recent results from the national institutes of health ( nih ) frequent hemodialysis network ( fhn ) daily trial and the following rehabilitation , economics and everyday - dialysis outcome measurements ( freedom ) study have provided confirmation of the clinical and quality of life ( qol ) benefits of short daily hemodialysis ( sdhd ) when compared to conventional thrice weekly in - center hemodialysis ( chd ) .
the fhn study was conducted in - center ; however , sdhd in the usa is more commonly performed as a home therapy and is not offered as a standard treatment modality in most dialysis clinics .
although it has been nearly 50 years since the early pioneers such as belding scribner and stanley shaldon began dialyzing patients in their homes , peaking at 40% of all us dialysis patients in 1973 , the popularity of home hemodialysis ( hd ) has been limited in the usa for a number of reasons , including lack of suitable equipment and increased cost .
the last few years , however , have seen a revival in home hd , resulting in renewed interest in the various forms of more frequent therapy , including sdhd .
the revival of home dialysis was led in the mid 1990s by robert uldall , andreas pierratos and others in canada , gradually spreading throughout the usa .
this re - emergence has been made possible by recent advances in technology , including portable and more user - friendly machines designed specifically for use in the home environment . in 2005 , the fda cleared the first hd machine for home use in the usa , the nxstage system one. fda clearance was based on an open - label , prospective , two - treatment two - period crossover study on 32 patients to compare sdhd performed in - center ( prescribed six times / week ) versus sdhd performed at home .
the study was conducted at six centers in the usa under an investigational device exemption .
this study showed sdhd was delivered as efficiently in the home environment as in - center , with 98.5% of treatments performed successfully in - center versus 97.3% at home .
notably , the composite rate of intra - dialytic and inter - dialytic adverse events was significantly higher during the in - center phase when compared with the home phase ( 5.3 versus 2.1 adverse events/100 treatments ; p = 0.007 ) , suggesting hd therapy is at least as safe at home as in - center .
when comparing clinical parameters from the period immediately preceding the study when patients were treated with conventional thrice weekly center hd , home sdhd was associated with reductions in blood pressure , antihypertensive medications and interdialytic weight gain . since the clearance of the nxstage system one in the usa , the number of patients now performing home dialysis is estimated to be 5000 , with the majority of these patients performing sdhd .
although this represents a considerable increase over the past 5 years , it is still only 1% of the total end - stage renal disease ( esrd ) population .
sdhd offers the promise of improved clinical outcomes in patients with kidney failure , and given the positive results recently released from both the fhn and freedom studies outlined below , sdhd has the potential to become a more viable and popular choice amongst many esrd patients .
results recently published from the fhn daily trial , funded by the nih , showed that in - center sdhd ( prescribed six times / week ) , provided significant benefits in both composite co - primary outcomes of death or 12-month change in left ventricular mass ( lvm ) and death or 12-month change in the rand-36 physical health composite ( phc ) score .
specifically , the fhn daily trial showed patients randomized to sdhd reduced their lvm by 16.3  35.3 g ( p < 0.001 ) and improved their phc score by 3.3  8.9 points ( p = 0.004 ) , after 12 months .
however , patients on sdhd were more likely to undergo interventions related to vascular access , a result which will require further elucidation with the ongoing analysis of the trial
. the fhn trial will be a tremendous source of data to further dissect the advantages seen with daily therapy in the coming years .
the freedom study is an ongoing prospective cohort study investigating the clinical and economic benefits of sdhd .
the objectives of the freedom study are to compare a cohort of patients starting sdhd using the nxstage system one to a matched cohort of patients receiving chd for all - cause hospitalizations and non - treatment - related medical expenditures .
using a 10-to-1 ratio , totaling 5000 patients , the matched thrice weekly in - center hd cohort will be obtained from the us renal data system ( usrds ) database .
in addition , changes in qol measures , urea kinetics , management of anemia , bone and mineral metabolism , nutrition , vascular access interventions and use of medications will be examined .
the freedom study will involve up to 70 clinical sites and 500 participants , with a minimum 1-year follow - up .
study participants complete qol surveys at the time of study enrollment , at 4 and 12 months and every 6 months thereafter .
interim data recently released from the freedom study has shown that sdhd , performed in the home environment , is associated with significant improvements in several important clinical and qol measures when compared to conventional thrice weekly in - center hd .
interim results from the freedom study investigating the effect of sdhd on depressive symptoms were recently published .
depressive symptoms were examined in 248 participants at enrollment and at 4 and 12 months by administering the validated beck depression inventory ( bdi)-ii survey .
the study protocol requires that the site investigator be notified immediately of a bdi score > 10 , with mild and moderate to severe depressive symptoms defined as bdi scores of 1115 and > 15 , respectively . in summary ,
sdhd was associated with a significant improvement in mean bdi score over 12 months [ 11.2 , 95% confidence interval ( ci ) 9.612.9 , versus 7.8 ( 95% ci 6.59.1 ) ; p < 0.001 ] , in the per - protocol ( pp ) cohort .
