Individualized anemia management enhanced by ferric pyrophosphate citrate protocol.

The optimal use of erythropoiesis-stimulating agents (ESAs) and parenteral iron in managing anemia in end-stage renal disease (ESRD) remains controversial. One-size-fits-all rule-based algorithms dominate dosing protocols for ESA and parenteral iron. However, the Food & Drug Administration (FDA) guidelines for using ESAs in chronic kidney disease recommend individualized therapy for the patient. This prospective quality assurance project was at a single hemodialysis (HD) center comprising three 6-month phases (A, B, C) separated by 3-month washout periods. Standard bi-weekly ESA dose titration and intravenous (IV) iron sucrose protocols were used in baseline Phase A, and ferric pyrophosphate citrate (FPC) augmented iron in Phase B. In Phase C, an FPC protocol and weekly, individualized ESA management were used. We examined clinic-level mean differences in hemoglobin (Hb) and ESRD-related outcomes by phase with repeated ANOVA. To examine the Hb at the patient level, we used multi-level mixed-effect regression adjusting for phase, month, and other relevant confounders at each month over time to derive the mean marginal effects of phase. There were 54, 78, and 66 patients in phases A, B, and C, respectively, with raw mean Hb values of 9.9, 10.2, and 10.3 g/dL. The percentage of Hb values < 9 g/dL declined from 14.3% in Phase A to 7.6% in Phase C (p = 0.007). The multivariable mixed-effect regression results showed mean marginal Hb was higher by 0.3 mg/dL and 0.4 mg/dL in Phases B and C, respectively, compared to Phase A. We also observed reduced ferritin (p = 0.003) and transferrin saturation (TSAT) (p = 0.008) levels from Phase A to Phase C with the repeated ANOVA analysis. Ferric pyrophosphate citrate (FPC) appears to support more efficient ESA-stimulated erythropoiesis. Moreover, individualized ESA management combined with FPC (Phase C) was associated with further improvement in efficiency as we observed the fewest patients with Hb values < 9 g/dL concurrent with greater decreases in ferritin levels and reduced ESA doses. However, future prospective studies to confirm these findings on a larger, more diverse cohort of ESRD patients are warranted.

Real-world assessment: effectiveness and safety of extended-release calcifediol and other vitamin D therapies for secondary hyperparathyroidism in CKD patients.

INTRODUCTION: Extended-release calcifediol (ERC), active vitamin D hormones and analogs (AVD) and nutritional vitamin D (NVD) are commonly used therapies for treating secondary hyperparathyroidism (SHPT) in adults with stage 3-4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI). Their effectiveness for increasing serum total 25-hydroxyvitamin D (25D) and reducing elevated plasma parathyroid hormone (PTH), the latter of which is associated with increased morbidity and mortality, has varied across controlled clinical trials. This study aimed to assess real-world experience of ERC and other vitamin D therapies in reducing PTH and increasing 25D. METHODS: Medical records of 376 adult patients with stage 3-4 CKD and a history of SHPT and VDI from 15 United States (US) nephrology clinics were reviewed for up to 1 year pre- and post-ERC, NVD or AVD initiation. Key study variables included patient demographics, concomitant usage of medications and laboratory data. The mean age of the study population was 69.5 years, with gender and racial distributions representative of the US CKD population. Enrolled patients were grouped by treatment into three cohorts: ERC (n = 174), AVD (n = 55) and NVD (n = 147), and mean baseline levels were similar for serum 25D (18.8-23.5 ng/mL), calcium (Ca: 9.1-9.3 mg/dL), phosphorus (P: 3.7-3.8 mg/dL) and estimated glomerular filtration rate (eGFR: 30.3-35.7 mL/min/1.73m2). Mean baseline PTH was 181.4 pg/mL for the ERC cohort versus 156.9 for the AVD cohort and 134.8 pg/mL (p < 0.001) for the NVD cohort. Mean follow-up during treatment ranged from 20.0 to 28.8 weeks. RESULTS: Serum 25D rose in all cohorts (p < 0.001) during treatment. ERC yielded the highest increase (p < 0.001) of 23.7 ± 1.6 ng/mL versus 9.7 ± 1.5 and 5.5 ± 1.3 ng/mL for NVD and AVD, respectively. PTH declined with ERC treatment by 34.1 ± 6.6 pg/mL (p < 0.001) but remained unchanged in the other two cohorts. Serum Ca increased 0.2 ± 0.1 pg/mL (p < 0.001) with AVD but remained otherwise stable. Serum alkaline phosphatase remained unchanged. CONCLUSIONS: Real-world clinical effectiveness and safety varied across the therapies under investigation, but only ERC effectively raised mean 25D (to well above 30 ng/mL) and reduced mean PTH levels without causing hypercalcemia.

