Home-Based Dialysis: A Primer for the Internist.

Home-based dialysis modalities offer both clinical and practical advantages to patients. The use of the home-based modalities, peritoneal dialysis and home hemodialysis, has been increasing over the past decade after a long period of decline. Given the increasing frequency of use of these types of dialysis, it is important for clinicians to be familiar with how these types of dialysis are performed and key clinical aspects of care related to their use in patients with end-stage kidney disease.

The coronavirus disease 2019 pandemic: the disruptor that maintenance dialysis never anticipated.

PURPOSE OF REVIEW: The novel coronavirus 2019 (COVID-19) pandemic has upended maintenance dialysis in the United States. I review changes in prevalence, incidence, mortality, and other clinical outcomes among patients undergoing dialysis since March 2020, highlighting vulnerabilities in the current system and opportunities for improved care in the future. RECENT FINDINGS: The number of dialysis patients in the United States declined between March 2020 and March 2021, an unprecedented year-over-year drop in the census. Some of the decline can be attributed to an early drop in patients initiating dialysis but most of the decline can be attributed to excess mortality. Kidney transplants also declined during the early part of the pandemic. Home dialysis utilization increased during 2020 but that increase was largely in line with secular trends. The rate of hospitalization for causes other than COVID-19 fell significantly during 2020. SUMMARY: The epidemiology of dialysis in the United States is clearly modifiable, as it reflects decisions to initiate treatment, prescribe home therapies, and hospitalize patients with acute medical needs. On the other hand, some outcomes are powerfully guided by health outcomes in the general population, thus limiting the ability of dialysis providers and nephrologists to influence outcomes.

Apixaban Dosing Patterns Versus Warfarin in Patients With Nonvalvular Atrial Fibrillation Receiving Dialysis: A Retrospective Cohort Study.

BACKGROUND & OBJECTIVES: Comparison of clinical outcomes across anticoagulation regimens using different apixaban dosing or warfarin is not well-defined in patients with nonvalvular atrial fibrillation (AF) who are receiving dialysis. This study compared these outcomes in a US national cohort of patients with kidney failure receiving maintenance dialysis. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Patients receiving dialysis represented in the US Renal Data System database 2013-2018 who had AF and were treated with apixaban or warfarin. EXPOSURE: First prescribed treatment with apixaban dosed according to the label, apixaban dosed below the label, or warfarin. OUTCOME: Ischemic stroke/systemic embolism, major bleeding, and all-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards models with inverse probability of treatment weighting. Analyses simulating an intention-to-treat (ITT) approach as well as those incorporating censoring at drug switch or discontinuation (CAS) were also implemented. Inverse probability of censoring weighting was used to account for possible informative censoring. RESULTS: Among 17,156 individuals, there was no difference in risk of stroke/systemic embolism among the label-concordant apixaban, below-label apixaban, and warfarin treatment groups. Both label-concordant (HR, 0.67 [95% CI, 0.55-0.81]) and below-label (HR, 0.68 [95% CI, 0.55-0.84]) apixaban dosing were associated with a lower risk of major bleeding compared with warfarin in ITT analyses. Compared with label-concordant apixaban, below-label apixaban was not associated with a lower bleeding risk (HR, 1.02 [95% CI, 0.78-1.34]). In the ITT analysis of mortality, label-concordant apixaban dosing was associated with a lower risk versus warfarin (HR, 0.85 [95% CI, 0.78-0.92]) while there was no significant difference in mortality between below-label dosing of apixaban and warfarin (HR, 0.97 [95% CI, 0.89-1.05]). Overall, results were similar for the CAS analyses. LIMITATIONS: Study limited to US Medicare beneficiaries; reliance on administrative claims to ascertain outcomes of AF, stroke, and bleeding; likely residual confounding. CONCLUSIONS: Among patients with nonvalvular AF undergoing dialysis, warfarin is associated with an increased risk of bleeding compared with apixaban. The risk of bleeding with below-label apixaban was not detectably less than with label-concordant dosing. Label-concordant apixaban dosing is associated with a mortality benefit compared to warfarin. Label-concordant dosing, rather than reduced-label dosing, may offer the most favorable benefit-risk trade-off for dialysis patients with nonvalvular AF.