similar results were found in the intent - to - treat ( itt ) cohort . for participants with moderate to severe depressive symptoms , the bdi scores almost halved over 12 months [ 24.4 ( 95% ci 19.429.4 ) versus 12.6 ( 95% ci 8.017.2 ) ; p < 0.001 ] .
it should be noted that a bdi score > 15 previously has been shown to be highly predictive of a diagnosis of clinical depression .
the percentage of participants with depressive symptoms ( bdi score > 10 ) significantly decreased during 12 months ( 41 versus 27% ; p < 0.03 ) . similarly in the fhn study , patients participating in the daily arm did show a trend toward improvement after 12 months when compared to baseline ( 12.6  8.7 versus 10.4  8.5 , p = 0.1 ) .
although this trend was not statistically significant , one might speculate that undergoing daily dialysis therapy at home may contribute to this improvement .
considering the practical feasibility of daily dialysis both from a logistical and a patient comfort perspective , one might hypothesize that the home setting may further enhance the benefits of sdhd experienced in - center .
the long - term effect of sdhd on post - dialysis recovery time was also assessed in the freedom study by administering the following previously validated question :  how long does it take you to recover from a dialysis session and resume your normal , usual activities?   interim results were recently published   and confirmed that sdhd is associated with a significant decrease in post - dialysis recovery time [ 476 min ( 95% ci 359594 ) versus 63 min ( 95% ci 3295 ) ; p < 0.001 ] .
the percentage of participants experiencing prolonged post - dialysis recovery time ( > 60 min ) also significantly decreased over the 12-month period ( 81 versus 35% ; p < 0.001 ) .
the fhn daily trial showed significant improvements in control of hyperphosphatemia for patients on sdhd .
a significant reduction in mean serum phosphate was also reported in an interim report from the freedom study , along with significant reductions in the calcium  phosphate product , serum creatinine , serum potassium and a trend toward a reduction in blood urea nitrogen .
both the fhn daily trial and an interim analysis from the freedom study showed no change in serum albumin levels .
well - known uremic symptoms , including restless legs symptoms ( rls ) and poor sleep quality are common in the hd population .
poor sleep quality and rls have both been linked to increased risk of death for these patients [ 9 , 10 ] .
a recent interim report from the freedom study demonstrated initiation of sdhd at home is associated with significant improvement in rls and sleep disturbances .
results from 235 patients found 40% suffered from rls at baseline , which was associated with poorer sleep quality and respiratory disturbances . among patients with rls , the mean irls ( international restless legs severity scale ) score improved significantly at month 12 , after adjustment for use of rls - related medications ( 18 versus 11 , p < 0.0001 ) . among patients with moderate - to - severe rls ( irls score 15 )
, there was an even greater improvement in the irls score ( 23 versus 13 , p < 0.001 ) . over the 12-month period , there was decline in the percentage of patients reporting rls ( 35 versus 26% , p = 0.05 ) and those reporting moderate - to - severe restless legs symptoms ( 59 versus 43% , p = 0.06 ) .
there was a similar and sustained improvement in several scales of the medical outcomes study sleep survey over 12 months , after adjustment for presence of rls and use of anxiolytics and hypnotics .
recent results from both the fhn daily trial and freedom study have shown that sdhd , performed either in - center or at home , is associated with several important clinical and qol benefits when compared to conventional thrice weekly hd .
the improvements in left ventricular mass , control of hypertension and improvement in hyperphosphatemia demonstrated in the fhn trial , in conjunction with the positive interim findings from the freedom study , including improvements in depressive symptoms , post - dialysis fatigue , various laboratory parameters , restless leg syndrome and sleep disorders , confirm the anecdotal benefits of sdhd seen and reported by many practicing nephrologists and their patients . until now
, a complex variety of reasons has hindered the more widespread use of sdhd in the usa and globally .
however , the results of these studies may provide a new impetus for esrd patients and nephrologists to reconsider the paradigm of thrice weekly center hd as the  default therapy. such a paradigm shift will likely increase the possibility for improved clinical outcomes and overall patient care for those affected by esrd .
 thrice weekly in - center hemodialysis is the standard of care for dialysis patients with end - stage renal disease ( esrd ) . however , there is ongoing debate as to whether more frequent hemodialysis , with its readier management of both toxin and fluid removal , benefits patients . 
 new evidence from recent studies , both in center dialysis and in home haemodialysis patients , adds further confirmation of improved cardiovascular outcome and quality of life in patients undergoing short daily hemodialysis . 
 a paradigm shift in esrd care delivery may be facilitated due to new technology enabling daily therapy at home . 