Safety and Effectiveness of Difelikefalin in Patients With Moderate-to-Severe Pruritus Undergoing Hemodialysis: An Open-Label, Multicenter Study.

Rationale & Objective: Individuals with chronic kidney disease frequently suffer from chronic kidney disease-associated pruritus (CKD-aP), impacting sleep quality and quality of life (QoL) and increasing the likelihood of depression. Difelikefalin is a kappa-opioid receptor agonist recently approved in the United States for the treatment of moderate-to-severe CKD-aP in hemodialysis patients. Study 3105 was conducted to further assess the safety of difelikefalin and the effects on pruritus and QoL. Study Design: Open-label, multicenter, single-arm intervention trial. Setting & Participants: Maintenance hemodialysis patients with moderate-to-severe CKD-aP at enrollment. Intervention: Intravenous difelikefalin 0.5 µg/kg after each hemodialysis session for 12 weeks. Outcomes: The primary outcome was safety of difelikefalin. Secondary outcomes included: effectiveness of reducing itch intensity, assessed by the Worst Itching Intensity Numerical Rating Scale (WI-NRS); improving itch-related QoL, assessed with 5-D itch and Skindex-10 scales; and improvement of sleep, assessed with the Sleep Quality Numerial Rating Scale. Clinically meaningful thresholds for improvement in itch and QoL were previously established in this population. Results: Among 222 participants with baseline WI-NRS ≥5, mean [standard deviation] WI-NRS was 7.6 [1.3], mean age 58 years, 55% were male, and mean dialysis duration was 5.9 years; 197 participants (89%) completed treatment. Treatment-related treatment-emergent adverse events were reported in 16 participants (7.2%); those most commonly reported were somnolence (1.8%), hypoesthesia (1.4%), nausea (0.9%), and dizziness (0.9%). No deaths or serious treatment-emergent adverse events were considered treatment-related. Clinically meaningful reduction in itch intensity (≥3-point improvement) was reported by 74% of participants, with 70% and 63% also reporting a clinically relevant improvement in QoL as measured by 5-D itch and Skindex-10. Sleep quality improvement (≥3-point reduction on the Numerical Rating Scale) was reported in 66% of participants. Limitations: No placebo control group. Conclusions: Difelikefalin was well tolerated, and treatment was associated with clinically meaningful improvements in itch intensity and itch-related QoL measures as well as improvements in sleep quality among individuals receiving hemodialysis who had moderate-to-severe CKD-aP, providing important insights into expected real-world effectiveness. Funding: Cara Therapeutics. Trial Registration: NCT03998163.

Implementing Advance Care Planning for dialysis patients: HIGHway project.

