Comparative Effectiveness of mRNA-based BNT162b2 Vaccine versus Adenovirus Vector-Based Ad26.COV2.S Vaccine for the Prevention of COVID-19 among Dialysis Patients.

BACKGROUND: Studies have demonstrated that mRNA-based SARS-CoV-2 vaccines are highly effective among patients on dialysis. Because individual vaccines may be differentially available or acceptable to patients, it is important to understand comparative effectiveness relative to other vaccines, such those on the basis of adenovirus technologies. METHODS: In this retrospective study, we compared the clinical effectiveness of adenovirus vector-based Ad26.COV2.S (Janssen/Johnson & Johnson) to mRNA-based BNT162b2 (Pfizer/BioNTech) in a contemporary cohort of patients on dialysis. Patients who received a first BNT162b2 dose were matched 1:1 to Ad26.COV2.S recipients on the basis of date of first vaccine receipt, US state of residence, site of dialysis care (in-center versus home), history of COVID-19, and propensity score. The primary outcome was the comparative rate of COVID-19 diagnoses starting in the 7th week postvaccination. In a subset of consented patients who received Ad26.COV2.S, blood samples were collected ≥28 days after vaccination and anti-SARS-CoV-2 immunoglobulin G antibodies were measured. RESULTS: A total of 2572 matched pairs of patients qualified for analysis. Cumulative incidence rates of COVID-19 did not differ for BNT162b2 versus Ad26.COV2.S. No differences were observed in peri-COVID-19 hospitalizations and deaths among patients receiving BNT162b2 versus Ad26.COV2.S, who were diagnosed with COVID-19 during the at-risk period. Results were similar when excluding patients with a history of COVID-19, in subgroup analyses restricted to patients who completed the two-dose BNT162b2 regimen, and in patients receiving in-center hemodialysis. SARS-CoV-2 antibodies were detected in 59.4% of 244 patients who received Ad26.COV2.S. CONCLUSIONS: In a large real-world cohort of patients on dialysis, no difference was detected in clinical effectiveness of BNT162b2 and Ad26.COV2.S over the first 6 months postvaccination, despite an inconsistent antibody response to the latter.

Real-World Effectiveness and Immunogenicity of BNT162b2 and mRNA-1273 SARS-CoV-2 Vaccines in Patients on Hemodialysis.

BACKGROUND: Patients on hemodialysis have an elevated risk for COVID-19 but were not included in efficacy trials of SARS-CoV-2 vaccines. METHODS: We conducted a retrospective, observational study to estimate the real-world effectiveness and immunogenicity of two mRNA SARS-CoV-2 vaccines in a large, representative population of adult hemodialysis patients in the United States. In separate, parallel analyses, patients who began a vaccination series with BNT162b2 or mRNA-1273 in January and February 2021 were matched with unvaccinated patients and risk for outcomes were compared for days 1-21, 22-42, and ≥43 after first dose. In a subset of consented patients, blood samples were collected approximately 28 days after the second dose and anti-SARS-CoV-2 immunoglobulin G was measured. RESULTS: A total of 12,169 patients received the BNT162b2 vaccine (matched with 44,377 unvaccinated controls); 23,037 patients received the mRNA-1273 vaccine (matched with 63,243 unvaccinated controls). Compared with controls, vaccinated patients' risk of being diagnosed with COVID-19 postvaccination became progressively lower during the study period (hazard ratio and 95% confidence interval for BNT162b2 was 0.21 [0.13, 0.35] and for mRNA-1273 was 0.27 [0.17, 0.42] for days ≥43). After a COVID-19 diagnosis, vaccinated patients were significantly less likely than unvaccinated patients to be hospitalized (for BNT162b2, 28.0% versus 43.4%; for mRNA-1273, 37.2% versus 45.6%) and significantly less likely to die (for BNT162b2, 4.0% versus 12.1%; for mRNA-1273, 5.6% versus 14.5%). Antibodies were detected in 98.1% (309/315) and 96.0% (308/321) of BNT162b2 and mRNA-1273 patients, respectively. CONCLUSIONS: In patients on hemodialysis, vaccination with BNT162b2 or mRNA-1273 was associated with a lower risk of COVID-19 diagnosis and lower risk of hospitalization or death among those diagnosed with COVID-19. SARS-CoV-2 antibodies were detected in nearly all patients after vaccination. These findings support the use of these vaccines in this population.

