Anemia management for home dialysis including the new US public policy initiative

Graphical Abstract

Abstract

Patients with end-stage kidney disease (ESKD) requiring kidney replacement therapy are often treated in conventional dialysis centers at substantial cost and patient inconvenience. The recent United States Executive Order on Advancing American Kidney Health, in addition to focusing on ESKD prevention and reforming the kidney transplantation system, focuses on providing financial incentives to promote a shift toward home dialysis. In accordance with this order, a goal was set to have 80% of incident dialysis patients receiving home dialysis or a kidney transplant by 2025. Compared with conventional in-center therapy, home dialysis modalities, including both home hemodialysis and peritoneal dialysis, appear to offer equivalent or improved mortality, clinical outcomes, hospitalization rates, and quality of life in patients with ESKD in addition to greater convenience, flexibility, and cost-effectiveness. Treatment of anemia, a common complication of chronic kidney disease, may be easier to manage at home with a new class of agents, hypoxia-inducible factor-prolyl hydroxylase inhibitors, which are orally administered in contrast to the current standard of care of i.v. iron and/or erythropoiesis-stimulating agents. This review evaluates the clinical, quality-of-life, economic, and social aspects of dialysis modalities in patients with ESKD, including during the coronavirus disease 2019 pandemic; explores new therapeutics for the management of anemia in chronic kidney disease; and highlights how the proposed changes in Advancing American Kidney Health provide an opportunity to improve kidney health in the United States.

End-stage kidney disease (ESKD) has been increasing worldwide, and nearly 6 million patients are expected to need renal replacement therapy (i.e., dialysis or transplant) by 2030.¹ In the United States (US), the prevalence of ESKD increased by 91% between 2000 and 2017 to 746,557 cases, primarily attributed to longer survival of patients.² By 2030, the incidence of ESKD in the US is projected to increase by 11%–18% and the prevalence is expected to rise to 1.26 million patients.³ Common risk factors for progression to ESKD include diabetes, male sex, and proteinuria (16%, 37%, and 64% increased risk, respectively).⁴ Comorbid anemia (hemoglobin [Hb] levels <13 g/dl in men and <12 g/dl in women⁵) increases in severity with declining kidney function.^6,7 Because of the high clinical and economic burden of care with dialysis-dependent patients, particularly those with comorbid anemia, treatment modalities that improve care and are cost-effective are needed to manage the increasing health care demands.

Public Policy Intiative to Improve ESKD Outcomes

In an effort to improve care for patients with chronic kidney disease (CKD) or ESKD, the Executive Order on Advancing American Kidney Health (AAKH) was issued in July 2019, with 3 general aims: to prevent progression to ESKD and to decrease associated mortality through better diagnosis, treatment, and preventive care; to lessen the cost burden via payment incentives for treatment alternatives such as home dialysis and patient education; and to reform the transplantation system and encourage the development of artificial kidneys.⁸ In response, the US Department of Health and Human Services set specific benchmarks: achieve 25% reduction in the number of US patients who develop ESKD by 2030; have 80% of incident US patients receiving home dialysis or transplantation by 2025; and double the number of available kidneys for transplantation by 2030.^8,9

Several in-progress or newly-initiated measures will assist in meeting the goals of the AAKH. To help to achieve its first aim, the AAKH calls for an awareness campaign to enhance knowledge about kidney disease,⁸ because 90% of the 37 million adults in the US estimated to have CKD are unaware of their condition.¹⁰ To incentivize quality, advanced care by primary care physicians as opposed to fee-based services, the US Centers for Medicare & Medicaid Services will initiate the Primary Care First Model in 2021, which aims to improve health outcomes including for those with chronic and/or complex conditions.¹¹ The Centers for Disease Control and Prevention’s CKD Surveillance System¹² and the National Kidney Disease Education Program CKD e-Phenotype Working Group¹³ intend to improve detection of CKD in the population and to manage risk factors. Because a considerable proportion of patients with advanced CKD requiring kidney replacement therapy are elderly with physical and psychological limitations and multiple comorbidities, special consideration should be given in a joint decision-making process for the relative risks and benefits of initiating different dialysis modalities, including the decision to pursue replacement therapy.

Dialysis Modalities in ESKD

A key aim of the AAKH directive and US Department of Health and Human Services is to reduce costs via an emphasis on home dialysis modalities. Current dialysis modalities for patients with ESKD are hemodialysis (HD), either in center (IHD) or at home (HHD), and peritoneal dialysis (PD), a home-based treatment (Table 114, 15, 16, 17, 18, 19).

