Abstract:
End-stage renal disease is associated with poor outcomes, including increased mortality, significant morbidity, and lower quality of life. In-center conventional hemodialysis, performed thrice-weekly for 3 to 5 hours, and peritoneal dialysis remain the most common forms of renal replacement therapy in the majority of the world. However, in recent years, with efforts to improve outcomes for patients with end-stage renal disease, there has been resurgence in interest for frequent hemodialysis with emerging evidence of benefits. This chapter examines the physiological rationale, established benefits and risks, prescription options, and practical aspects for frequent hemodialysis.
Keywords
extended hemodialysis, frequent hemodialysis, hemodialysis training, home hemodialysis, intensive hemodialysis, short-daily hemodialysis
Outline
Definition of Terms, 427
History of Frequent Hemodialysis, 427
Physiological Rationale, 428
Improved “Unphysiology” With Frequent Hemodialysis, 428
Improved Clearance of Small Water-Soluble Solutes, 428
Improved Clearance of Small Protein-Bound Solutes, 428
Improved Clearance of Middle Molecules, 429
Improved Fluid Status With Lower Ultrafiltration Rates, 429
Benefits and Risks: Review of the Current Evidence, 429
Clinical Indications, 432
Prescriptions for Frequent Hemodialysis, 432
Implementing A Frequent Hemodialysis Program, 434
Frequent Home Hemodialysis program, 434
In-center Daily Hemodialysis Program, 435
In-center Nocturnal Hemodialysis Program, 435
Economic Considerations, 435
Medication Dosing Considerations, 435
International Trends and Variation, 436
Overcoming Barriers in Uptake of Frequent Hemodialysis, 436
Frequent Hemodialysis in Children, 436
Future Directions, 436
End-stage renal disease (ESRD) is associated with poor outcomes including high mortality, significant morbidity, and lower quality of life (QoL). Facility-based conventional hemodialysis (HD), performed thrice-weekly for 3 to 5 hours, and peritoneal dialysis (PD) remain the most common forms of renal replacement therapy for the majority of patients worldwide. In recent years, with efforts to improve outcomes for patients with ESRD, there has been resurgence in interest for frequent HD with emerging evidence of benefits. This chapter examines the physiological rationale, established benefits and risks, prescription options, and practical aspects of frequent HD.
Definition of Terms
Several terms have been used to describe the various frequent HD regimens, including short-daily , nocturnal , quotidian , intensive , long , and alternative . Conventional HD is typically defined as three to four sessions per week lasting 3 to 5 hours each. As for frequent HD, three predominant regimens are commonly identified: short-daily, long, and long-frequent ( Box 27.1 ). These treatments may be performed either in a dialysis facility or at home. Short-daily HD consists of five or more sessions per week of short duration (2.5 to 3.5 hours). Long HD involves three to four weekly treatments of 6 to 8 hours. On the other hand, long-frequent HD combines both increased frequency (five or more weekly sessions) and longer duration (6 to 8 hours). Both long and long-frequent HD are usually performed at night while patients sleep.
| Short-Daily |
|
| Long |
|
| Long-Frequent |
|
History of Frequent Hemodialysis
HD was first described in 1960, in Seattle, when Scribner and colleagues developed the Teflon arteriovenous shunt. When HD was introduced, treatments were long and infrequent (12 to 18 hours every 10 to 15 days). Since the minimal dose of dialysis required to treat uremic symptoms was unknown, there was no standard session duration or frequency. With time, the frequency of dialysis was increased from every 10 to 15 days to twice then three times a week. Thrice-weekly HD then became the most widely recognized regimen, since it was believed that patients felt better with this schedule. However, as demand for in-center HD began to exceed its availability, home HD became a reality in the 1960s, credited to Shaldon. By the 1970s, a large proportion of patients were treated at home, usually at night, twice or three times a week. Concomitantly, in 1969, DePalma et al. published the first report of daily HD when they changed seven patients from 8 hours thrice-weekly to five times per week for 4 to hours with resulting improvement in blood pressure and urea clearance. In the 1970s, the development of hollow-fiber dialyzers led to a shortening of the length of dialysis sessions to the current 3.5 to 5 hours three times a week. However, the Tassin Center in France continued to perform long intermittent 8-hour thrice-weekly HD until now with excellent reported outcomes of blood pressure and survival. During the same period, availability of funding resulted in a rapid expansion of outpatient dialysis units and PD increased in use, thus leading to a rapid decline of home HD.
