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Improving patient outcomes in chronic kidney diseases with high dose and home haemodialysis is discussed
Tom Cornelis MD
Department of Internal Medicine,
Division of Nephrology,
Maastricht University Medical Centre,
Maastricht, The Netherlands
The final stages of kidney failure (known as end-stage renal disease [ESRD]) reduce survival and quality of life, but can be treated with renal replacement therapy. Kidney transplantation, especially living donation, offers the best outcomes but is not always possible and even suitable transplantation candidates often have to wait a long time before kidney transplantation may take place. The alternative to kidney transplantation is dialysis. Currently, most dialysis patients are treated with haemodialysis (HD). Another less frequently used dialysis modality is peritoneal dialysis (PD), whereby removal of toxic waste products and excess fluid occurs across the peritoneal membrane after instillation of PD solution into the peritoneal cavity.
Available for 70 years globally, more than two million people receive dialysis for chronic kidney disease (CKD). Nevertheless, albeit life sustaining, HD performed in the traditional thrice-weekly regime, which is the most commonly used dialysis technique worldwide, is unsatisfactory with a seven-fold increase in mortality compared to the general population, suboptimal quality of life, and high economic burden to society. In contrast to the native kidneys, HD is performed on an intermittent basis, which leads to unphysiologic fluctuations in the internal milieu of the patient. Furthermore, dialysis techniques are less efficient than the native kidneys for the clearance of larger uraemic toxins. The increased mortality in the dialysis population is mainly due to an increased risk of cardiovascular events, although infectious complications also play a significant role.1
The increased cardiovascular risk of dialysis patients in the short-term is mainly based on the occurrence of intradialytic hypotension, acute cardiac events including myocardial infarction and arrhythmias, as well as myocardial stunning.2,3 Hypotension is the most common acute complication during HD. The pathophysiology of intradialytic haemodynamic instability is multifactorial and includes underlying ischaemic and valvular heart disease, left ventricular hypertrophy (LVH) and diastolic dysfunction, autonomic nervous system and baroreceptor sensitivity impairment and impaired vascular refilling from the interstitial compartment due to arterial stiffness and hypoalbuminaemia. Hypotension may even ensue in serious complications such as myocardial or cerebral ischaemia, especially in patients with pre-existing cardiac and/or cerebrovascular disease.
In the long-term, dialysis patients suffer from LVH, cardiovascular calcifications, global systolic dysfunction due to repetitive myocardial stunning, as well as arterial hypertension. The presence of LVH is clinically important because it is associated with heart failure, cardiac arrhythmias, fatal myocardial infarction, decreased left ventricular ejection fraction, sudden cardiac death, and cerebrovascular events. In general, the development of heart failure with LVH results from depressed left ventricular systolic function and/or diastolic dysfunction. Risk factors for the development of LVH in CKD patients include anaemia, hypertension, ischaemic heart disease, and ageing. Furthermore, dialysis patients are often confronted with fluid overload especially when they are anuric. Also, it has been elegantly demonstrated that the long interdialytic interval (between the HD session on Friday and Monday or between the HD session on Saturday and Tuesday for the thrice-weekly HD regimens) is associated with an increased risk of cardiovascular mortality.4
What is high dose and home HD?
Most HD patients are dialysed these days in the hospital three times a week for four hours per session (conventional HD). Although its origins go back to the 1960s, home HD has been undergoing a significant revival over the last 20 years. This resurgence is related to observational data showing several benefits of home HD compared to conventional HD, including improved patient survival, better quality of life and reduced costs.5–7 Also, home HD increases the flexibility of the patient, and it allows patient exposure to different treatment regimens.
If HD is performed in an intensive setting (high dose HD), benefits on uraemia control, survival and quality of life may even further increase. Charra et al in Tassin reported dramatically improved survival of dialysis patients by extending the duration of thrice-weekly in-centre HD.8 High dose HD refers to HD with an increase in dialysis frequency (number of days per week) and/or session length above a standard conventional regimen of thrice-weekly four-hour HD. There are three predominant high dose HD schedules that are commonly identified:
Both long and long-frequent HD can be provided overnight while the patient sleeps (nocturnal HD [NHD]). SDHD and NHD can be delivered in the hospital, but preferably patients on high dose HD are dialysed in the home setting (high dose home HD) in order to avoid frequent transport to the hospital or dialysis centre. A summary of typical dialysis frequencies, session duration and blood and dialysate flows for conventional and high dose HD are presented in Table 1.