Table 1.

Characteristics of dialysis modalities

Characteristic	Conventional hemodialysis16, 17, 18	Short daily hemodialysis16	Nocturnal hemodialysis15,16	Continuous ambulatory peritoneal dialysis16	Automated peritoneal dialysis16
Location	In center	In center or at home	In center or at home	At home	At home
Sessions per week	3	6–7	5–7	4–6 times daily	Daily
Time per session, h	3–4	2–3	6–9	3–5	8–9
Contraindications14,19	Absence of vascular access or prohibitive cardiovascular instability	Absence of vascular access or prohibitive cardiovascular instability; for at- home, inability of patient/caregiver to perform	Absence of vascular access or prohibitive cardiovascular instability; for at- home, inability of patient/caregiver to perform	Obliteration or peritoneal cavity, nonfunctional membrane, catheter access not possible, inability of patient/caregiver to perform	Obliteration or peritoneal cavity, nonfunctional membrane, catheter access not possible, inability of patient/caregiver to perform

HD is the most common maintenance modality for patients with prevalent ESKD in the US (63% of patients, with the remaining 7% on PD and 30% with a functioning transplanted kidney). Of those receiving HD, 98% received IHD and only 2% used HHD.² Although utilization of HHD increased by 121% in 2017 compared with 2007, it represented only 4% of the modalities used in patients with incident ESKD.² In economically comparable countries, a higher proportion of patients on dialysis received home-based therapies, with >25% in Finland (18% PD, 8% HHD) and Canada (20% PD, 5% HHD) and >50% in Hong Kong (69% PD, 3% HHD). In addition, a higher percentage of patients with prevalent ESKD were treated with a kidney transplant in 2018 (>50% in Norway, Finland, Sweden, the UK; within 35%−45% in Canada and Hong Kong), although ESKD incidence in these countries was approximately 2 (and in some cases more) times lower than in the US.²⁰ In the US in 2017, preemptive kidney transplantation decreased with age in patients with incident ESKD and was more common in younger patients (20.8% in patients aged 0−21 years) than older patients (0.2% in patients 75 years or older).²

Clinical outcomes and mortality among dialysis modalities

Results from a prospective, multicenter study conducted over 6 months and a retrospective cohort study with 2-year follow-up illuminated a concern with patients undergoing common 3-times-weekly IHD with 2-day interdialytic interval; this modality was associated with increased arrhythmias, mortality, and hospitalizations (P < 0.001 for each) on the first day of weekly dialysis treatment after the interdialytic interval.^21,22 Longer HD session times improve hospitalization and mortality rates due to better clearance of small and larger molecules (e.g., phosphorus) as well as slower ultrafiltration rates,^23,24 but the risk for these adverse events remains higher on the first day of HD within a given treatment week after the interdialytic interval, even with longer dialysis sessions (i.e., >250 minutes).²⁵ More frequent dialysis has also been shown to improve outcomes. Patients randomized to 6 versus 3 times per week IHD had significantly better composite outcomes of death or increase in left ventricular mass, death or decrease in physical health, and significantly improved control of hypertension and hyperphosphatemia.²⁶ However, increased patient burden and health care costs with more frequent or extended IHD may outweigh these favorable results.

Home dialysis may provide an opportunity to improve clinical outcomes because it is more amenable to patient lifestyles and can be performed more frequently to eliminate the interdialytic interval without proportional increases in costs and the inconvenience of frequent trips to a center. However, it is important to note that most of the published comparisons of IHD, HHD, and/or PD are observational in design, with few randomized controlled trials and prospective cohort studies.^27,28 In addition, patients receiving home dialysis tend to have fewer comorbidities than those on IHD,^14,27,29 which is a confounding factor for comparisons.

Home dialysis is at least as effective as IHD and may be associated with similar or even lower mortality.³⁰ In patients who were eligible for either IHD or PD (i.e., had similar health status), similar risks of death were seen for each dialysis modality.³¹ Comparable survival rates after 2 years were observed between HD and PD (both either in center or at home),³² whereas in another study, those receiving HHD showed significantly greater median survival after dialysis initiation (18.5 years) compared with matched cohorts for PD (15.0 years) and IHD (11.9 years).³³ In addition, an observational study found a nearly 50% lower adjusted mortality risk with conventional or frequent/extended HHD compared with conventional IHD.³⁴ However, selection bias toward healthier patients and differences in dialysis dose, patient education, and socioeconomic factors may have contributed to differences in these studies showing survival advantage with HHD versus PD.