Subsequently, during the 1980s, short-daily HD programs were established in many European centers as rescue therapy after failure of conventional therapy. In 1994, slow, frequent nocturnal home HD was first reported by Dr. Robert Uldall in Toronto, Canada. He described results of six patients treated at home during sleep ≥6 nights per week using a central venous catheter (CVC). Ever since, there has been resurgence in the interest for longer and more frequent HD, as well as home HD, with considerable evidence continuing to support the benefits of intensive therapy.
Physiological Rationale
With progressive renal failure, uremia results from the accumulation of organic waste products normally excreted by healthy kidneys. Since many uremic compounds have yet to be identified, it is still unclear what exactly causes the uremic syndrome. Furthermore, some of these products may not be toxic. Nonetheless, three major groups of uremic solutes are described :
- 1)
small water-soluble products (molecular weight <500 Da)
- 2)
small protein-bound solutes (molecular weight <500 Da)
- 3)
middle molecules (molecular weight 500 to 60,000 Da)
The differences in molecular weight, availability in the plasma compartment, and water/lipid-solubility of these solutes dictates the efficiency of their removal with dialysis. Plasma availability is, in turn, influenced by the diffusion rate of these molecules across intercompartmental barriers (e.g., cell membrane) and protein-binding capacity.
Improved “Unphysiology” With Frequent Hemodialysis
Although healthy kidneys continuously excrete uremic compounds, conventional HD is delivered only thrice weekly for 3 to 5 hours. Hence, conventional HD results in wide fluctuations of solutes in a saw-tooth pattern, which has been characterized as the “unphysiology” of dialysis by Dr. Kjellstrand. Moreover, conventional HD results in a long 2-day interdialytic interval, a period of higher mortality, and cardiovascular events. Frequent HD results in smaller oscillations with lower time-averaged concentrations of these retention solutes due to longer treatment duration, increased dialysis frequency, and shorter interdialytic intervals. Thus clearance of uremic waste products is potentially increased with frequent HD regimens.
Improved Clearance of Small Water-Soluble Solutes
With small water-soluble solutes, removal rates are highest at the start of HD with subsequent exponentially decreasing rates during conventional HD since the blood-dialysate concentration gradient decreases with time. However, although only solutes in the plasma component are cleared with dialysis, most solutes also are distributed within intracellular and interstitial compartments. In fact, the concentrations of these small uremic compounds begin to rise immediately after conventional dialysis, known as a rebound . Even if many of these solutes easily diffuse across cellular membranes, movement from intracellular and interstitial spaces into the plasma compartment may take up to 60 to 120 minutes after a conventional HD session. Increased dialysis treatment time and frequency allow for greater intercompartmental solute diffusion. Thus rebound is decreased and overall solute clearance potentially increased.
Urea is the most widely recognized small water-soluble uremic solute with a molecular weight of 60 Da, and often is used as a measure of dialysis adequacy. Studies have demonstrated that short-daily HD can increase weekly urea clearances by 30% to 50%. By the same token, frequent nocturnal HD has been shown to approximately double weekly urea clearance compared with conventional therapy.
Improved Clearance of Small Protein-Bound Solutes
Kinetic patterns of protein-bound molecules differ from that of urea. Shift from intracellular to extracellular compartments are impeded by the degree of protein binding. With longer and/or more frequent treatment, clearance of these molecules is potentially higher with increased time for intercompartmental movement of solutes. However, studies evaluating protein-bound molecules clearance with extended or frequent HD have led to mixed results. In a study of 13 patients who underwent different dialysis regimens, extended HD (8 hours) was associated with a significant increase in removal of protein-bound uremic toxins. Conversely, in a crossover study, Basile et al. demonstrated no significant change in protein-bound solute clearance with prolonged HD, although small and middle molecule clearance was higher. More recently, an analysis of samples from the FHN (Frequent Hemodialysis Network) trial showed no significant reduction in the protein-bound uremic toxins p -cresol sulfate or indoxyl sulfate with increased treatment frequency. These conflicting results may be explained by the small sample size of some of these prior studies as well as the varying degree of protein-binding of some of these molecules. It should be noted that other poorly understood factors likely play a role in uremic solute concentration such as nonrenal clearance and changes in solute production.