BACKGROUND: Patients undergoing hemodialysis have a high mortality rate and yet underutilize palliative care and hospice resources. The Shared Decision Making-Renal Supportive Care (SDM-RSC) intervention focused on goals of care conversations between patients and family members with the nephrologist and social worker. The intervention targeted deficiencies in communication, estimating prognosis, and transition planning for seriously ill dialysis patients. The intervention showed capacity to increase substantially completion of advance care directives. The HIGHway Project, adapted from the previous SDM-RSC, scale up training social workers or nurses in dialysis center in advance care planning (ACP), and then support them for a subsequent 9-month action period, to engage in ACP conversations with patients at their dialysis center regarding their preferences for end-of-life care. METHODS: We will train between 50-60 dialysis teams, led by social workers or nurses, to engage in ACP conversations with patients at their dialysis center regarding their preferences for end-of-life care. This implementation project uses the Knowledge to Action (KTA) Framework within the Consolidated Framework for Implementation Research (CFIR) to increase adoption and sustainability in the participating dialysis centers. This includes a curriculum about how to hold ACP conversation and coaching with monthly teleconferences through case discussion and mentoring. An application software will guide on the process and provide resources for holding ACP conversations. Our project will focus on implementation outcomes. Success will be determined by adoption and effective use of the ACP approach. Patient and provider outcomes will be measured by the number of ACP conversations held and documented; the quality and fidelity of ACP conversations to the HIGHway process as taught during education sessions; impact on knowledge and skills; content, relevance, and significance of ACP intervention for patients, and Supportive Kidney Care (SKC) App usage. Currently HIGHway is in the recruitment stage. DISCUSSION: Effective changes to advance care planning processes in dialysis centers can lead to institutional policy and protocol changes, providing a model for patients receiving dialysis treatment in the US. The result will be a widespread improvement in advance care planning, thereby remedying one of the current barriers to patient-centered, goal-concordant care for dialysis patients. TRIAL REGISTRATION: The George Washington University Protocol Record NCR213481, Honoring Individual Goals and Hopes: Implementing Advance Care Planning for Persons with Kidney Disease on Dialysis, is registered in ClinicalTrials.gov Identifier: NCT05324878 on April 11th, 2022.

Video Images about Decisions for Ethical Outcomes in Kidney Disease (VIDEO-KD): the study protocol for a multi-centre randomised controlled trial.

INTRODUCTION: Older patients with advanced chronic kidney disease (CKD) often are inadequately prepared to make informed decisions about treatments including dialysis and cardiopulmonary resuscitation. Further, evidence shows that patients with advanced CKD do not commonly engage in advance care planning (ACP), may suffer from poor quality of life, and may be exposed to end-of-life care that is not concordant with their goals. We aim to study the effectiveness of a video intervention on ACP, treatment preferences and other patient-reported outcomes. METHODS AND ANALYSIS: The Video Images about Decisions for Ethical Outcomes in Kidney Disease trial is a multi-centre randomised controlled trial that will test the effectiveness of an intervention that includes a CKD-related video decision aid followed by recording personal video declarations about goals of care and treatment preferences in older adults with advancing CKD. We aim to enrol 600 patients over 5 years at 10 sites. ETHICS AND DISSEMINATION: Regulatory and ethical aspects of this trial include a single Institutional Review Board mechanism for approval, data use agreements among sites, and a Data Safety and Monitoring Board. We intend to disseminate findings at national meetings and publish our results. TRIAL REGISTRATION NUMBER: NCT04347629.

Real-World Assessment: Clinical Effectiveness and Safety of Extended-Release Calcifediol.