Initial Effects of COVID-19 on Patients with ESKD.

BACKGROUND: Reports from around the world have indicated a fatality rate of patients with coronavirus disease 2019 (COVID-19) in the range of 20%-30% among patients with ESKD. Population-level effects of COVID-19 on patients with ESKD in the United States are uncertain. METHODS: We identified patients with ESKD from Centers for Medicare and Medicaid Services data during epidemiologic weeks 3-27 of 2017-2020 and corresponding weeks of 2017-2019, stratifying them by kidney replacement therapy. Outcomes comprised hospitalization for COVID-19, all-cause death, and hospitalization for reasons other than COVID-19. We estimated adjusted relative rates (ARRs) of death and non-COVID-19 hospitalization during epidemiologic weeks 13-27 of 2020 (March 22 to July 4) versus corresponding weeks in 2017-2019. RESULTS: Among patients on dialysis, the rate of COVID-19 hospitalization peaked between March 22 and April 25 2020. Non-Hispanic Black race and Hispanic ethnicity associated with higher rates of COVID-19 hospitalization, whereas peritoneal dialysis was associated with lower rates. During weeks 13-27, ARRs of death in 2020 versus 2017-2019 were 1.17 (95% confidence interval [95% CI], 1.16 to 1.19) and 1.30 (95% CI, 1.24 to 1.36) among patients undergoing dialysis or with a functioning transplant, respectively. Excess mortality was higher among non-Hispanic Black, Hispanic, and Asian patients. Among patients on dialysis, the rate of non-COVID-19 hospitalization during weeks 13-27 in 2020 was 17% lower versus hospitalization rates for corresponding weeks in 2017-2019. CONCLUSIONS: During the first half of 2020, the clinical outcomes of patients with ESKD were greatly affected by COVID-19, and racial and ethnic disparities were apparent. These findings should be considered in prioritizing administration of COVID-19 vaccination.

Changes in Treatment of Patients with Incident ESKD during the Novel Coronavirus Disease 2019 Pandemic.

BACKGROUND: The COVID-19 pandemic caused major disruptions to care for patients with advanced CKD. METHODS: We investigated the incidence of documented ESKD, ESKD treatment modalities, changes in eGFR at dialysis initiation, and use of incident central venous catheters (CVCs) by epidemiologic week during the first half of 2020 compared with 2017-2019 historical trends, using Centers for Medicare and Medicaid Services data. We used Poisson and logistic regression for analyses of incidence and binary outcomes, respectively. RESULTS: Incidence of documented ESKD dropped dramatically in 2020 compared with the expected incidence, particularly during epidemiologic weeks 15-18 (April, incidence rate ratio [IRR], 0.75; 95% CI, 0.73 to 0.78). The decrease was most pronounced for individuals aged ≥75 years (IRR, 0.69; 95% CI, 0.66 to 0.73). Pre-emptive kidney transplantation decreased markedly during weeks 15-18 (IRR, 0.56; 95% CI, 0.46 to 0.67). Mean eGFR at dialysis initiation decreased by 0.33 ml/min per 1.73 m2 in weeks 19-22; non-Hispanic Black patients exhibited the largest decrease, at 0.61 ml/min per 1.73 m2. The odds of initiating dialysis with eGFR <10 ml/min per 1.73 m2 were highest during weeks 19-22 (May, OR, 1.14; 95% CI, 1.05 to 1.17), corresponding to an absolute increase of 2.9%. The odds of initiating peritoneal dialysis (versus hemodialysis) were 24% higher (OR, 1.24; 95% CI, 1.14 to 1.34) in weeks 11-14, an absolute increase of 2.3%. Initiation with a CVC increased by 3.3% (OR, 1.30; 95% CI, 1.20 to 1.41). CONCLUSIONS: During the first wave of the COVID-19 pandemic, the number of patients starting treatment for ESKD fell to a level not observed since 2011. Changes in documented ESKD incidence and other aspects of ESKD-related care may reflect differential access to care early in the pandemic.