Improved Clearance of Middle Molecules
Many middle molecules have been shown to be clinically important uremic toxins.
Longer dialysis treatment time would potentially allow for more time for middle molecule movement from intracellular to extracellular compartment and thus increase clearance of these molecules. β2-microglobulin (B2M), implicated in the pathogenesis of dialysis amyloidosis, has been the most extensively studied. Higher serum B2M levels have equally been shown to be associated with mortality. Several studies have demonstrated that longer dialysis increases B2M removal. Similarly, although of small molecular size, phosphate also is considered widely to behave like a middle molecule given its mainly intracellular distribution with slow diffusion across the cell membrane. Increased frequency and dialysis duration have been reported to have a positive impact on dialysis phosphate removal.
Improved Fluid Status With Lower Ultrafiltration Rates
Fluid overload is common in patients on thrice-weekly HD and is associated with higher mortality and morbidity. To achieve euvolemia, rapid fluid removal with high ultrafiltration (UF) rates often is used in conventional HD. However, this may cause intradialytic hypotension, leading to myocardial, mesenteric, or cerebral ischemia; nausea; cramping; and vascular access complications. Moreover, episodes of intradialytic hypotension may lead to premature discontinuation of dialysis with resulting failure to reach target weight, thus potentially worsening hypertension and left ventricular hypertrophy (LVH). Indeed, it has been shown that UF rates of >10 mL/kg/h are associated with higher mortality and worse cardiovascular outcomes. With increased frequency and/or longer treatment duration, UF rates can be reduced with more time allowed for vascular refill. As such, intradialytic symptoms may be minimized, and this may potentially improve fluid status, and consequently, cardiovascular outcomes. Indeed, frequent HD regimens are associated with lower UF rates in addition to less dialysis-induced myocardial stunning compared with conventional HD.
Benefits and Risks: Review of the Current Evidence
In recent years, there has been growing research investment and continued demonstrated advantages with intensive HD, both short-daily and long nocturnal. In this section, we review the evidence surrounding the clinical benefits with frequent HD and also elaborate on the potential risks with this therapy.
Clinical Benefits
Survival
To our knowledge, there has been no adequately powered randomized controlled trial (RCT) comparing survival between intensive and conventional HD. Although several observational studies have demonstrated excellent patient survival with frequent HD, interpretation of results is limited by potential selection bias, residual confounding, different definitions of frequent HD, and varying practice patterns.
Many studies have shown better outcomes with longer treatment length. In a study that included HD patients from seven countries in the DOPPS (Dialysis Outcomes and Practice Patterns Study), treatment duration >240 minutes was associated with a significant 19% lower risk for mortality after adjustment. Similarly, in a recent retrospective study of a large multicenter US cohort, Rivara et al. demonstrated a 33% lower adjusted mortality risk with extended-hours HD compared with conventional regimens.
There also have been excellent survival reports with intensive nocturnal HD . In a cohort of 247 Canadian nocturnal HD patients, patient survival was 95% and 80% at 1 and 5 years, respectively. Comparably, in an Australian cohort of 286 home nocturnal patients, overall survival was 98% and 83% at 1 and 5 years. For better comparison with conventional HD, Nesrallah et al. matched intensive home HD patients in the International Quotidian Dialysis Registry to conventional HD patients in the DOPPS and demonstrated a 45% better patient survival with intensive HD (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.34 to 0.87).
Comparatively , in patients on short-daily HD, survival rates have been reported at 92% at 1 year and 73% at 3 years in a cohort of 262 patients from the United States and Europe. Moreover, lower risk for mortality also has been reported with short-daily HD compared with conventional HD. In fact, when daily home HD patients were matched to in-center HD patients using the US Renal Data System (USRDS) database, daily home HD was associated with a 13% lower mortality risk (HR, 0.87; 95% CI, 0.78 to 0.97).