INTRODUCTION: The safety and efficacy of extended-release calcifediol (ERC) as a treatment for secondary hyperparathyroidism (SHPT) in adults with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI) has been demonstrated in prospective randomized clinical trials (RCTs). ERC (Rayaldee®) was approved by the Food and Drug Administration in 2016 on the basis of these prospective RCTs. The current retrospective study assessed the postlaunch data available with respect to ERC's efficacy and safety in increasing serum 25-hydroxyvitamin D (25D) and reducing parathyroid hormone (PTH) in the indicated population. MATERIALS AND METHODS: Medical records of 174 patients who met study criteria from 15 geographically representative United States nephrology clinics were reviewed for 1 year before and after initiation of ERC treatment. Enrolled subjects had ages ≥18 years, stage 3 or 4 CKD, and a history of SHPT and VDI. Key study variables included patient demographics, medication usage, and laboratory results, including serial 25D and PTH determinations. RESULTS: The enrolled subjects had a mean age of 69.0 years, gender and racial distributions representative of the indicated population, and were balanced for CKD stage. Most (98%) received 30 mcg of ERC/day during the course of treatment (mean follow-up: 24 weeks). Baseline 25D and PTH levels averaged 20.3 ± 0.7 (standard error) ng/mL and 181 ± 7.4 pg/mL, respectively. ERC treatment raised 25D by 23.7 ± 1.6 ng/mL (p < 0.001) and decreased PTH by 34.1 ± 6.6 pg/mL (p < 0.001) with nominal changes of 0.1 mg/dL (p > 0.05) in serum calcium (Ca) and phosphorus (P) levels. DISCUSSION/CONCLUSION: Analysis of postlaunch data confirmed ERC's effectiveness in increasing serum 25D and reducing PTH levels without statistically significant or notable impact on serum Ca and P levels. A significant percentage of these subjects achieved 25D levels ≥30 mg/mL and PTH levels which decreased by at least 30% from baseline. Dose titration to 60 mcgs was rarely prescribed. Closer patient monitoring and appropriate dose titration may have led to a higher percentage of subjects achieving an increase in 25D levels to at least 50 ng/mL and a reduction in PTH levels of at least 30%.

Assessing accuracy of estimated dry weight in dialysis patients post transplantation: the kidney knows best.

INTRODUCTION: Estimated dry weight is used to guide fluid removal during outpatient hemodialysis sessions. Errors in estimated dry weight can result in intradialytic hypotension and interdialytic fluid overload. The goal of this study was to assess the accuracy of estimated dry weight by comparing it to the 2-week post-transplant weight in two cohorts of hemodialysis patients. METHODS: This observational, multi-center, retrospective cohort study included maintenance hemodialysis patients who underwent kidney transplantation at two medical centers in Massachusetts. The relationship between estimated dry weight pre-transplant and weight at week 2 post-transplant in patients with good allograft function (serum creatinine ≤ 1.5 mg/dL) was analyzed. Estimated dry weight was considered accurate if it was within ± 2% of the week 2 post-transplant weight. RESULTS: Fifty seven patients with good allograft function were identified: mean age 54 ± 14 years, 32 (58%) from deceased donors, 22 (38.6%) females. 38 were Caucasian (66.7%), 11 Hispanic (19.3%), 3 black (5.3%), and 5 others (8.8%). 2-week mean post transplantation serum creatinine was 1.2 ± 0.2 mg/dL. Mean (SD) estimated dry weight was 71.4 ± 15.9. Before transplantation, only 14 (24.6%) patients were within ± 2% of the 2-week post-transplant weight; 23 (40.3%) were above and 20 (35.1%) were below. CONCLUSIONS: Our point of view, based on the assumption that the weight of patients with good allograft function at 2 weeks post-transplant approaches their accurate dry weight, is that a majority of maintenance hemodialysis patients (75.4%) are hypervolemic or hypovolemic prior to renal transplantation. This highlights the importance of finding novel tools to achieve euvolemia in patients undertaking dialysis. Timely feedback regarding achieved weight 2 weeks post-transplant to treating nephrologists and dialysis centers may be a starting point for assessing accuracy of dry weight.

Winter roost selection of Lasiurine tree bats in a pyric landscape.