Funding Innovative Dialysis Technology in the United States: Home Dialysis and the ESRD Transitional Add-on Payment for New and Innovative Equipment and Supplies (TPNIES).

Innovative, patient-centered, and pragmatic dialysis technologies are urgently needed to accommodate the growing national interest in home dialysis use. To help achieve this goal, the US Centers for Medicare & Medicaid Services (CMS) are expanding reimbursement for eligible home dialysis machines through an existing payment mechanism, the transitional add-on payment for new and innovative equipment and supplies (TPNIES). This mechanism incentivizes the early adoption of innovative equipment into practice by reimbursing dialysis providers up to 26% of the total cost of approved home dialysis machines. Machines are evaluated for TPNIES eligibility using prespecified substantial clinical improvement (SCI) criteria that are derived from the Inpatient Prospective Payment System (for non-nephrology technologies). Although the SCI criteria may be suitable for some non-nephrology technologies, they have not been adapted to consider the unique and complex care inherent in home dialysis. Thus, many of the SCI criteria appear unsuitable for home dialysis machines. To better incentivize innovation, CMS should develop nephrology-specific transparent and pragmatic criteria for TPNIES. In this perspective, we provide an overview of the TPNIES payment mechanism, highlight areas of concern within the policy, and offer solutions for improving TPNIES that could better promote the adoption of new home dialysis machines.

Contemporary Trends in Clinical Outcomes among Dialysis Patients with Medicare Coverage.

BACKGROUND: The dialysis patient population in the United States continues to grow. Trends in rates of death and hospitalization among dialysis patients have important consequences for outpatient dialysis capacity and Medicare spending. OBJECTIVES: To estimate contemporary trends in rates of death and hospitalization among dialysis patients in the United States, overall and within subgroups. METHODS: We used Medicare Limited Data Sets (100% sample) in 2014-2017 to estimate trends in rates of death and hospitalization among dialysis patients with Medicare Parts A and B enrollment. We used seasonal autoregressive integrated moving average models to identify secular trends in the incidence of outcomes. RESULTS: There were 631,075 unique patients; 222,924 deaths; and 1,876,779 hospital admissions. Weekly risks of both death and hospitalization exhibited strong seasonality. However, overall weekly risks of death were 34.9, 35.4, 35.2, and 35.7 deaths per 10,000 patients in 2014-2017, respectively (p = 0.47, from a likelihood ratio test of secular trend). The overall weekly risk of hospitalization was 3.08, 3.05, 3.11, and 3.11% in 2014, 2015, 2016, and 2017, respectively (p = 0.30). There were significant secular trends in risk of death in subgroups defined by black race and residency in South Atlantic states (p < 0.05). There were also secular trends in risk of hospitalization in subgroups defined by age 20-44 years, concurrent enrollment in Medicaid, and residency in South Central states. CONCLUSION: For the first time since the beginning of this century, rates of both death and hospitalization among dialysis patients with Medicare fee-for-service coverage have stagnated. The reasons for this change are unknown and require detailed assessment. Persistent lack of change in clinical outcomes may alter the future expectations about dialysis patient population growth.

Effect of dialysate potassium and lactate on serum potassium and bicarbonate concentrations during daily hemodialysis at low dialysate flow rates.