With regard to cardiovascular (CV) outcomes, frequent nocturnal HHD was associated with significant reductions in left ventricular mass,^35,36 and both diurnal and frequent nocturnal HHD improved hypertension, resulting in a reduction in antihypertensive medication use.^36,37 Conversely, a small randomized clinical trial in patients on conventional IHD versus nocturnal HHD did not find any significant improvements in the composite outcome of death/left ventricular mass reduction but did recapitulate results with better hyperphosphatemia and hypertension control.³⁸

All-cause hospitalization rates appear generally similar between home and in-center dialysis, despite the fact that patients selected for home dialysis are often younger and healthier than their IHD counterparts, and they are dependent on the underlying cause of hospitalization. Differences in cause-specific hospitalization rates by modality are apparent. In a retrospective cohort study, patients on assisted PD had similar hospitalization rates compared with patients receiving IHD, but dialysis-related hospitalizations were higher in the PD group, partly due to peritonitis.³⁹ Another comparison with United States Renal Data System data of patients on daily HHD and those on 3-times-weekly IHD found similar all-cause hospitalization rates but 11% lower rates for cardiovascular disease (CVD)-related admission.⁴⁰ Furthermore, patients on HHD in this study had 18% higher rates for infection-related admission, possibly due to either a direct increase in infection risk from more frequent dialysis or diminished infection control practices with home dialysis equipment relative to in-center procedures.⁴⁰ Composite hospitalization rates from CV-, infectious-, and vascular access–related causes were lower in patients using daily HHD compared with PD but were not different from IHD.⁴¹ In contrast, conversion to nocturnal HHD from IHD was associated with a significant decrease in composite dialysis- or CV-related hospitalization admission rates, likely due to a greater dialysis duration and efficacy (higher Kt/V). Nocturnal dialysis may further allow for better anemia management and phosphate control through increased clearance of uremic toxins that potentially inhibit erythropoiesis and adequate phosphate removal.⁴² Supporting this, improvements in serum phosphate levels and blood pressure and decreases in erythropoiesis-stimulating agent (ESA) doses were reported in patients switched from conventional IHD to in-center nocturnal HD, which may be an appropriate option in long-term dialysis patients unable to perform HHD.¹⁵ Although home dialysis modalities in general do not seem to increase overall hospitalization rates, proper technique, environment, and training are important to prevent infection-related hospital admissions and readmissions. However, the paucity of information regarding dialysis frequency, duration, and dose regarding HHD in many observational studies limits the interpretation of benefits of HHD relative to IHD.

Quality of life and flexibility of the home dialysis schedule

A literature review and meta-analyses found similar or marginally better quality of life (QOL) outcomes between HHD or PD compared with IHD.^16,43,44 Higher health-related QOL scores in various symptom domains such as kidney disease composite summary score and physical composite summary score were seen with PD compared with patients on HD early after dialysis initiation (i.e., 3 months), but many of these differences lost their significance after prolonged treatment (up to 2 years) with each modality.⁴⁵ Patients who switched from IHD to PD or HHD exhibited increases in some QOL measures including the Burden of Kidney Disease and Effects of Kidney Disease subscales of the Kidney Disease and Quality of Life survey, whereas patients who switched from home-based dialysis to IHD showed decreases in the Physical Component Summary.²⁹

Despite similar QOL between home and in-center dialysis modalities, home dialysis offers an advantage with respect to time and flexibility. Dialysis is a lengthy procedure, and compared with therapies for other chronic health conditions, it is the most time-consuming.⁴⁶ Patients with ESKD rated “dialysis-free time” among their top 4 outcomes of importance when considering interventions.⁴⁷ In addition to the time needed for the dialysis procedure itself, travel to the dialysis center 3 times a week increases the time burden, particularly for patients in rural areas.¹⁵ Highlighting the effect of IHD on patients, a multiclinic, discrete choice experiment in Australia found that patients were willing to trade off 7 or 15 months of life expectancy to reduce the frequency of in-center visits or to increase their ability to travel.⁴⁸ Importantly, patients on IHD and their families should be encouraged to interact with other patients. Such socialization is a key aspect of patient education potentially influencing choice of dialysis modality and formal engagement between patients as part of predialysis education may aid initiation and increase preference for home dialysis.⁴⁹