"A Study in Yellow": Investigations in the Stereoselectivity of Ene-Reductases.

Ene-reductases from the Old Yellow Enzyme (OYE) superfamily are a well-known and efficient biocatalytic alternative for the asymmetric reduction of C=C bonds. Considering the broad variety of substituents that can be tolerated, and the excellent stereoselectivities achieved, it is apparent why these enzymes are so appealing for preparative and industrial applications. Different classes of C=C bonds activated by at least one electron-withdrawing group have been shown to be accepted by these versatile biocatalysts in the last decades, affording a vast range of chiral intermediates employed in the synthesis of pharmaceuticals, agrochemicals, flavours, fragrances and fine chemicals. In order to access both enantiomers of reduced products, stereodivergent pairs of OYEs are desirable, but their natural occurrence is limited. The detailed knowledge of the stereochemical course of the reaction can uncover alternative strategies to orient the selectivity via mutagenesis, evolution, and substrate engineering. An overview of the ongoing studies on OYE-mediated bioreductions will be provided, with particular focus on stereochemical investigations by deuterium labelling.

Antibody Status, Disease History, and Incidence of SARS-CoV-2 Infection Among Patients on Chronic Dialysis.

BACKGROUND: Although reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rare among individuals with few coronavirus disease 2019 (COVID-19) risk factors, the ability of naturally acquired immunity to prevent reinfection among patients with ESKD is not known. METHODS: This prospective study was conducted among adults with ESKD treated with in-center hemodialysis (ICHD) in the United States. Exposure was ascribed on the basis of the presence or absence of IgG against SARS-CoV-2 at baseline, and separately, a history of documented COVID-19 before study entry. Outcomes were assessed after an infection-free period, and were any SARS-CoV-2 infection (i.e., detected by protocolized PCR tests or during routine clinical surveillance), and clinically manifest COVID-19 (consisting of only the latter). RESULTS: Of 2337 consented participants who met study inclusion criteria, 9.5% were anti-SARS-CoV-2 IgG positive at baseline; 3.6% had a history of COVID-19. Over 6679 patient-months of follow-up, 263 participants had evidence of any SARS-CoV-2 infection, including 141 who had clinically manifest COVID-19. Presence of anti-SARS-CoV-2 IgG (versus its absence) at baseline was associated with lower risk of any SARS-CoV-2 infection (incidence rate ratio, 0.55; 95% confidence interval, 0.32 to 0.95) and clinically manifest COVID-19 0.21 (95% confidence interval, 0.07 to 0.67). CONCLUSION: Among patients with ESKD, naturally acquired anti-SARS-CoV-2 IgG positivity is associated with a 45% lower risk of subsequent SARS-CoV-2 infection, and a 79% lower risk of clinically manifest COVID-19. Because natural immunity is incomplete, patients with ESKD should be prioritized for SARS-CoV-2 vaccination, independent of their COVID-19 disease history.

International variation in dialysis discontinuation in patients with advanced kidney disease.

BACKGROUND: Decisions about dialysis for advanced kidney disease are often strongly shaped by sociocultural and system-level factors rather than the priorities and values of individual patients. We examined international variation in the uptake of conservative approaches to the care of patients with advanced kidney disease, in particular discontinuation of dialysis. METHODS: We employed an observational cohort study design using data collected from patients maintained on long-term hemodialysis between 1996 and 2015 in facilities across 12 developed countries participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS). The main outcome was discontinuation of dialysis therapy. We analyzed the association between several patient characteristics and time to dialysis discontinuation by country and phase of study entry. RESULTS: A total of 259 343 DOPPS patients contributed data to the study, of whom 48 519 (18.7%) died during the study period. Of the decedents, 5808 (12.0%) discontinued dialysis before death. Rates of discontinuation were higher within the first few months after initiation of dialysis, among older adults, among those with a greater number of comorbidities and among those living in an institution. After adjustment for age, sex, dialysis duration, diabetes and dialysis era, rates of discontinuation were highest in Canada, the United States and Australia/New Zealand (33.8, 31.4 and 21.5 per 1000/yr, respectively) and lowest in Japan and Italy (< 0.1 per 1000/yr). Crude discontinuation rates were highest in dialysis facilities that were more likely to offer comprehensive conservative renal care to older adults. INTERPRETATION: We found persistent international variation in average rates of dialysis discontinuation not explained by differences in patient case-mix. These differences may reflect physician-, facility- and society-level differences in clinical practice. There may be opportunities for international cross-collaboration to improve support for patients with end-stage renal disease who prefer a more conservative approach.