BACKGROUND: Observational studies of hemodialysis patients treated thrice weekly have shown that serum and dialysate potassium and bicarbonate concentrations are associated with patient outcomes. The effect of more frequent hemodialysis on serum potassium and bicarbonate concentrations has rarely been studied, especially for treatments at low dialysate flow rate. METHODS: These post-hoc analyses evaluated data from patients who transferred from in-center hemodialysis (HD) to daily HD at low dialysate flow rates during the FREEDOM Study. The primary outcomes were the change in predialysis serum potassium and bicarbonate concentrations after transfer from in-center HD (mean during the last 3 months) to daily HD (mean during the first 3 months). RESULTS: After transfer from in-center HD to daily HD (data from 345 patients, 51 ± 15 years of age, mean ± standard deviation), predialysis serum potassium decreased (P < 0.001) by approximately 0.4 mEq/L when dialysate potassium concentration during daily HD was 1 mEq/L; no change occurred when dialysate potassium concentration during daily HD was 2 mEq/L. After transfer from in-center HD to daily HD (data from 284 patients, 51 ± 15 years of age), predialysis serum bicarbonate concentration decreased (P = 0.0022) by 1.0 ± 3.3 mEq/L when dialysate lactate concentration was 40 mEq/L but increased (P < 0.001) by 2.5 ± 3.5 mEq/L when dialysate lactate concentration was 45 mEq/L. These relationships were dependent on serum potassium and bicarbonate concentrations during in-center HD. CONCLUSIONS: Control of serum potassium and bicarbonate concentrations during daily HD at low dialysate flow rates is readily achievable; the choice of dialysate potassium and lactate concentration can be informed when transfer is from in-center HD to daily HD.

Phosphate-Binder Use in US Dialysis Patients: Prevalence, Costs, Evidence, and Policies.

Medicare costs for phosphate binders for US dialysis patients and patients with chronic kidney disease enrolled in Medicare Part D exceeded $1.5 billion in 2015. Previous data have shown that Part D costs for mineral and bone disorder medications increased faster than costs for all Part D medications for dialysis patients. Despite extensive use of phosphate binders and escalating costs, conclusive evidence is lacking that they improve important clinical end points in dialysis patients or non-dialysis-dependent patients with chronic kidney disease. Using dialysis patient data from the US Renal Data System and laboratory information from the Centers for Medicare & Medicaid Services (CMS) CROWNWeb data, we update information on trends in phosphate-binder use, calcium and phosphorus values, and costs for Medicare-covered dialysis patients. We discuss these results in the context of evidence from clinical trials, meta-analyses, and observational studies evaluating phosphate-binder efficacy, safety, comparative effectiveness, and cost-effectiveness. Based on our analysis, we note a need for US Food and Drug Administration guidance regarding clinical evaluation of new phosphate binders, and we suggest that it would be in CMS' best interest to fund a clinical trial to assess whether lower versus higher phosphate concentrations improve hard clinical outcomes, and if so, whether particular phosphate binders are superior to placebo or other binders in improving these outcomes.

Drug Therapy Problem Severity Following Hospitalization and Association With 30-Day Clinical Outcomes.

BACKGROUND: Improved understanding of how drug therapy problems (DTPs) contribute to rehospitalization is needed. OBJECTIVE: The primary objectives were to assess the association of DTP likelihood of harm (LoH) severity score, as measured by comprehensive medication management (CMM) pharmacist after hospital discharge, with 30-day risk of hospital readmission, observation visit, or emergency department visit, and to determine whether resolution of DTPs reduces 30-day risk. Secondary objectives were to determine if any eventswere associated with DTPs and preventability of events. METHODS: Data were collected for 365 patients who received CMM following hospitalization and had at least 1 DTP identified. Retrospective chart reviews were completed for 80 patients with subsequent events to assess associationg with a DTP and its preventability. RESULTS: For each 1-point increment in maximum LoH score, there was 10% higher risk of the composite end point (hazard ratio [HR]=1.10; 95% CI:0.97-1.26; P=0.13). When DTPs were resolved by the CMM pharmacist, the association was attenuated, with a HR of 1.15 (95% CI:0.96-1.38; P=0.12) when the DTP was unresolved and HR of 1.09 (95% CI:0.96-1.25; P=0.52) when resolved; for hospital readmission alone, the corresponding HRs were 1.23 (95% CI:1.00-1.53; P=0.05) and 1.05 (95% CI:0.87-1.27; P=0.60). Of 80 subsequent events, 44 were associated with a medication; 22 were considered preventable. Conclusion and Relevance: The LoH severity score was associated with risk of 30-day events. The strength of association was attenuated when DTPs were resolved by the CMM pharmacist. However, because of statistical uncertainty, larger studies are needed to confirm these patterns.