Anemia management in ESKD

Comorbid anemia is common in ESKD, occurring in over 50% of patients.^6,7 Decreased erythropoietin (EPO) production, functional iron deficiency or absolute iron deficiency due to impaired absorption of dietary iron and blood loss from HD, inhibition of erythropoiesis under uremic conditions, accelerated destruction of red blood cells (RBCs) by certain uremic toxins, and chronic inflammation all contribute to the severity of anemia of CKD.⁵⁰ Routine evaluation of Hb levels and iron status is important to determine the appropriate course of treatment of anemia.^51,52 Anemia screening in kidney transplant recipients is also important, as post-transplantation anemia is common (approximately 51% at 6 months after transplant) and is associated with higher mortality and graft failure.⁵³ Anemia is treated similarly in patients with CKD or ESKD whether or not they receive dialysis, that is, with exogenous iron therapy, usually i.v. in patients on dialysis, and ESAs.^5,52 RBC transfusion can be used if ESA therapy is not effective or if the risk of ESAs outweighs their benefits but is otherwise recommended to be avoided in the management of chronic anemia, particularly in patients eligible for kidney tranplantation.^5,52 Resistance to ESA therapy is a common challenge with anemia treatment, primarily due to iron deficiency and inflammation that impede the response to ESAs. In addition, accumulation of uremic toxins during CKD progression may cause ESA hyporesponse by inducing hemolysis or suppressing the key oxygen-sensing system, hypoxia-inducible factors (HIFs). Treatment with ESAs or HIF stabilizers (discussed later) does not increase survival of RBCs but may compensate for hemolysis or reduced EPO transcription by increasing RBC production. In addition to enhancing erythropoiesis, treatments aimed to reduce the generation or retention of uremic toxins in patients with CKD and ESKD represent an important therapeutic strategy to improve outcomes with anemia management.⁵⁴

Home dialysis modalities may offer certain advantages for anemia management. Although a meta-analysis of 14 studies showed no difference in Hb levels, ferritin, or transferrin saturation in patients receiving HD or PD,⁵⁵ other studies comparing nocturnal HHD with conventional HD found significant improvements in Hb levels and decreases in ESA dose from baseline at 6 months after patients switched from conventional HD (4 hours, 3 times weekly; dialysate flow rate of 500–750 ml/min) to nocturnal HHD (6−8 hours, 5−6 nights/wk; dialysate flow rate of 350 ml/min)⁵⁶ and in patients on nocturnal HHD (6−9 hours nightly; dialysate flow rate of 300 ml/min) versus conventional HD (4−5 hours, 2−3 times/wk; dialysate flow rate of 500 ml/min) for at least 2 years,⁵⁷ presumably due to improved clearance of uremic toxins stemming from increased dialysis frequency and dose. A subset of patients (up to 20%) with anemia of CKD, particularly those on HD, exhibit a hyporesponse to ESA treatment, often leading to increased ESA dosing. Notably, ESA hyporesponders have a higher mortality risk, rate of major cardiovascular events, and health care utilization and costs than patients with a normal ESA response, the worst outcomes being in chronic hyporesponders versus intermittent hyporesponders.58, 59, 60 Sustained benefits of nocturnal HHD suggestive of decreased ESA resistance (i.e., approximately 30% lower ESA dose after 4 years of treatment) were observed compared with conventional IHD or hemodiafiltration.⁶¹

New therapeutic options to treat anemia are important to consider in the context of ESA resistance and at-home dialysis (Table 2^5,62, 63, 64, 65, 66, 67, 68, 69, 70, 71). The current standard of care therapies of iron and ESAs given to patients on dialysis are usually i.v.-administered, placing another burden on patients and caregivers using home dialysis. Hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors, as discussed extensively by others in this supplement, are a new class of oral agents that have been shown to respectively raise or maintain Hb levels in ESA-naïve or ESA-converted HD patients with anemia.^62,72, 73, 74, 75, 76 In patients with ESKD who were ESA-naïve or ESA-converted and receiving PD, treatment with the HIF-PH inhibitor roxadustat increased Hb to stable target levels in a randomized phase 3 trial.⁷⁷ A study assessing the effect of dialysis modality on pharmacokinetics of daprodustat found that although Hb levels were maintained within the target range in patients receiving PD, higher doses of daprodustat were needed for patients on HD.⁷⁸ The oral route of delivery of HIF-PH inhibitors makes them particularly suitable in the treatment of anemia of CKD in the home dialysis setting due to their ease of administration and because they obviate the need for i.v. access as is needed with ESAs. However, the pill burden in patients on maintenance HD is high and may result in poor or nonadherence to oral medications, contributing to increased morbidity and mortality.⁷⁹ Nevertheless, an oral agent for anemia management would be an effective measure to limit exposure of vulnerable patients to infectious organisms, as evidenced by the recent pandemic, eliminating the need to travel to an infusion center. Several HIF-PH inhibitors have shown efficacy in correcting anemia of CKD and have been well tolerated in clinical trials, including in patients on HD. Elucidation of their putative, nonhematologic, pleiotropic actions on metabolism, cardiovascular homeostasis, angiogenesis, and tumor growth will require long-term studies.⁸⁰