Conversion of Oleic Acid into Azelaic and Pelargonic Acid by a Chemo-Enzymatic Route.

A chemo-enzymatic approach for the conversion of oleic acid into azelaic and pelargonic acid is herein described. It represents a sustainable alternative to ozonolysis, currently employed at the industrial scale to perform the reaction. Azelaic acid is produced in high chemical purity in 44% isolation yield after three steps, avoiding column chromatography purifications. In the first step, the lipase-mediated generation of peroleic acid in the presence of 35% H2O2 is employed for the self-epoxidation of the unsaturated acid to the corresponding oxirane derivative. This intermediate is submitted to in situ acid-catalyzed opening, to afford 9,10-dihydroxystearic acid, which readily crystallizes from the reaction medium. The chemical oxidation of the diol derivative, using atmospheric oxygen as a stoichiometric oxidant with catalytic quantities of Fe(NO3)3∙9∙H2O, (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO), and NaCl, affords 9,10-dioxostearic acid which is cleaved by the action of 35% H2O2 in mild conditions, without requiring any catalyst, to give pelargonic and azelaic acid.

Use of a Decision Aid for Patients Considering Peritoneal Dialysis and In-Center Hemodialysis: A Randomized Controlled Trial.

RATIONALE & OBJECTIVE: Annually, about 100,000 US patients face the difficult choice between the most common dialysis types, in-center hemodialysis and peritoneal dialysis. This study evaluated the value of a new decision aid to assist in the choice of dialysis modality. STUDY DESIGN: A parallel-group randomized controlled trial to test the efficacy of the decision aid on decision-making outcomes. SETTING & PARTICIPANTS: English-speaking US adults with advanced chronic kidney disease and internet access enrolled in 2015. INTERVENTION: Participants randomly assigned to the decision aid intervention received information about chronic kidney disease, peritoneal dialysis, and hemodialysis and a value clarification exercise through the study website using their own electronic devices. Participants in the control arm were only required to complete the control questionnaire. Questionnaire responses were used to assess differences across arms in decision-making outcomes. OUTCOMES: Treatment preference, decisional conflict, decision self-efficacy, knowledge, and preparation for decision making. RESULTS: Of 234 consented participants, 94 (40.2%) were lost to follow-up before starting the study. Among the 140 (70 in each arm) who started the study, 7 were subsequently lost to follow-up. Decision aid users had lower decisional conflict scores (42.5 vs 29.1; P<0.001) and higher average knowledge scores (90.3 vs 76.5; P<0.001). Both arms had high decisional self-efficacy scores independent of decision aid use. Uncertainty about choice of dialysis treatment declined from 46% to 16% after using the decision aid. Almost all (>90%) users of the decision aid reported that it helped in decision making. LIMITATIONS: Limited generalizability from the study of self-selected study participants who had to have internet access, speak English, and have computer literacy. High postrandomization loss to follow-up. Evaluation of only short-term outcomes. CONCLUSIONS: The decision aid improves decision-making outcomes immediately after use. Implementation of the decision aid in clinical practice may allow further assessment of its effects on patient engagement and empowerment in choosing a dialysis modality. FUNDING: This study was funded through a Patient Centered Outcomes Research Institute (PCORI) award (#1109). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT02488317.

Palliative dialysis: Addressing the need for alternative dialysis delivery modes.