Clinical benefits of high dose and home HD
As described above, the complications of conventional intermittent HD may be related to the often-dramatic changes in the internal milieu associated with thrice-weekly HD treatments. More frequent and/or longer HD sessions may reduce the severity of internal environment disturbance by more physiologic correction of the internal milieu, by optimisation of fluid and uraemic toxin removal and by avoidance of the long interdialytic interval.4,9,10 A summary of the ample benefits of high dose HD is presented in Table 2.
Several studies have evaluated survival in SDHD and NHD. However, no sufficient randomised controlled trial (RCT) has been performed so far. Observational data show better patient survival rates for SDHD and NHD patients as compared to conventional HD. In addition, SDHD and NHD cohorts have equal survival rates as compared to deceased donor transplant recipients,11 although in the most recent retrospective cohort study of high dose home HD patients and kidney transplant recipients, kidney transplantation was associated with superior treatment and patient survival.12
Blood pressure (BP) reduction is one of the most consistent benefits of high dose HD in randomised and non-randomised studies. One of the first reports of improved BP control by means of high dose HD came from Tassin in France where an inverse correlation between mean BP measured by ambulatory BP monitoring and duration of dialysis session was found. The Frequent Haemodialysis Network (FHN) study showed a significant reduction in systolic BP among the NHD cohort after 12 months of –9.7 (–16.9, –2.5) mmHg with a significant decrease in antihypertensive agents. No difference was seen in the patients on conventional HD at the home setting, illustrating the importance of high dose HD (and not only of location) for BP control. NHD reduces BP by lowering total peripheral resistance and plasma norepinephrine levels. SDHD also improves BP control, but the speculated mechanism is via reduction in fluid overload.
Observational studies of SDHD and NHD cohorts as well as one RCT of NHD have reported improvement in left ventricular mass index as a marker of LVH, which is associated with infaust cardiovascular outcomes in CKD and dialysis patients.13 A recent meta-analysis of observational studies and data from RCTs looking at the effects of both frequent and extended HD on left ventricular geometry, reported improvement in left ventricular mass index in both groups. Furthermore, Jefferies et al. demonstrated, in a cross-sectional study, that more frequent HD regimens were associated with lower ultrafiltration volumes and rates compared with conventional in-centre HD. Intradialytic fall in systolic BP was reduced in SDHD groups and abolished in the nocturnal HD group. Frequent HD regimes were associated with less dialysis-induced myocardial stunning compared with conventional HD.
Optimisation of phosphate and mineral metabolism control, which is also associated with LVH, vascular calcifications and cardiovascular outcomes in dialysis patients, is described with extended HD and, to a minor extent, with SDHD. Long-frequent HD patients can most often be taken off phosphate binding drugs, and frequently require phosphate supplementation through the dialysate. In the long-term, improved control of hyperphosphataemia and secondary hyperparathyroidism by high dose HD may result in reduced risk of LVH and vascular calcifications.
The impact of high dose HD on quality of life (QoL) has been the subject of multiple studies and overall results show an increase in kidney-specific domains of QoL parameters. Quality of life in high dose HD may increase due to increased autonomy and functionality, reduced pill burden, liberalisation of diet and fluid intake, elimination of transport time (in home HD), continuation of employment and reduction of uraemic symptoms. In addition to QoL, mood improvement can be seen with high dose HD at the home setting.
Both SDHD and NHD have demonstrated improved sleep quality. The FREEDOM study showed a decreased prevalence of restless legs syndrome from 35 to 26% after 12 months of SDHD (p=0.05). NHD has been associated with a reduction in the frequency of sleep apnoea episodes.
Conception rates and outcomes of pregnancies are poor in patients on dialysis. Observational data show better outcomes in patients dialysing more than 12 hours per week and in patients with lower urea levels. In this context, high dose HD seems associated with the best pregnancy outcomes in patients requiring dialysis.14 It is postulated that high dose HD may partially restore the pituitary-hypothalamic axis by increasing toxin clearance. Also, a better control of fluid status and BP could have beneficial effects on pregnancy. In men, high dose HD could improve fertility by increasing testosterone level and decreasing hyperprolactinaemia.
Risks of high dose HD
Frequent HD may potentially lead to more vascular access complications due to more frequent cannulation. In the FHN trial, patients on SDHD had a shorter time to first vascular access event compared with the conventional HD group. Most of these events were vascular access repairs as opposed to losses. A similar trend was found in the nocturnal arm of the FHN study. In an in-depth review of available studies of vascular outcomes in frequent HD compared to conventional HD, we found that consolidating a total number of 1540 access years for frequent HD and a total number of 2284 access years for conventional HD, frequent HD was associated with a higher vascular access event rate as compared with conventional HD (difference = 6.7 events per 100 patient years, p=0.009 for all included studies).15
The rope-ladder technique is the predominant cannulation method of arteriovenous fistulas and grafts. For every HD, two new sites are chosen for needle placement to allow good healing of the puncture wound. Buttonhole (constant site) cannulation is an alternative technique whereby needles are inserted each time at exactly the same spot using the same insertion angle and the same depth of penetration for each consecutive dialysis session. Buttonhole cannulation is commonly used in frequent HD because it may result in decreased pain, faster cannulation and lower risk of haematoma. However, concerns have been raised recently regarding the safety of this method, especially at the level of infections. Several studies have indeed highlighted the increased risk of local and systemic buttonhole infections in patients on high dose HD.