Table 2.

Advantages and disadvantages of therapies for anemia of chronic kidney disease

Anemia treatment	Advantages	Disadvantages
Oral iron	•Oral agent, so patient may self-administer at home	•Decreased efficacy relative to i.v. iron in dialysis patients5 •Gastrointestinal adverse effects5 •Variable gastrointestinal absorption5
i.v. Iron	•Increased efficacy relative to oral iron5	•Administration is typically performed at a center •Doses must be managed to avoid iron overload and systemic inflammation63
Short-acting ESAs	•May reduce fatigue and improve HRQOL64 •Reduced need for RBC transfusions65	•Administration is typically performed at a center •Frequent (3-times-weekly) administration •Supplemental iron is often needed5 •Higher doses to reach Hb targets may increase risk of adverse CV outcomes64
Long-acting ESAs	•May reduce fatigue and improve HRQOL64 •Reduced need for RBC transfusions66 •Potentially more cost-effective than short-acting ESAs64,67	•Administration is typically performed at a center •Supplemental iron is often needed5 •Higher doses to reach Hb targets may increase risk of adverse CV outcomes64 •May increase risk of mortality compared with short-acting ESAs68
Red blood cell transfusion	•An alternative for patients in whom ESAs are ineffective5	•Administration is performed at a center •Adverse events such as allosensitization, blood volume overload, blood-borne infections, fever, hyperkalemia, iron overload5
HIF-PH inhibitors	•Oral agent, so patient may self-administer at home •Noninferior to ESAs in raising or maintaining Hb levels62,69,70 •May reduce need for supplemental iron71	•Long-term safety data needed

CV, cardiovascular; ESA, erythropoiesis-stimulating agent; Hb, hemoglobin; HIF-PH, hypoxia-inducible factor-prolyl hydroxylase; HRQOL, health-related quality of life; RBC, red blood cell.

Economic considerations of home dialysis

ESKD represents a large economic burden in the US, as patients with ESKD comprise 1% of the Medicare population but 7.2% of all Medicare claims ($35.9 billion in 2017).^17,81 Peritoneal dialysis is less expensive per patient per year than IHD ($78,159 vs $91,795, respectively, in 2017),² and a systematic review evaluating the cost-effectiveness of HD modalities found that HHD is more cost-effective over the long term (i.e., 5–10 years) compared with IHD.⁸² In most studies included in the systematic review, patients in HHD versus IHD cohorts were either demographically similar with respect to major comorbidities (e.g., CVD and diabetes), self-matched after switching from an in-center conventional to home modality, or selected from a low-risk patient population (i.e., patients with low comorbidities). However, candidates for HHD are often younger and healthier, so it is possible these results are not generalizable to all HD patients. In older patients or those with multiple comorbidities, HHD may be a less cost-effective and less attractive option compared with IHD due to technique failure, longer duration of training, or potentially increased risk of mortality.⁸² In 2011, US Centers for Medicare & Medicaid Services launched a prospective payment system for ESKD, which bundled dialysis service medications, including ESAs, and other dialysis-related costs into 1 payment per treatment as well as paying for home dialysis training.⁸³ The measure was meant to equally incentivize use of home dialysis (i.e., PD) and IHD by making their reimbursement equivalent.⁸⁴ The number of patients on home dialysis (both PD and HHD) increased by 15% in the 2 years after implementation.⁸⁴ Even though the prospective payment system only incentivized home dialysis for Medicare recipients, home dialysis also concomitantly increased in patients with other forms of insurance.⁸⁵