Mortality, Hospitalization, and Technique Failure in Daily Home Hemodialysis and Matched Peritoneal Dialysis Patients: A Matched Cohort Study.

BACKGROUND: Use of home dialysis is growing in the United States, but few direct comparisons of major clinical outcomes on daily home hemodialysis (HHD) versus peritoneal dialysis (PD) exist. STUDY DESIGN: Matched cohort study. SETTING & PARTICIPANTS: We matched 4,201 new HHD patients in 2007 to 2010 with 4,201 new PD patients from the US Renal Data System database. PREDICTOR: Daily HHD versus PD. OUTCOMES: Relative mortality, hospitalization, and technique failure. RESULTS: Mean time from end-stage renal disease onset to home dialysis therapy initiation was 44.6 months for HHD and 44.3 months for PD patients. In intention-to-treat analysis, HHD was associated with 20% lower risk for all-cause mortality (HR, 0.80; 95% CI, 0.73-0.87), 8% lower risk for all-cause hospitalization (HR, 0.92; 95% CI, 0.89-0.95), and 37% lower risk for technique failure (HR, 0.63; 95% CI, 0.58-0.68), all relative to PD. In the subset of 1,368 patients who initiated home dialysis therapy within 6 months of end-stage renal disease onset, HHD was associated with similar risk for all-cause mortality (HR, 0.95; 95% CI, 0.80-1.13), similar risk for all-cause hospitalization (HR, 0.96; 95% CI, 0.88-1.05), and 30% lower risk for technique failure (HR, 0.70; 95% CI, 0.60-0.82). Regarding hospitalization, risk comparisons favored HHD for cardiovascular disease and dialysis access infection and PD for bloodstream infection. LIMITATIONS: Matching unlikely to reduce confounding attributable to unmeasured factors, including residual kidney function; lack of data regarding dialysis frequency, duration, and dose in daily HHD patients and frequency and solution in PD patients; diagnosis codes used to classify admissions. CONCLUSIONS: These data suggest that relative to PD, daily HHD is associated with decreased mortality, hospitalization, and technique failure. However, risks for mortality and hospitalization were similar with these modalities in new dialysis patients. The interaction between modality and end-stage renal disease duration at home dialysis therapy initiation should be investigated further.

Intensive Hemodialysis, Mineral and Bone Disorder, and Phosphate Binder Use.

Mineral and bone disorder is a common complication of end-stage renal disease. Notably, hyperphosphatemia likely promotes calcification of the myocardium, valves, and arteries. Hyperphosphatemia is associated with higher risk for cardiovascular mortality and morbidity along a gradient beginning at 5.0mg/dL. Among contemporary hemodialysis (HD) patients, mean serum phosphorus level is 5.2mg/dL, although 25% of patients have serum phosphorus levels of 5.5 to 6.9mg/dL; and 13%, >7.0mg/dL. Treatment of hyperphosphatemia is burdensome. Dialysis patients consume a mean of 19 pills per day, half of which are phosphate binders. Medicare Part D expenditures on binders for dialysis patients approached $700 million in 2013. Phosphorus removal with thrice-weekly HD (4 hours per session) is ∼3,000mg/wk. However, clearance is unlikely to counterbalance dietary intake, which varies around a mean of 7,000mg/wk. Dietary restriction and phosphate binders are important interventions, but each has limitations. Dietary control is complicated by limited access to healthy food choices and unclear labeling. Meanwhile, adherence to phosphate binders is poor, especially in younger patients and those with high pill burden. Multiple randomized clinical trials show that intensive HD reduces serum phosphorus levels. In the Frequent Hemodialysis Network (FHN) trial, short daily and nocturnal schedules reduced serum phosphorus levels by 0.6 and 1.6mg/dL, respectively, relative to 3 sessions per week. A similar effect of nocturnal HD was observed in an earlier trial. In the daily arm of the FHN trial, intensive HD significantly lowered estimated phosphate binder dose per day, whereas in the nocturnal arm, intensive HD led to binder discontinuation in 75% of patients. However, intensive HD appears to have no meaningful effects on serum calcium and parathyroid hormone concentrations. In conclusion, intensive HD, especially nocturnal HD, lowers serum phosphorus levels and decreases the need for phosphate binders.