Although most studies have compared intensive to conventional HD, a more recent cohort study from the Australia and New Zealand Dialysis and Transplantation Registry also compared survival with intensive home HD compared with PD. This study showed better patient survival with home HD (HR of mortality 0.47; 95% CI, 0.38 to 0.59) compared with PD.
The largest randomized studies comparing frequent HD to conventional thrice-weekly in-center HD are the FHN Daily Trial and Nocturnal Trial, two companion multicenter RCTs that randomized participants to either conventional thrice-weekly HD or frequent (six times per week) HD for 12 months. In the FHN Daily Trial, patients were randomized to either conventional thrice-weekly in-center HD or six times per week, in-center, short-daily HD. Conversely, patients in the FHN Nocturnal were randomized to either conventional or six times per week nocturnal home HD. However, as it was deemed not feasible to recruit sufficient participants to assess the individual outcome of mortality, these studies examined two coprimary composite outcomes: (1) death or change in left ventricular mass (LVM) and (2) death or change in physical-health score. Although frequent HD was associated with favorable coprimary outcomes in the FHN Daily Trial, there was no significant effect of frequent HD for either of the two co-primary composite outcomes in the FHN Nocturnal Trial. Recently, a long-term follow-up of these two trials has been published. Over a median follow-up of 3.6 years of the FHN Daily Trial, patients who had initially been randomized to frequent short-daily HD had a significantly lower mortality risk compared with those who underwent conventional HD (HR, 0.56; 95% CI, 0.32 to 0.99). In contrast, in the long-term follow-up of the FHN Nocturnal Trial, with a median follow-up of 3.7 years, the risk for mortality was significantly higher in the frequent group (HR, 3.88; 95% CI, 1.27 to 11.79). However, the results of these long-term studies should be interpreted cautiously as the FHN trials were not designed to detect mortality differences. Moreover, patients were free to modify their dialysis prescription after the initial 12 months and there was an exceedingly low mortality rate in the FHN Nocturnal Trial.
Cardiovascular Benefits
Cardiovascular disease remains the leading cause of mortality and morbidity in the ESRD population. LVH is well identified as an independent risk factor for mortality and cardiovascular events with significant prognostic value in ESRD patients. The prevalence of LVH increases as renal function declines and is present in up to 85% of incident dialysis patients. Studies in conventional HD and PD have shown that LVH progresses over time in the majority of patients. In contrast, reduction of left ventricular mass (LVM) has been well reported with intensive HD.
In a prospective Canadian RCT by Culleton et al., frequent nocturnal HD was associated with a significant mean reduction in LVM of 15.3 g ( P = 0.04) compared with conventional HD. Furthermore, in the FHN Daily Trial, LVM significantly decreased in the short-daily group compared with conventional HD (difference in change between groups of 13.8 g; 95% CI, 5.8 to 21.8). Conversely, in the smaller FHN Nocturnal Trial, no significant difference in LVM was observed. However, the small sample size and large proportion of patients without LVH at baseline could have explained the lack of apparent benefit in the nocturnal group.
Several observational studies also have demonstrated beneficial effects of frequent HD on LVM. In an observational cohort comparing 28 patients who converted from conventional to nocturnal HD with 13 control patients, Chan et al. reported a significant reduction in LVM with nocturnal HD (22% decrease from 147 to 114 g/m 2 ). In comparison, LVM increased in the controls (142 to 150 g/m 2 ). Similarly, in a prospective cohort study by Ayus et al. comparing 26 short-daily HD patients to 51 matched conventional HD patients, short-daily HD was associated with a 30% decrease in LVM, whereas no change was seen in conventional HD. A metaanalysis, including 38 single-arm studies, 5 crossover trials, and 3 RCTs, examining the effect of frequent or extended HD (home or in-center) also reported favorable reduction of LVM compared with conventional therapy, as well as improved left ventricular ejection fraction. Reduction of LVM with frequent HD is likely multifactorial in the context of improved clearance of uremic toxins, better blood pressure control, superior fluid management, and improved abnormalities of mineral metabolism. Downregulation of genes involved in cardiomyocyte apoptosis and fibrosis and improved endothelial dysfunction also have been demonstrated. In addition to beneficial effects on LVH, increased dialysis frequency also reduces left and right ventricular volumes and increases heart rate variability, which have both been shown to be associated with cardiovascular events and mortality.