Day-roost selection by Lasiurine tree bats during winter and their response to dormant season fires is unknown in the southeastern United States where dormant season burning is widely applied. Although fires historically were predominantly growing season, they now occur in the dormant season in this part of the Coastal Plain to support a myriad of stewardship activities, including habitat management for game species. To examine the response of bats to landscape condition and the application of prescribed fire, in the winter of 2019, we mist-netted and affixed radio-transmitters to 16 Lasiurine bats, primarily Seminole bats (Lasiurus seminolus) at Camp Blanding Joint Training Center in northern Florida. We then located day-roost sites to describe roost attributes. For five Seminole bats, one eastern red bat (Lasiurus borealis), and one hoary bat (Lasiurus cinereus), we applied prescribed burns in the roost area to observe bat response in real-time. Generally, Seminole bats selected day-roosts in mesic forest stands with high mean fire return intervals. At the roost tree scale, Seminole day-roosts tended to be larger, taller and in higher canopy dominance classes than surrounding trees. Seminole bats roosted in longleaf (Pinus palustris), slash (Pinus elliotii) and loblolly pine (Pinus taeda) more than expected based on availability, whereas sweetbay (Magnolia virginiana), water oak (Quercus nigra) and turkey oak (Quercus laevis), were roosted in less than expected based on availability. Of the seven roosts subjected to prescribed burns, only one male Seminole bat and one male eastern red bat evacuated during or immediately following burning. In both cases, these bats had day-roosted at heights lower than the majority of other day-roosts observed during our study. Our results suggest Seminole bats choose winter day-roosts that both maximize solar exposure and minimize risks associated with fire. Nonetheless, because selected day-roosts largely were fire-dependent or tolerant tree species, application of fire does need to periodically occur to promote recruitment and retention of suitable roost sites.

Clinical management of chronic kidney disease-associated pruritus: current treatment options and future approaches.

Chronic kidney disease (CKD)-associated pruritus (CKD-aP) is an underdiagnosed yet severely distressing condition that impacts 60% of patients on dialysis and many nondialysis patients with Stages 3-5 CKD. However, despite its high prevalence, there are currently limited treatment options available for these patients and a lack of treatment guidelines for clinicians. In this manuscript, we reviewed the available literature in order to evaluate the current management and treatment options for CKD-aP, including dialysis management, topical treatments, gabapentinoids, opioids and alternative medicine. We also review the available data on CKD-aP treatments in development and propose new guidelines for managing patients with CKD-aP.

The Role of Feedback Control Design in Developing Anemia Management Protocols.

The optimal use of erythropoiesis stimulating agents to treat anemia of end-stage renal disease remains difficult due to reported associations with adverse events. A patient's hemoglobin response to these agents cannot be accurately described using population-level models due to many individual factors including chronic inflammation, red blood cell lifespan, and acute blood loss. As a consequence, it is generally understood that current one-size-fits-all anemia management protocols result in suboptimal outcomes. In this paper, we report on our collaboration with the medical community in designing anemia management protocols. In clinical implementation, these new dosing protocols have led to improved outcomes due to their use of control-relevant modelling, model parameter identification, and principles of feedback control. This is an example of medical professionals and control engineers working together to positively affect the performance of anemia management protocols in end-stage renal disease.

Publisher Correction: COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The effects of 16-weeks of prebiotic supplementation and aerobic exercise training on inflammatory markers, oxidative stress, uremic toxins, and the microbiota in pre-dialysis kidney patients: a randomized controlled trial-protocol paper.

BACKGROUND: Chronic kidney disease (CKD) is characterized by dysbiosis, elevated levels of uremic toxins, systemic inflammation, and increased markers of oxidative stress. These factors lead to an increased risk of cardiovascular disease (CVD) which is common among CKD patients. Supplementation with high amylose maize resistant starch type 2 (RS-2) can change the composition of the gut microbiota, and reduce markers of inflammation and oxidative stress in patients with end-stage renal disease. However, the impact of RS-2 supplementation has not been extensively studied in CKD patients not on dialysis. Aerobic exercise training lowers certain markers of inflammation in CKD patients. Whether combining aerobic training along with RS-2 supplementation has an additive effect on the aforementioned biomarkers in predialysis CKD patients has not been previously investigated. METHODS: The study is being conducted as a 16-week, double-blind, placebo controlled, parallel arm, randomized controlled trial. Sixty stage 3-4 CKD patients (ages of 30-75 years) are being randomized to one of four groups: RS-2 & usual care, RS-2 & aerobic exercise, placebo (cornstarch) & usual care and placebo & exercise. Patients attend four testing sessions: Two baseline (BL) sessions with follow up visits 8 (wk8) and 16 weeks (wk16) later. Fasting blood samples, resting brachial and central blood pressures, and arterial stiffness are collected at BL, wk8 and wk16. A stool sample is collected for analysis of microbial composition and peak oxygen uptake is assessed at BL and wk16. Blood samples will be assayed for p-cresyl sulphate and indoxyl sulphate, c-reactive protein, tumor necrosis factor α, interleukin 6, interleukin 10, monocyte chemoattractant protein 1, malondialdehyde, 8-isoprostanes F2a, endothelin-1 and nitrate/nitrite. Following BL, subjects are randomized to their group. Individuals randomized to conditions involving exercise will attend three supervised moderate intensity (55-65% peak oxygen uptake) aerobic training sessions (treadmills, bikes or elliptical machine) per week for 16 weeks. DISCUSSION: This study has the potential to yield information about the effect of RS-2 supplementation on key biomarkers believed to impact upon the development of CVD in patients with CKD. We are examining whether there is an additive effect of exercise training and RS-2 supplementation on these key variables. TRIAL REGISTRATION: Clinicaltrials.gov Trial registration# NCT03689569 . 9/28/2018, retrospectively registered.

COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup.

Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional 'surges' in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI.

Validation of a Core Patient-Reported Outcome Measure for Fatigue in Patients Receiving Hemodialysis: The SONG-HD Fatigue Instrument.

BACKGROUND AND OBJECTIVES: Fatigue is a very common and debilitating symptom and identified by patients as a critically important core outcome to be included in all trials involving patients receiving hemodialysis. A valid, standardized measure for fatigue is needed to yield meaningful and relevant evidence about this outcome. This study validated a core patient-reported outcome measure for fatigue in hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A longitudinal cohort study was conducted to assess the validity and reliability of a new fatigue measure (Standardized Outcomes in Nephrology-Hemodialysis Fatigue [SONG-HD Fatigue]). Eligible and consenting patients completed the measure at three time points: baseline, a week later, and 12 days following the second time point. Cronbach α and intraclass correlation coefficient were calculated to assess internal consistency, and Spearman rho was used to assess convergent validity. Confirmatory factor analysis was also conducted. Hemodialysis units in the United Kingdom, Australia, and Romania participated in this study. Adult patients aged 18 years and over who were English speaking and receiving maintenance hemodialysis were eligible to participate. Standardized Outcomes in Nephrology-Hemodialysis, the Visual Analog Scale for fatigue, the 12-Item Short Form Survey, and Functional Assessment of Chronic Illness Therapy-Fatigue were used. RESULTS: In total, 485 participants completed the study across the United Kingdom, Australia, and Romania. Psychometric assessment demonstrated that Standardized Outcomes in Nephrology-Hemodialysis is internally consistent (Cronbach α =0.81-0.86) and stable over a 1-week period (intraclass correlation coefficient =0.68-0.74). The measure demonstrated convergence with Functional Assessment of Chronic Illness Therapy-Fatigue and had moderate correlations with other measures that assessed related but not the same concept (the 12-Item Short Form Survey and the Visual Analog Scale). Confirmatory factor analysis supported the one-factor model. CONCLUSIONS: SONG-HD Fatigue seems to be a reliable and valid measure to be used in trials involving patients receiving hemodialysis.

Impact of Dietary Potassium Restrictions in CKD on Clinical Outcomes: Benefits of a Plant-Based Diet.