Future initiatives of the AAKH seek to improve access and quality of patient-centered treatment options while reducing costs. The AAKH mandates a Medicare physician payment model with incentives based on greater usage of home dialysis and transplantation to facilitate optimal patient care.⁸ The ESRD Treatment Choices model, which will positively adjust Medicare payments to facilities for home dialysis, effectively de-incentivizes IHD and is expected to decrease Medicare spending by $185 million over 6.5 years.^86,87

On the patient level, currently nonreimbursed, added out-of-pocket costs such as utilities and possibly home infrastructure changes (e.g., plumbing, electrical)⁸⁸ may markedly deter patients from adopting conventional home HD. Patients may achieve cost savings using alternative home dialysis platforms that do not require dedicated infrastructure, such as the NxStage System One (NXStage, Lawrence, MA).^89,90 Certain socioeconomic conditions, including nonconducive accommodations or lack of home ownership are also considerations for uptake of home dialysis modalities in the US.⁹¹

On the other hand, the financial burden associated with decreased patient work productivity or inability to work due to dialysis may be offset by home modalities that preserve the capacity to remain employed. Compared with IHD, patients on home dialysis have more control over choosing dialysis times, which may be more compatible with employment outside the home,⁹² even more so when physician visits are performed via telehealth.⁴⁶ Several studies have shown higher rates of employment with home dialysis (HHD or PD) compared with IHD.^92,93 Anemia had no effect on whether patients maintained employment at the start of dialysis in an analysis of United States Renal Data System registry data. However, treatment of anemia of CKD with EPO was higher in those who were employed versus unemployed (67% vs. 33%, respectively).⁹²

Other barriers to home dialysis and potential solutions

A large barrier to the uptake of home dialysis is that many patients are not presented with the option. Only 34% of ESKD network patients in the US were presented with the option of PD and only 12% with the option of HHD.⁹⁴ Despite this, most patients with ESKD (78%) were assessed as medically and psychosocially eligible for PD in a North American study.⁹⁵ In addition, patients reported a preference for PD over IHD (42% vs. 33%) during predialysis care or within the first month of dialysis, mainly due to the opportunity for home treatment.⁹⁶ Most patients on PD in the US reported a positive (53%) or very positive (43%) perception of PD and only 4% of patients had a negative perception, with the most commonly reported disadvantages including a bloated or full sensation from abdominal PD fluid and having personal space taken up by PD supplies, each in roughly one-third of PD patients.⁹⁷ Many US nephrologists may not prescribe home dialysis for their patients with ESKD due to misconceptions and a belief that it may be too burdensome to patients.⁹⁸ Nephrology health care providers in the US receive little to no training in home dialysis or PD access in nephrology fellowship programs^98,99; intuitively, this will present a major barrier to uptake of home dialysis. Gender differences may influence initial dialysis modality utilization and outcomes. Despite ostensibly higher CKD prevalence, women seem less inclined than men to initiate dialysis, which can lead to reduced care access. In the US and Europe, women also are less likely to use arteriovenous access to initiate HD, which is associated with a survival benefit, compared with men.¹⁰⁰ Regarding home dialysis modalities, women were 12% more likely to initiate PD,¹⁰¹ but the incidence and prevalence of home HD is higher in men than women in the US.¹⁰² Racial disparities may also play a role, as minority groups may have limited awareness of home dialysis.¹⁰³

Patient and caretaker involvement in dialysis choice and prior education are key components to successful home dialysis. Educational intervention before dialysis choice significantly increased the proportion of patients choosing self-care dialysis compared with matched controls¹⁰⁴ and was associated with a 2- to 4-fold increase in the odds of choosing PD and a 3.5-fold increase in the odds of receiving PD.¹⁰⁵ A discrete choice study found that patients preferred home dialysis to IHD when there was greater treatment flexibility, greater well-being, higher nursing support, or ability to dialyze during the day or evening (vs. day only).¹⁰⁶