The effect of intensive HD on LVM reduction appears to be much more important in patients with LVH at baseline, as seen in a post hoc analysis of the FHN trials. Moreover, recent studies also highlighted the important prognostic implication of LVH regression. In a single-center observational study of 144 intensive home HD patients from Toronto, Canada, regression or prevention of LVH was associated with a significantly lower risk for the composite endpoint of all-cause mortality, technique failure, or cardiovascular hospitalization (HR, 0.42; 95% CI, 0.21 to 0.84). Regression was defined as a reduction of >10% in LVM in patients with baseline LVH.
In addition, a lower cardiovascular hospitalization risk has been reported with frequent HD. When Medicare-enrolled daily home HD patients were compared with matched thrice-weekly HD patients by Weinhandl et al., daily HD was associated with a significantly lower risk for cardiovascular-related admission (HR, 0.89; 95% CI, 0.86 to 0.93). Similar beneficial results on cardiovascular-related hospitalization risk also were seen when daily home HD patients were compared with PD patients.
Blood Pressure
Improved blood pressure control has been reported consistently with frequent HD in observational, as well as randomized studies. In a meta-analysis, intensive HD was associated with significantly lower systolic, and diastolic blood pressure and mean number of blood pressure medications. Although improved fluid status plays a role in better blood pressure control, other established mechanisms with intensive HD have included decreased peripheral resistance, decreased plasma norepinephrine concentration, restoration of brachial artery responsiveness to hyperemia and nitrates, and increased baroreceptor sensitivity and compliance.
Mineral Metabolism
Improved phosphate control with decreased use of phosphate binders is extensively described with frequent HD regimens. In the FREEDOM trial, a prospective observational study of short-daily HD, frequent HD was associated with a significant decrease in serum phosphorus. Similar findings were described in the FHN trial and the more recent ACTIVE trial, which randomized patients to extended weekly (>24 hours) or standard (12 to 15 hours) HD. However, the effects of intensive HD on parathyroid hormone (PTH) levels appear variable. In an RCT by Walsh et al. comparing the effects nocturnal HD with conventional HD on mineral metabolism, beneficial effects on serum phosphorus and phosphate binders use were described, but there were no significant changes in intact PTH levels. Nonetheless, decline in PTH levels were more frequent in the nocturnal group than in the conventional group (61% vs. 20%; P = 0.003).
Sleep
Improvement in symptoms of sleep apnea has been demonstrated with intensive HD. More recently, studies have linked fluid overload to the pathogenesis of sleep apnea in patients with ESRD. Indeed, it has been shown that there is redistribution of extracellular fluid in the supine position, with interstitial fluid accumulation in the neck tissues and in the lungs, thus leading to increased upper airway collapsibility and pulmonary congestion. Consequently, reduction in fluid overload with frequent HD may result in improvement in apnea symptoms. Furthermore, the FREEDOM study demonstrated that short-daily HD was associated with better sleep quality, as measured by the Medical Outcome Study sleep survey. In fact, significant increased sleep adequacy with decreased sleep disturbances and nighttime awakening were reported with frequent HD. Similarly, there was significant improvement in symptoms of restless legs syndrome (RLS), assessed by the International Restless Legs Syndrome (IRLS) Study Group rating scale, with frequent HD. This was even more pronounced in patients with moderate to severe RLS at baseline.
Fertility and Pregnancy
ESRD is associated with decreased fertility and low conception rates. Moreover, pregnancy outcomes are poor with higher risk for intrauterine growth retardation, stillbirth, preterm labor, and preeclampsia. Although data are limited, better pregnancy outcomes have been reported with intensive HD. A recent cohort study compared 22 pregnancies on intensive HD in the Toronto Pregnancy and Kidney Disease Clinic and Registry to 70 pregnancies from the American Registry for Pregnancy in Dialysis Patients. Intensive HD was associated with higher gestational age, higher infant birth weight, and superior live birth rates.