For some patients with kidney failure, particularly those who have limited life expectancy or severe comorbidities, the "standard" dialysis treatment regimen may be perceived as excessively burdensome and may not align well with the patient's own priorities. For such patients, a palliative approach to the provision of dialysis-whereby treatment is tailored to the needs of the individual so as to optimize quality of life and minimize disease-related symptoms, but limit treatment burden-might offer a way to better align the delivery of care with the life goals of the patient. Here, we discuss the fundamental principles of palliative dialysis: the patients who might most benefit from this approach, treatment strategies and considerations for implementation, as well as potential barriers to its provision.

Serum albumin and hospitalization among pediatric patients with end-stage renal disease who started dialysis therapy.

BACKGROUND: Hypoalbuminemia is a strong predictor of hospitalization and mortality among adult dialysis patients. However, data are scant on the association between serum albumin and hospitalization among children new to dialysis. METHODS: In a retrospective cohort study of children 1-17 years old with end-stage renal disease receiving dialysis therapy in a large US dialysis organization 2007-2011, we examined the association of serum albumin with hospitalization frequency and total hospitalization days using a negative binomial regression model. RESULTS: Among 416 eligible patients, median (interquartile range) age was 14 (10-16) years and mean ± SD baseline serum albumin level was 3.7 ± 0.8 g/dL. Two hundred sixty-six patients (64%) were hospitalized during follow-up with an incidence rate of 2.2 (95%CI, 1.9-2.4) admissions per patient-year. There was a U-shaped association between serum albumin and hospitalization frequency; hospitalization rates (95%CI) were 2.7 (2.2-3.2), 1.9 (1.5-2.4), 1.6 (1.3-1.9), and 2.7 (1.7-3.6) per patient-year among patients with serum albumin levels < 3.5, 3.5- < 4.0, 4.0- < 4.5, and ≥ 4.5 g/dL, respectively. Case mix-adjusted hospitalization incidence rate ratios (IRRs) (95%CI) were 1.63 (1.24-2.13), 1.32 (1.10-1.58), and 1.25 (1.06-1.49) at serum albumin levels 3.0, 3.5, and 4.5 g/dL, respectively (reference: 4.0 g/dL). Similar trends were observed in hospitalization days. These associations remained robust against further adjustment for laboratory variables associated with malnutrition and inflammation. CONCLUSIONS: Both high and low serum albumin were associated with higher hospitalization in children starting dialysis. Because the observed association is novel and not fully explainable especially for high serum albumin levels, interpreting the results requires caution and further studies are needed to confirm and elucidate this association before clinical recommendations are made.

Correction to: Use of the KDQOL-36™ for assessment of health-related quality of life among dialysis patients in the United States.

Following publication of the original article [1], the authors reported an error in Figs. 3 and S3.

Response to correspondence from Hays and colleagues concerning our paper entitled, use of the KDQOL-36™ for assessment of health-related quality of life among dialysis patients in the United States.

In their correspondence, Hays et al. raise two main critiques of our recently published article entitled "Use of the KDQOL-36™ for assessment of health-related quality of life among dialysis patients in the United States." First, Hays et al. expressed concerns regarding the comparison of mean scores on five Kidney Disease Quality of Life (KDQOL) subscales, given that the Physical Component Summary (PCS) and Mental Component Summary (MCS) are scored on a different numeric scale compared to the other three subscales. Second, Hays et al. note that the correlations reported in our manuscript between the general health perceptions item ("In general, would you say your health is excellent, very good, good, fair, or poor") and the 5 KDQOL subscales were inconsistent with findings derived from other KDQOL datasets. Here, we respond to these two critiques.

Use of the KDQOL-36™ for assessment of health-related quality of life among dialysis patients in the United States.