In patients with advanced-stage chronic kidney disease (CKD), progressive kidney function decline leads to increased risk for hyperkalemia (serum potassium > 5.0 or >5.5 mEq/L). Medications such as renin-angiotensin-aldosterone system inhibitors pose an additional hyperkalemia risk, especially in patients with CKD. When hyperkalemia develops, clinicians often recommend a diet that is lower in potassium content. This review discusses the barriers to adherence to a low-potassium diet and the impact of dietary restrictions on adverse clinical outcomes. Accumulating evidence indicates that a diet that incorporates potassium-rich foods has multiple health benefits, which may also be attributable to the other vitamin, mineral, and fiber content of potassium-rich foods. These benefits include blood pressure reductions and reduced risks for cardiovascular disease and stroke. High-potassium foods may also prevent CKD progression and reduce mortality risk in patients with CKD. Adjunctive treatment with the newer potassium-binding agents, patiromer and sodium zirconium cyclosilicate, may allow for optimal renin-angiotensin-aldosterone system inhibitor therapy in patients with CKD and hyperkalemia, potentially making it possible for patients with CKD and hyperkalemia to liberalize their diet. This may allow them the health benefits of a high-potassium diet without the increased risk for hyperkalemia, although further studies are needed.

Use of a Supportive Kidney Care Video Decision Aid in Older Patients: A Randomized Controlled Trial.

BACKGROUND: There are few studies of patient-facing decision aids that include supportive kidney care as an option. We tested the efficacy of a video decision aid on knowledge of supportive kidney care among older patients with advanced CKD. METHODS: Participants (age ≥ 65 years with advanced CKD) were randomized to receive verbal or video education. Primary outcome was knowledge of supportive kidney care (score range 0-3). Secondary outcomes included preference for supportive kidney care, and satisfaction and acceptability of the video. RESULTS: Among all participants (n = 100), knowledge of supportive kidney care increased significantly after receiving education (p < 0.01); however, there was no difference between study arms (p = 0.68). There was no difference in preference for supportive kidney care between study arms (p = 0.49). In adjusted analyses, total health literacy score (aOR 1.08 [95% CI: 1.003-1.165]) and nephrologists' answer of "No" to the Surprise Question (aOR 4.87 [95% CI: 1.22-19.43]) were associated with preference for supportive kidney care. Most felt comfortable watching the video (96%), felt the content was helpful (96%), and would recommend the video to others (96%). CONCLUSIONS: Among older patients with advanced CKD, we did not detect a significant difference between an educational verbal script and a video decision aid in improving knowledge of supportive kidney care or preferences. However, patients who received video education reported high satisfaction and acceptability ratings. Future research will determine the effectiveness of a supportive kidney care video decision aid on real-world patient outcomes. TRIAL REGISTRATION: NCT02698722 (ClinicalTrials.gov).

Randomized Controlled Trial of Difelikefalin for Chronic Pruritus in Hemodialysis Patients.

INTRODUCTION: There is an unmet medical need for pruritus associated with chronic kidney disease, a distressing complication characterized by generalized and persistent itch affecting 20% to 40% of patients undergoing hemodialysis. Here we report the results of a phase 2 trial evaluating the efficacy and safety of a novel peripherally restricted kappa opioid receptor agonist, difelikefalin, in adult patients undergoing hemodialysis with pruritus. METHODS: In this study, 174 hemodialysis patients with moderate-to-severe pruritus were randomly assigned to receive difelikefalin (0.5, 1.0, or 1.5 µg/kg) or placebo intravenously thrice weekly after each hemodialysis session for 8 weeks in a double-blind, controlled trial. The primary endpoint was the change from baseline at week 8 in the weekly mean of the 24-hour Worst Itching Intensity Numerical Rating Scale score. The secondary efficacy endpoint was the change in itch-related quality of life measured by the Skindex-10 questionnaire. Other endpoints included safety, sleep quality, and additional measures including the 5-D itch scale. RESULTS: A significant reduction from baseline in itch intensity scores at week 8 favored all difelikefalin doses combined versus placebo (P = 0.002). Difelikefalin also showed improvement over placebo in Skindex-10, 5-D itch, and sleep disturbance scores (P ≤ 0.005). Overall, 78% of patients receiving difelikefalin reported treatment-emergent adverse events versus 42% of patients given placebo, with diarrhea, dizziness, nausea, somnolence, and fall being the most frequent (≥5%). CONCLUSION: In this trial, difelikefalin effectively reduced itching intensity and improved sleep and itch-related quality of life.

Symptoms of Secondary Hyperparathyroidism in Patients Receiving Maintenance Hemodialysis: A Prospective Cohort Study.