Residual kidney function (RKF) in dialysis patients is associated with clinical benefits. A significant decline in RKF is observed in the first year after dialysis initiation, especially in conventional HD patients. Recently, the nocturnal FHN study showed a faster reduction in RKF in patients on NHD as compared to conventional HD. This may be related to increased changes in BP and fluid state, reduction in osmotic load and possible increased inflammatory response and platelet activation. More studies are required to confirm the finding of faster RKF loss in high dose HD and also to elucidate the potential underlying mechanisms for this observation.
Who is eligible for high dose and home HD?
Patient motivation is essential for the feasibility of high dose and home HD. In this setting, there are few absolute contraindications for this treatment such as lack of suitable vascular access (in home frequent HD), uncontrolled psychosis and lack of caregiver (if the patient is dependent and if there is no availability of dialysis nurses) (in home HD).
Lack of motivation/interest, unwillingness to change, learned helplessness, fear of isolation, perceived burden on caregivers and fear of cannulation are known barriers to home HD. However, these barriers can often be overcome by adequate pre-dialysis education, motivational training of the patient and caregiver, nurse-assisted cannulation, nurse-led home visits, a well-defined nursing/technical support system for patients and provision of respite care.
Target populations for high dose home HD
Target populations for high dose home HD could be classified in established, suggested and emerging indications for this modality.16 Patients who present with persistent extracellular fluid overload, severe hypertension and/or LVH, haemodynamic instability, resistant hyperphosphataemia and pregnant women or women on dialysis who wish to conceive are established candidates for high dose home HD. Sleep apnoea, reduced QoL, uraemic symptoms and persistent inflammation oxidative stress should also trigger the initiation of high dose home HD in the dialysis patient (suggested target populations). In addition to these potential target populations, there are emerging patient populations for whom high dose home HD may also be considered. Emerging patient populations range from caregiver-dependent patients because patients and caregivers generally prefer a home-based dialysis therapy, crash starters, employed patients, transplant and PD failures, morbid obesity and elderly ESRD patients.17 Also, one case with severe hyperoxaluria who benefitted from frequent nocturnal HD has been described in the literature.18
Further research and observational data are necessary to convince as many nephrologists all over the world as possible that high dose and home HD may offer a very good alternative to many ESRD patients. Also, studies should assess the balance between benefits and risks of high dose home HD. However, we are convinced that clinical dialysis practice should focus on the opportunities of home-based dialysis therapies rather than on barriers. Bringing therapies to the patients homes will also allow them to incorporate health and disease in their daily lives, a strategy which may support them to continue daily life activities including employment rather than putting the emphasis on medicalisation of disease-related issues.
Convincing patients of medical strategies starts with the healthcare team. A different attitude towards home-based dialysis should therefore be strived for. By making home dialysis a basic theoretical and practical part of nephrology training for medical trainees and nurses a better perception and appreciation of its ins and outs may be achieved. Once the renal care team is convinced, pre-dialysis education should focus on the ‘home dialysis (home HD or PD) first’ principle. Experience indicates that patients should start directly onto home dialysis, as starting with in-centre HD stimulates the development of ‘learned helplessness’. Support from governments, medical administrations and healthcare companies is indispensable for the development of this strategy. Also, adequate infrastructure with a separate building in or outside the hospital for home HD training, support, education and clinics, as well as facilities for respite care is necessary. Lastly, support of the patient and his/her family by an enthusiastic social worker and psychological evaluation in combination with rehabilitation, are crucial elements in the holistic approach of the ESRD patient who requires dialysis treatment.
It should be emphasised that the role of PD in the treatment of ESRD patients remains very useful. Especially at the time of transition from pre-dialysis to dialysis, PD may be an excellent alternative to home HD, also given consistent data demonstrating an association between preservation of residual kidney function and PD therapy. However, once residual kidney function deteriorates, timely measures (such as education of patient and partner about home HD, and home HD installation), should be taken to allow an uncomplicated switch from PD to home HD. This should be the final goal of pre-dialysis and dialysis education and care: provide a continuum of home based ESRD care to our patients.