BACKGROUND: Health-related quality of life (HRQOL) is a key outcome for dialysis patients, and its assessment is mandated by the Centers for Medicaid and Medicare Services. The Kidney Disease Quality of Life (KDQOL-36™) survey is widely used for this assessment. KDQOL-36™ completion rates, and the distributions of scores and item responses, have not been examined in a large, nationally representative cohort of dialysis patients. METHODS: This retrospective, observational study considered 413,951 survey opportunities contributed by adult patients who received dialysis at a large dialysis organization in the United States during calendar years 2014, 2015, and 2016 and were not Veterans Affairs beneficiaries. RESULTS: During the study period, 240,343 unique patients completed a total of 330,412 surveys (overall completion rate 79.8%). Mean domain scores on the physical component summary (PCS), mental component summary (MCS), burden of kidney disease (BKD), symptoms and problems of kidney disease (SPKD), and effects of kidney disease (EKD) subscales were 36.6, 49.0, 51.3, 78.1, and 73.0, respectively. Scores were similar across dialysis modalities. Patient perceptions of general health were not correlated (R < 0.05) with PCS or SPKD. The SPKD showed ceiling effects: among patients treated with in-center hemodialysis, for all 12 items, < 10% of patients were "extremely bothered," while > 65% of patients reported being "not at all" or only "somewhat bothered;" for 3 items, > 85% of patients gave these latter two responses. Interdialytic weight gain was not correlated with patient-reported shortness of breath, PCS, or SPKD. CONCLUSIONS: Survey completion rates for the KDQOL-36™ were high, and scores were similar across dialysis modalities. Ceiling effects were observed for SPKD. Revision of the KDQOL-36™ to address factors that are most important to contemporary dialysis patients may be warranted.

Predictors of cinacalcet discontinuation and reinitiation in hemodialysis patients: results from 7 European countries.

BACKGROUND: The putative benefits of cinacalcet therapy for management of secondary hyperparathyroidism (SHPT) are thought to be most manifested when patients are taking it consistently and as prescribed. Real-world descriptions of cinacalcet prescription discontinuation and reinitiation in European hemodialysis patients are lacking. To address this knowledge gap, we used Dialysis Outcomes and Practice Patterns Study (DOPPS) data, based on dialysis facility medical records, from seven European countries to estimate rates and predictors of cinacalcet prescription discontinuation and reinitiation in hemodialysis patients and to describe the trajectories of CKD-MBD laboratory values after discontinuation. METHODS: Cox regression analyses were used to predict (1) cinacalcet discontinuation among 613 patients with ≥3 consecutive months without cinacalcet prescription immediately prior to a new cinacalcet prescription and (2) cinacalcet reinitiation among 415 patients with a newly discontinued cinacalcet prescription immediately after ≥3 consecutive months of prescribed use. RESULTS: Cinacalcet was discontinued in 21 and 35% of new users after 6 and 12 months, respectively. Cinacalcet was reinitiated in 38 and 49% of newly-discontinued users after 6 and 12 months, respectively. Predictors of discontinuation included lower parathyroid hormone (PTH) in the previous month (< 150 pg/ml vs. 150-299, HR = 2.57 [95% CI: 1.52-4.33]) and lower serum calcium in the previous month (< 8.4 mg/dl vs. 8.4-10.19, HR = 1.67 [95% CI: 1.08-2.59]). Predictors of reinitiation included higher PTH in the previous month (300-599 pg/ml vs. 150-299, HR = 1.88 [95% CI = 1.19-2.97]; 600+ pg/ml, HR = 3.02 [95% CI = 1.92-4.76]). After cinacalcet discontinuation, mean serum PTH increased from 408 to 510 pg/ml, mean serum calcium briefly rose from 9.12 to 9.22 mg/dl before declining to 9.06 mg/dl, and mean serum phosphorus showed little change. CONCLUSIONS: Nephrologist discontinuation of cinacalcet therapy is common in European countries. Additional research is needed to identify optimal cinacalcet treatment strategies for SHPT management, including comparisons of intermittent cinacalcet therapy versus sustained treatment with reduced dose or frequency.

DOPPS data suggest a possible survival benefit of renin angiotensin-aldosterone system inhibitors and other antihypertensive medications for hemodialysis patients.