RATIONALE & OBJECTIVE: Although multiple lines of evidence suggest a negative impact of secondary hyperparathyroidism on patients with kidney failure treated by hemodialysis, it is uncertain whether patients can detect associated symptoms. The objective was to determine whether changes in parathyroid hormone (PTH) levels are associated with changes in symptoms within this patient population. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: 165 adults with hyperparathyroidism secondary to kidney failure diagnosed, a range of dialysis vintages, and receiving regular hemodialysis from a US single-provider organization. EXPOSURE: Change in PTH levels over 24 weeks. OUTCOMES: 19 putative symptoms of secondary hyperparathyroidism measured up to 4 times using a self-administered questionnaire that assessed severity on a 5-level ordinal scale. ANALYTICAL APPROACH: Longitudinal associations between changes in PTH levels and symptom severity were assessed using generalized additive models. RESULTS: The 165 participants studied represented 81% of enrollees (N=204) who had sufficiently complete data for analysis. Mean age was 56 years and 54% were women. Increases in PTH levels over time were associated (P<0.1) with worsening of bone aches and stiffness, joint aches, muscle soreness, overall pain, itchy skin, and tiredness, and the effects were more pronounced with larger changes in PTH levels. LIMITATIONS: Findings may have been influenced by confounding by unmeasured comorbid conditions, concomitant medications, and multiple testing coupled with a P value threshold of 0.10. CONCLUSIONS: In this exploratory study, we observed that among patients with secondary hyperparathyroidism, increases in PTH levels over time were associated with worsening of 1 or more cluster of symptoms. Replication of these findings in other populations is needed before concluding about the magnitude and shape of these associations. If replicated, these findings could inform clinically useful approaches for measuring patient-reported outcomes related to secondary hyperparathyroidism.

Advance care planning with patients on hemodialysis: an implementation study.

BACKGROUND: Patients with end-stage kidney disease (ESKD) on hemodialysis have limited life expectancy, yet their palliative care needs often go unmet. The aim of this study was to identify barriers and facilitators for implementation of "Shared Decision Making and Renal Supportive Care" (SDM-RSC), an intervention to improve advance care planning (ACP) for patients with ESKD on hemodialysis. METHODS: The Consolidated Framework for Implementation Research (CFIR) was the organizing framework for this study. CFIR is a theory-based implementation framework consisting of five domains (Intervention Characteristics, Inner Setting, Outer Setting, Characteristics of Individuals, and Process), each of which has associated constructs. Potential barriers and facilitators to implementation of the SDM-RSC intervention were identified through observation of study procedures, surveys of social workers nephrologists, study participants, and family members, and assessment of intervention fidelity. RESULTS: Twenty-nine nephrologists and 24 social workers, representing 18 outpatient dialysis units in Massachusetts (n = 10) and New Mexico (n = 8), were trained to conduct SDM-RSC intervention sessions. A total of 102 of 125 patient enrolled in the study received the intervention; 40 had family members present. Potential barriers and facilitators to implementation of the SDM-RSC intervention were identified in each of the five CFIR domains. Barriers included complexity of the intervention; challenges to meeting with patients on non-dialysis days; difficulties scheduling intervention sessions due to nephrologists' and social workers' caseloads; perceived need for local policy change regarding ACP; perceived need for additional ACP training for social workers and nephrologists; and lack of endorsement of the intervention by some staff members. Facilitators included: training for social workers, national dialysis chain leadership engagement and the institution of social worker/nephrologist clinic champions. CONCLUSIONS: ACP for patients on hemodialysis can have a positive impact on end-of-life outcomes for patients and their families but does not take place routinely. The barriers to effective implementation of interventions to improve ACP identified in this study might be addressed by: adapting the intervention for local contexts with input from clinicians, dialysis staff, patients and families; providing nephrologists and social workers additional training prior to delivering the intervention; and developing policy that routinizes ACP for hemodialysis patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT02405312. Registered 04/01/2015.