Intensive Hemodialysis, Blood Pressure, and Antihypertensive Medication Use.

Hypertension is a cardinal feature of end-stage renal disease (ESRD). Hypertensive nephropathy is the primary cause of ESRD for nearly 30% of patients, and the prevalence of hypertension is >85% in new patients with ESRD. In contemporary hemodialysis (HD) patients, mean predialysis systolic blood pressure (SBP) is nearly 150mmHg, and about 70%, 50%, and 40% use ß-blockers, calcium channel blockers, and renin-angiotensin system inhibitors, respectively. Predialysis SBP generally exhibits a U-shaped association with mortality risk. Interdialytic ambulatory SBP is more strongly associated with risk. Hypertension is multifactorial; key causes include persistent hypervolemia and elevated peripheral resistance. With 3 HD sessions per week, blood pressure (BP) climbs during the interdialytic interval, in step with interdialytic weight gain, particularly among elderly patients and those with higher dry weight. Elevated peripheral resistance can be attributed to inappropriate activation of the sympathetic nervous system due to higher plasma norepinephrine concentrations. Multiple randomized clinical trials show that intensive HD reduces BP and the need for oral medications indicated for hypertension. In the first 2 months of the Frequent Hemodialysis Network trial, the short daily schedule reduced predialysis SBP by 7.7mmHg, whereas the nocturnal schedule reduced predialysis SBP by 7.3mmHg, both relative to 3 sessions per week. Improvements were sustained after 12 months. Both schedules reduced antihypertensive medication use relative to 3 sessions per week. In FREEDOM (Following Rehabilitation, Economics, and Everyday-Dialysis Outcome Measurements), a prospective cohort study of short daily HD, the mean number of prescribed antihypertensive agents decreased from 1.7 to 1.0 in 1 year, whereas the percentage of patients not prescribed antihypertensive agents increased from 21% to 47%. Nocturnal HD appears to markedly reduce total peripheral resistance and plasma norepinephrine and restore endothelium-dependent vasodilation. In conclusion, intensive HD reduces BP and the need for antihypertensive medications.

Intensive Hemodialysis and Health-Related Quality of Life.

Diminished health-related quality of life (HRQoL) is common in dialysis patients and associated with increased risks for morbidity and mortality. Patients may present limitations in both physical and mental HRQoL. Poor physical HRQoL may be defined by limited physical function, role limitations due to physical health, dissatisfaction with physical ability, and impaired mobility. Sleep disorders such as obstructive sleep apnea, restless legs, and fatigue are typical manifestations of poor physical HRQoL in dialysis patients. Poor mental HRQoL may be defined by depressive thinking, lack of positive affect, anxiety, and feelings of social isolation. The prevalence of depression is high in dialysis patients. Intensive hemodialysis (HD) can positively address HRQoL. In 3 randomized clinical trials, relative to conventional HD, intensive HD increased physical and mental component summary scores from the 36-Item Short-Form Health Survey (SF-36), although individual treatment effects of daily nocturnal HD were not statistically significant. In another large prospective study, initiation of short daily HD therapy was followed after 12 months by improvements in all SF-36 domains, sleep quality, and restless legs symptoms. In a small study of nocturnal HD, apnea and hypopnea episodes per hour decreased by almost 70% after conversion from conventional HD. Intensive HD is also associated with a large reduction in postdialysis recovery time. In contrast, 2 randomized clinical trials failed to demonstrate statistically significant effects of intensive HD on the Beck Depression Inventory score despite a significant decrease in Beck Depression Inventory score in the prospective study of short daily HD. Furthermore, intensive HD may not improve objective physical performance and can increase burden on caregivers in the home setting. In conclusion, intensive HD potentially can address both physical and mental aspects of poor HRQoL relative to conventional HD. However, more studies are needed to understand the effects of intensive HD, including specific schedules, on HRQoL.