Other potential issues with home dialysis among patients and their caregivers may include anxiety over the ability to perform a medical procedure at home, feelings of social isolation and less frequent monitoring, and burden to caregivers.¹⁰⁷ Although respite care programs may support stress relief for caregivers and provide a mental benefit for patients on home dialysis by fulfilling social interaction needs,108, 109, 110 such concerns may lead to the discontinuation of home dialysis and a transition to IHD, with higher mortality rates and higher resource utilization. Physical and cognitive barriers may also deter the use of home dialysis.¹¹¹ Frailty was associated with a greater than 2-fold increased risk of unplanned transition to IHD or all-cause death in patients on home dialysis.¹¹² In older patients with diabetes, significantly higher mortality rates were seen in patients aged 45–64 and >65 receiving PD compared with age-matched groups undergoing HD (11% vs. 19%).³² Another study found that diabetes and a history of CVD also contribute to higher mortality rates with PD.¹¹³ Assisted PD, which can involve personal support workers to aid in more physical tasks and/or nurses to provide more medical support, and videodialysis, a form of telemedicine, have helped to ameliorate these barriers in countries outside the US.^111,114 However, there is no specific provision in the AAKH to patients or caregivers for overcoming barriers to home dialysis, including assisted home dialysis.⁸⁶ Because AAKH emphasizes home dialysis, it may not benefit patients in unstable housing or address socioeconomic inequities in dialysis care. A sustainable funding model and revamped administrative processes may be needed to optimize care and overcome inequities.

Some of the adverse effects associated with home dialysis are related to the frequency of dialysis rather than location. Because some blood is lost during HD, it is perhaps not surprising that total blood loss was significantly higher in patients receiving nocturnal HHD or daily IHD compared with those on conventional 3-times-weekly IHD.¹¹⁵ Any resultant iron deficiency can be corrected with iron supplementation and ESA dose adjustment and, potentially, with HIF-PH inhibitors through hepcidin inhibition.⁵⁰ Interventions related to vascular access, particularly for those with an arteriovenous fistula or graft, were also more frequent in patients randomized to IHD 6 versus 3 times per week.^26,116 Notably, adverse events rates were significantly higher in IHD than in HHD, including dysgeusia, dizziness, and back and neck pain.¹¹⁷

PD technique failure, defined as any switch to HD for ≥ 30 days, has been shown to occur in 39%–54% of patients on incident PD.^118,119 Most of the instances of PD technique failure were due to infection (52%), with the remaining due to inadequate dialysis (19%), mechanical failure (18%), and social reasons (11%).¹¹⁸ Demographic, clinical, and social characteristics associated with risk of PD technique failure in the US include male sex, black race, high systolic blood pressure, being retired or disabled, and being on Medicaid.¹¹⁹ Peritonitis in PD patients is associated with significantly increased risk of all-cause, CV, and infection-related mortality.¹¹³ HHD may be a suitable option for patients failing PD, as clinical outcomes were maintained or improved in patients switched to nocturnal HHD from PD,¹²⁰ and lower risk of death and higher incidences of kidney transplant were seen in patients switched to HHD from PD compared with matched controls of patients switched to IHD from PD.¹²¹

Several challenges exist for the AAKH to meet its goal to increase home dialysis.¹²² Obstacles involve expanding nephrology fellowships to include training on home dialysis modalities, transplant medicine, and diagnosis and treatment of comorbidities (e.g., anemia and diabetes), and incentivizing medical providers to choose nephrology as a specialty because there is currently a shortage of nephrologists in the US. Furthermore, support from other health professionals such as nurses, home aides, dialysis administrators, patient educators, and dietitians is paramount to a successful transition toward increased home dialysis.^87,122

Home dialysis in pandemic situations

The recent worldwide coronavirus disease 2019 (COVID-19) pandemic has further highlighted the drawbacks of IHD and the potential benefits of home dialysis. COVID-19 severity and mortality are increased in populations with certain risk factors, including older age, diabetes, and hypertension.^123,124 Many patients with ESKD have 1 or more of these risk factors and often also have an impaired immune system.^125,126 Indeed, patients with ESKD appear to have contracted COVID-19 at high rates, with case series from HD centers in China¹²⁶ and Italy^127,128 showing 15%−16% of their patients test positive. Of laboratory-confirmed COVID-19-positive patients who were reported to the Centers for Disease Control and Prevention, 71% of patients with known CKD were hospitalized.¹²⁹

Several organizations have suggested protocols to minimize the transmission of COVID-19 at dialysis centers that include temperature screening, use of personal protective equipment, hand washing, isolation of symptomatic patients in a separate room, and observance of other social distancing and disinfection measures. Home dialysis would effectively reduce the exposure of dialysis patients.