In the setting of chronic kidney disease, numerous factors are thought to contribute to decreased fertility. Endocrine disturbances are present with abnormal follicular-stimulating hormone and luteinizing hormone levels leading to lower estrogen and progesterone concentrations and increased prolactin levels. In addition, dysregulation of the hypothalamic-pituitary-gonadal axis, menstrual irregularities, sexual dysfunction, anemia, and medications play a role. With more intensive HD, it is postulated that the increased clearance of uremic toxins may improve hypothalamic – pituitary – gonadal axis dysfunction and endocrine abnormalities. Furthermore, better blood pressure control with intensive HD also may lead to improved pregnancy outcomes.
Quality of Life
Impaired QoL is common in ESRD patients. As frequent HD includes various different treatment regimens that can be performed in-center or at home, the effects of frequent HD on QoL have yielded inconsistent results. In a RCT of frequent home nocturnal HD versus conventional HD by Culleton et al., frequent therapy was associated with improved selected kidney-specific domains of QoL, although there was no significant difference in overall QoL. More recently, the ACTIVE trial randomized patients to extended weekly (>24 hours) or standard HD (12 to 15 hours), either in-center or at home, and evaluated change in QoL using the EuroQol 5 dimension instrument (EQ-5D). At 12 months, change in EQ-5D score did not differ between groups, but the relatively high baseline scores of participants may have limited significant findings. However, in this study, both physical and mental component scores of the 36-Item Short Form Health Survey (SF-36) did significantly improve with intensive HD. Comparatively, in the FHN trial, one of the coprimary composite outcome included a patient-reported physical health score (RAND-36). Whereas participants in the FHN Daily Trial reported a significant higher score after 12 months compared with conventional HD, there was no significant difference in the FHN Nocturnal Trial. Additional analyses from the FHN trial showed that patients in the frequent daily in-center HD group had higher feeling thermometer scores, and that both nocturnal and short-daily groups had shorter dialysis recovery time compared with the conventional group. The feeling thermometer is a single question that asks patients to rate their health on a scale from 0 to 100, with 100 being perfect health. Shorter recovery time after HD also has been reported in observational studies.
The effect of frequent HD on depressive symptoms has been variable. In the FHN trials, no significant differences were found in either the Daily Trial or the Nocturnal Trial. Conversely, in the FREEDOM study, short-daily HD was associated with a significant decrease in Beck Depression Inventory (BDI) score and the proportion of patients with depressive symptoms decreased significantly after 12 months.
It should be noted that, although there is a physiological basis for escalation of dialysis dose for mineral metabolism, fertility, and cardiovascular benefits, there may not be a clear rationale for improved overall QoL with more intensive HD. It may be more realistic to expect positive changes in kidney-specific domains of QoL. Furthermore, the heterogeneity of patients (home vs. in-center, different treatment schedules) makes the true effect on QoL difficult to evaluate. For home HD patients, there is the added complexity of the dialysis procedure that needs to be considered. Limitations of QoL measurement tools should be taken into account.
Risks and Complications
Noninfectious Vascular Complications
With frequent HD schedules, the number of vascular access cannulations is higher. With increased vascular access use, the risk for vascular access complications, both infectious and noninfectious, is potentially higher.
In the FHN Daily Trial, Suri et al. reported a higher risk for first vascular access event (repair, loss, or hospitalization) in daily HD compared with conventional HD (HR, 1.76; 95% CI, 1.11 to 2.79). The majority of these events were repairs or losses. Among patients with arteriovenous (AV) access, the increased risk was even more pronounced (HR, 1.90; 95% CI, 1.11 to 3.25). In the corresponding Nocturnal Trial, similar trends were observed but these results failed to reach statistical significance. In an observational Australian study by Jun et al. of 286 patients receiving extended-hours HD, the number of weekly dialysis sessions was found to be associated with higher risk for vascular events. In fact, each one-session-per-week increase in dialysis frequency was associated with a HR of 1.56 (95% CI, 1.03 to 2.36) of adverse access-related event.
