To date, no randomized controlled trial has demonstrated a significant survival advantage for IHHD over conventional hemodialysis (CHD). Survival data from randomized trials on this subject come from the Frequent Hemodialysis Network (FHN) studies. The FHN daily study [2]found a significant difference in the primary composite endpoint of fewer deaths and less left ventricular hypertrophy (LVH) in the frequent hemodialysis group (center-based) compared with the conventional hemodialysis group. This study was then extended over a median period of 3,6 years (range 1,5 to 5,3 years) after randomization, with the observation of lower mortality and a relative risk (RR) of mortality for frequent hemodialysis versus conventional hemodialysis of 0,54 [3]. With regard to LNHD, the FHN nocturnal study [4]found no difference in terms of survival or reduction in LVH. These negative results were possibly linked to the high proportion of residual renal function (RRF) loss in the LNHD group (compared with an unusually high RRF in the CHD group) and, above all, to underpowering of the mortality study (low mortality in the CHD group, small number of patients, insufficient compliance with nocturnal treatment). The study was then extended to 5 years [5], with an increase in mortality observed in the LNHD group, but with an increase in the dialysis dose for a large number of patients in the CHD group, with more than 3 sessions per week and more than 27 hours of dialysis per week after the first 12 months, making any final interpretation difficult.

Other survival data on IHHD are derived from observational studies, with all the limitations inherent to these studies’ characteristics, but partly offset by the large number of studies showing a survival benefit of IHHD over CHD. In particular, LNHD was found to be beneficial in several studies, with a reduction in the RR of mortality [6][7][8]. In the case of SDHD, Blagg et al. found a reduction in mortality with an RR reduction of 0,39 in comparison with incident patients from the United States Renal Data System (USRDS) registry [9][10] Kjellstrand et al. observed a 2- to 3-fold increase in survival compared with a group of CHD patients [9]. Marshall et al. reviewed the Australian and New Zealand registries comparing CHD with different HHD modalities and found a nonsignificant survival advantage for IHHD (RR 0,56) versus CHD, while home CHD had the same mortality rate [11][12]. Rydell et al. carried out a cohort study with 152 incident patients receiving home hemodialysis (15 hours per week) at high flow, performed diurnally and nocturnally, compared with 608 patients on CHD and 456 on peritoneal dialysis (PD) over a mean duration of 10,4 years, and observed an increase in survival in the HHD group compared with the CHD and PD groups [13].

With regard to SDHD at low dialysate flow, the main study is that of Weinhandl et al., which is a prospective observational study comparing 1873 patients on SDHD with the NxStage™ monitor versus 9365 patients on CHD (3 times a week) over 3 years: they observed a 13% reduction in mortality (RR 0,87) with an RR of 0,92 for cardiovascular mortality and a more marked benefit on the diabetic and obese population. The SDHD group was younger and less comorbid, but this difference was offset by matching [14].

Finally, a 2018 Canadian meta-analysis included 23 studies comparing CHD with different IHHD techniques (home and center) and found lower mortality in IHHD compared with CHD (RR of LNHD = 0,46, RR of SDHD = 0,54) [15].

Lockridge et al. estimated the results of different dialysis techniques compared with renal transplantation to tailor dialysis prescriptions as closely as possible to patients’ needs ( Table II) [16].

Chronic hemodialysis patients are at high cardiovascular risk, with an excess risk of cardiovascular morbidity and mortality 10 to 30 times higher than in the general population. Controlling cardiovascular risk is therefore particularly important in this population.

Hypertension control is one of the particularly beneficial effects of IHHD, with a high level of evidence for both SDHD and LNHD. A significant reduction in blood pressure (BP) and a reduction in treatment were found in the FHN studies, as well as in the randomized ACTIVE and ALBERTA studies [17][18]. This beneficial effect was found in several other non-randomized studies [19][20][21][31], and notably in the European retrospective cohort study KIDHNEy involving 104 SDHD patients with the NxStage™ monitor followed over 6 months [22]. The improvement in BP control observed with IHHD is probably related to volume control and reduction in peripheral vascular resistance [19][23][24].

The reduction in LVH also benefits from a high level of evidence, with a significant drop in the FHN daily study and in the LNHD group of the randomized ALBERTA study [2][18]. No difference was found in the FHN nocturnal study, with the limitations cited above, or in the ACTIVE study [4][17]. Several observational studies have observed a decrease in LVH in both diurnal SDHD [19][21][25]and LNHD [18][26].

