF with high-flux HD) and the H4RT (High-volume HDF versus High-flux HD Registry Trial). These trials encompassed not only assessments of life expectancy but also explored outcomes related to hospitalization, quality of life, and cost-effectiveness.
In the primary analysis of CONVINCE conducted in 2023, a notable 33% reduction in all-cause mortality over a span of 3 years was reported in the high-dose HDF group (CV > 23 L) comprising 683 patients in comparison to the high-flux HD group with 677 patients. Subsequent sub-analyses highlighted specific benefits, particularly among patients without cardiovascular disease (CVD) or diabetes [25].
Nevertheless, it is essential to acknowledge that this RCT coincided with the COVID-19 pandemic, which could potentially have impacted hospitalization rates and other variables. Ongoing investigations and further analyses are slated for the future to gain a more comprehensive understanding of these findings [26].
Pre-dilution HDF in Japan is specifically tailored for αMG removal, and Sakurai et al. have reported an impressively high αMG removal rate of 35–40% or even higher, particularly for managing conditions such as bone–joint pain and restless leg syndrome [27]. The targeted removal of αMG holds significant clinical relevance, and the current objective is to establish treatment parameters that maximize αMG removal while minimizing albumin leakage. It is worth noting that a slight increase in the removal rate within the high removal rate range can lead to an excessive amount of removal [28].
Furthermore, in accordance with data analysis conducted by the Japanese Renal Data Registry (JRDR) of the Japanese Society of Dialysis Therapy (JSDT), it was observed that the survival rate improved in pre-diluted HDF with a substitution volume of 40 L or more. Notably, the substitution volume that contributed most significantly to enhanced survival was found to be 50.5 L, implying a U-shaped relationship between survival and substitution volume [29]. Additionally, Sakurai et al. demonstrated that highly efficient HDF led to the release of the platelet surface marker CD62P, suggesting increased stress on blood cell components [30].
Based on these findings, it is recommended that pre-dilution HDF in Japan be administered under conditions characterized by a blood flow rate within the range of 250–300 mL/min and a substitution volume of 200–240 mL/min (equivalent to 48–58 L).