Infectious Complications
In patients with ESRD, infection is a major cause of mortality and morbidity, accounting for almost 25% of hospitalizations. In a study with daily home HD patients matched to conventional in-center HD patients using USRDS data, infection-related hospitalization was higher in the daily group (HR 1.18; 95% CI, 1.13 to 1.23). Vascular-access infection-related hospitalization was significantly higher in the daily group (HR, 1.39; 95% CI, 1.28 to 1.50) as well. However, these results may have been confounded by incomplete information regarding vascular access type and dialysis dose. Conversely, in the FHN trials, there was no overall difference in infection-related hospitalization between intensive and conventional HD.
Given more frequent vascular access use, recent studies have evaluated whether central venous catheter (CVC) use leads to worse outcomes in intensive HD patients by the same token as it does in conventional thrice-weekly HD patients. Indeed, similar to studies in conventional HD, two recent registry-based observational studies from Canada and the United States demonstrated that CVC use is associated with higher mortality and hospitalization rates compared with AV fistulae (AVF) and AV graft (AVG) use.
Nonetheless, an important factor to consider is the heterogeneity of patients on frequent HD. Moreover, multiple confounders exist when examining vascular access risks with frequent HD, namely differences in operator, infection control practices, frequency of treatment, and cannulation technique. In fact, cannulation technique is an important contributor to infection risk and this information is lacking in several observational studies. Although buttonhole cannulation may be possibly easier to perform at home, studies have indicated it leads to worse outcomes. In a systematic review by Wong et al. examining home HD patients, buttonhole cannulation was associated with higher risk for both local and systemic infections compared with rope-ladder technique.
Residual Kidney Function
Residual kidney function (RKF) is a well-known independent predictor of overall survival in patients with ESRD. RKF was examined in both the FHN Daily and Nocturnal trials. The difference in RKF was not as significant in the short-daily group, with comparable urine outputs at 4 and 12 months, as patients on conventional HD. On the other hand, in the nocturnal group, 52% of the patients were anuric at 4 months compared with 18% in patients on conventional HD ( P = 0.02). After 12 months, this number increased to 67% in the nocturnal group as opposed to 36% in patients on thrice-weekly HD. However, the FHN studies were likely not designed to detect changes in RKF. Moreover, it is unclear why a more pronounced decline of RKF was seen in the nocturnal group, but not seen with the short-daily group as the HD frequency in both groups was the same. Further studies are needed to better understand RKF trajectory with intensified HD schedules.
Technique Failure
Higher dialysis frequency may be challenging for patients and their caregivers, and this may lead to discontinuation of frequent HD and switch to a thrice-weekly regimen. To our knowledge, few studies have examined the association between dialysis frequency and technique failure in home HD. In a multicenter registry-based Canadian study by Tennankore et al. examining differences in technique survival between different home HD modalities, both short-daily and nocturnal home HD were associated with similar treatment survival when compared with conventional home HD.
There is scarce data examining technique survival in the setting of in-center frequent HD. In a multicenter cohort in the International Quotidian Dialysis Registry, technique failure occurred in 30% of patients receiving facility-based daily HD after a median of 10 months.
With increasing efforts to encourage frequent dialysis modalities, it is imperative to better understand technique survival and find strategies to help maintain patients on these therapies. Are there any facility-specific features that predict failure? Are technique failure rates changing with time? It is possible that expanding patient selection criteria may lead to higher discontinuation rates.
Clinical Indications
Frequent HD, particularly home HD, may be beneficial to several patient populations. Box 27.2 outlines situations in which frequent HD and home HD are appropriate as well as contraindications.
| Indications for frequent hemodialysis |
| Severe obstructive sleep apnea Resistant hyperphosphatemia with or without symptoms Persistent uremic symptoms Uncontrolled hypertension Refractory fluid overload Right heart failure Uncontrolled ascites Symptomatic intradialytic hypotension on conventional hemodialysis Excessive recovery time after conventional hemodialysis Women who are pregnant or planning to conceive |
| Potential candidates for home hemodialysis |
| Employed patients Patients attending school Patients who have failed peritoneal dialysis and wish to remain on a home modality Motivated patients wishing to perform therapy at home |
| Contraindications to home hemodialysis |
| Unstable medical conditions Lack of suitable vascular access Uncontrolled behavioral or psychological issues Contraindication to anticoagulation use Uncontrolled seizures Significant hemodynamic instability on hemodialysis Planned transplant within 6–12 mo |
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