IHHD’s positive effect on increased phosphoremia control has also been observed. This effect has been observed in SDHD [2][27], extended hemodialysis [8][17], and especially LNHD [4][18][28], with discontinuation of phosphorus binders and sometimes the need for per-session phosphorus supplementation.

Another major aspect described with frequent hemodialysis is the reduction in the effect of per-session myocardial sideration of dialysis, resulting from segmental and global cardiac ischemic damage and leading to long-term cardiac dysfunction. This positive impact was found in the observational cross-sectional study by Jefferies et al. [29], who carried out per-session cardiac echocardiography in 4 groups of hemodialysis patients (CHD, frequent in-center hemodialysis, home SDHD, home LNHD) and found a reduction in segmental and global kinetic disorders in the frequent hemodialysis groups, associated with a fall in ultrafiltration levels and cardiac markers (BNP and troponin).

The final aspect is the observation of a reduction in cardiovascular hospitalizations with both LNHD [29][30]and SDHD [14][32].

One of HHD’s key advantages is its flexibility, giving patients the freedom to carry out their sessions according to the demands of their daily lives, dietary deviations, and leisure activities. HHD’s influence on quality of life has been evaluated in numerous studies [4][18][33][34][35], with a positive impact on the experience of the burden of kidney disease. In addition to an increase in quality of life, the FREEDOM study found a significant improvement at 1 year in the depression inventory after switching patients to home SDHD on NxStage™ [27]and a reduction in restless leg syndrome associated with an increase in sleep quality.

The other major aspect is fertility, which is greatly reduced in CHD. Few data have been published, but IHHD, in particular LNHD, seems to increase the chances of successfully carrying a pregnancy to term [36].

The increased risk of VA complications has been described in the FHN studies. Suri et al. reported the FHN cohort data, observing a 76% increase in the risk of VA complications with 55% thrombectomy and revision surgery. The risk of complications was higher for arteriovenous fistulas (AVFs). However, there was no difference in VA loss or the infection rate [36] [37]. Three VA-related deaths were described: one in each group of the FNH diurnal study and one in the LNHD group on gas embolism (presence of a central venous catheter (CVC)).

Weinhandl et al. found a nonsignificant increase in infectious mortality [14]but no direct causal relationship with an increase in VA infections.

The impact of HHD on the increase in VA complications remains controversial, with an increase observed in several observational studies [38][39]but not found in the randomized ALBERTA and ACTIVE studies [17][18]. Nor was any difference observed in Achinger et al.’s prospective study [40].

This heterogeneity of results is probably linked to various factors: firstly, the difference in VA used for HHD, whether AVF or CVC, and when using AVF, the practice of the buttonhole technique. The latter is associated with an increased risk of infection, with an RR of 3,18 compared with the cord technique in Muir et al.’s review [40]. The risk of infection can be reduced by the systematic use of mupirocin [42][43]: the application of this preventive measure, combined with optimal patient training and regular follow-up, is probably a second factor that may explain the discrepant results in terms of VA complications. Prevention remains essential, not only in terms of infection, but also in terms of AVF thrombosis and CVC dysfunction. A survey of 19 HHD centers in the USA revealed inadequate training of nurses and patients, which may increase the risk of infection [44].

Loss of RRF has been mainly described in LNHD. The FHN cohort study found a 67% loss of RRF in the LNHD group versus 36% in the CHD group (P = 0,06), but there was no difference in the FHN daily study, subject to a majority of anuric patients in the 2 groups (72% in the IHHD group, 60% in the CHD group) [45].

The mechanisms potentially involved in this loss of RRF are better volemic and osmotic control, better blood pressure control with lower BPs, and discontinuation of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) with significantly lower prescribing in IHHD [46].

Analysis of the FHN studies found an increase in caregiver burden in the LNHD group [47]. Walker et al.’s review of 24 studies found greater anxiety and apprehension among patients and caregivers, particularly in countries less accustomed to SDHD [48], suggesting once again that burnout could be prevented by optimizing patient training and follow-up.

The essential criteria for HHD are patient motivation and autonomy. Apart from the absence of these criteria, there are very few contraindications to HHD. Other barriers to IHHD include lack of compliance, cluttered and/or unhealthy housing, and VA difficulties. For the time being, dependent people cannot benefit from a home nurse, unlike PD patients in France.

The absence of a caregiver is theoretically a contraindication in France, since the presence of a third party during the dialysis session is mandatory by law, unlike in other countries. This obligation is regularly circumvented, with 95% of home hemodialysis patients declaring that their designated caregiver is not present during their dialysis session. Several nephrologists and patient associations have called for this obligation to be abolished, as it potentially deprives patients living alone of being placed on IHHD.