Concerns have been raised about shortages of in-patient kidney replacement therapy and trained staff, especially because 20%−40% of COVID-19 patients in the general population develop acute kidney injury and thus require dialysis.^130,131 Some physicians have suggested lowering the number of IHD sessions to twice weekly during this time, which would reduce the exposure time of both patients and staff and also conserve dialysis supplies.^132,133 Others fear that twice-weekly IHD could result in increased health risks and ultimately greater health care resource utilization.¹³⁴

Especially during times of crisis such as the COVID-19 pandemic, transitioning patients to home dialysis would relieve strain on medical facilities and comply with social distancing. However, this would necessitate the prioritization of procedures for vascular access or peritoneal catheter placement in addition to the time required for patient and caregiver training.^135,136 For both incident and continuing home dialysis patients, it is recommended that routine clinic visits be replaced by telehealth during the pandemic.^136,137 Overall, the COVID-19 outbreak may result in lasting changes in dialysis modalities and patient care, perhaps with a transition toward greater utilization of home dialysis.¹³⁸

Kidney Transplantation in ESKD

The last aim of the AAKH focuses on kidney transplantation, a key component of kidney replacement therapy in patients with ESKD.^8,139 Over 75,000 patients in the US are on the kidney transplant waiting list, but only 21,000 transplants are performed per year.² The cost per person per year for kidney transplantation ($35,817) is 2–3 times less than for PD or HD.² Fewer than one-third of kidneys transplanted in the US are from living donors,² so projects to develop artificial kidneys are underway¹⁴⁰ as are efforts to reform the kidney donation process.⁸

Post-transplantation anemia is prevalent in patients receiving a kidney transplant, affecting nearly 20%–51% of patients, particularly within the first 6 months after transplant surgery, and may arise due to iron deficiency, reduced allograft function, immunosuppression from medication, or infection.¹⁴¹ Early post-transplantation anemia is associated with graft loss and amplified risk of mortality with higher risk as anemia severity increases.¹⁴¹ Current guidelines for the management of post-transplantation anemia follow the general treatment guidelines for anemia of patients with CKD; however, clinical trial data supporting these recommendations in transplant recipients are sparse.⁵ A randomized clinical trial comparing the effect of epoetin beta to attain normalized (13.0–15.0 g/dl) versus lower Hb values (10.5–11.5 g/dl) in transplant recipients showed a slower progression of allograft nephropathy, and a significant improvement in QOL in the target Hb ≥13.0 g/dl group,¹⁴² but further studies with a larger cohort are warranted, given the increase in cardiovascular events or stroke reported in the CHOIR and TREAT trials after ESA therapy to achieve higher Hb levels in patients with CKD who were not on dialysis and had not received a previous kidney transplant.¹⁴³ A retrospective cohort study from a transplant registry showed a significant increase in mortality associated with ESA therapy targeting Hb >14.0 g/dl in kidney transplant recipients.¹⁴⁴ The clinical advantages of new therapies to treat anemia in transplant recipients undergoing immunosuppressive therapy and possible cotreatment of comorbid diseases remain to be seen.

Conclusions

Kidney disease and kidney failure are public health concerns, and a collaborative effort from health care and dialysis providers as well as patients and caregivers is required to address the unmet needs of patients with CKD or ESKD and to overcome barriers that prevent these patients from accessing the benefits of home dialysis. The AAKH is placing an emphasis on home dialysis modalities in order to provide better care for patients with ESKD and to reduce associated costs of a growing ESKD patient population.

In terms of flexible scheduling, home dialysis proves superior to IHD, and associated patient out-of-pocket costs may be outweighed by increased schedule flexibility and compatibility with employment. Potential improvements in or equivalence to IHD for all-cause mortality, hypertension, left ventricular mass, hospitalizations, and QOL have all been reported in patients undergoing home dialysis. Anemia management for patients using home dialysis can be streamlined with the use of the new, orally administered HIF-PH inhibitors. Improvements in technique (e.g., with videodialysis training or assisted care) may decrease the burden of infection risk over time, particularly in PD. Although at-home dialysis may not be a viable option for all patients with ESKD (e.g., older patients with certain comorbidities or cognitive issues), the AAKH and its associated new policy directives encourage widespread use of home dialysis modalities that aim to significantly improve kidney health in the US while reducing the cost of care.

Disclosures

EVL reports being a subinvestigator for Research by Design (Chicago, IL) and has received grants from ZS Pharma outside of the submitted work. AR reports grants and personal fees from AstraZeneca and personal fees from Relypsa outside of the submitted work.