The benefits of renin angiotensin-aldosterone system inhibitors (RAASi) are well-established in the general population, particularly among those with diabetes, congestive heart failure (CHF), or coronary artery disease (CAD). However, conflicting evidence from trials and concerns about hyperkalemia limit RAASi use in hemodialysis patients, relative to other antihypertensive agents, including beta blockers and calcium channel blockers. Therefore, we investigated prescription patterns and associations with mortality for RAASi and other antihypertensive agents using data from the international Dialysis Outcomes and Practice Patterns Study (DOPPS). Cox regression was used to estimate the effect of the prescription of RAASi and other antihypertensive agents at study entry on mortality in 11,421 incident (120 days or less) hemodialysis and 37,124 prevalent (over 120 days) hemodialysis patients from DOPPS phases 2-5 (2002-2015). Over 95% of RAASi were angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. RAASi prevalence was 39% and varied minimally by CHF and CAD. The adjusted hazard ratio for RAASi (vs. no RAASi) was 0.89 (95% confidence interval 0.80-0.99) among incident and 0.94 (0.90-0.99) among prevalent hemodialysis patients, with no convincing evidence of interaction with diabetes, CAD or CHF. Inverse associations with mortality were also observed for beta blockers and calcium channel blockers, and were stronger for angiotensin receptor blockers than angiotensin-converting enzyme inhibitors, but this latter finding requires further study. Thus, our observations suggest a relatively small survival benefit of RAASi and other antihypertensive agents in hemodialysis patients, though randomized prospective studies are needed to potentially change prescribing criteria.

International Differences in the Location and Use of Arteriovenous Accesses Created for Hemodialysis: Results From the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Vascular access practice is strongly associated with clinical outcomes. There is substantial international variation in the use of arteriovenous fistulas (AVFs) and grafts (AVGs), as well as AVF maturation time and location. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Hemodialysis patients participating in the prospective Dialysis Outcomes and Practice Patterns Study (DOPPS) from the United States, Japan, and Europe/ANZ (Belgium, France, Germany, Italy, Spain, Sweden, United Kingdom, Australia, and New Zealand), including 3,850 patients receiving 4,247 new AVFs and 842 patients receiving 1,129 new AVGs in 2009 to 2015. AVF location trends were based on 38,868 AVFs recorded in DOPPS 1 to 5 cross-sections (1996-2015). PREDICTORS: Demographics, comorbid conditions, dialysis vintage, body mass index, facility percentage AVF use, median blood flow rate, and AVF location. OUTCOMES: AVF location; successful AVF/AVG use (≥30 days of continuous use); time-to-first successful AVF/AVG use (maturation). RESULTS: During DOPPS 1 to 5, the percentage of AVFs created in the lower arm was consistently ≥93% in Japan and 65% to 77% in Europe/ANZ, but in the United States, this value declined from 70% (DOPPS 1) to 32% (DOPPS 5). Patient characteristics associated with AVF location differed by region. Successful AVF use was 87% in Japan, 67% in Europe/ANZ, and 64% in the United States, whereas successful AVG use was 86%, 75%, and 78%, respectively. Successful AVF use was greater for upper- versus lower-arm AVFs in the United States, with little difference in Europe/ANZ and the opposite pattern in Japan. Median time until first successful AVF use was 10 days in Japan, 46 days in Europe/ANZ, and 82 days in United States; until first successful AVG use: 6, 24, and 29 days, respectively. LIMITATIONS: Potential measurement error related to chart data abstraction in multiple hemodialysis facilities. CONCLUSIONS: Large international differences exist in AVF location, predictors of AVF location, successful use of AVFs, and time to first AVF/AVG use, challenging what constitutes best practice. The large US shift from lower- to upper-arm AVFs raises serious concerns about long-term health implications for some patients and how policies and practices aimed at increasing AVF use have affected AVF placement location.

Missed Hemodialysis Treatments: International Variation, Predictors, and Outcomes in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

RATIONALE & OBJECTIVE: Missed hemodialysis (HD) treatments not due to hospitalization have been associated with poor clinical outcomes and related in part to treatment nonadherence. Using data from the Dialysis Outcomes and Practice Patterns Study (DOPPS) phase 5 (2012-2015), we report findings from an international investigation of missed treatments among patients prescribed thrice-weekly HD. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: 8,501 patients participating in DOPPS, on HD therapy for more than 120 days, from 20 countries. Longitudinal and cross-sectional analyses were performed based on the 4,493 patients from countries in which 4-month missed treatment risk was > 5%. PREDICTORS: The main predictor of patient outcomes was 1 or more missed treatments in the 4 months before DOPPS phase 5 enrollment; predictors of missed treatments included country, patient characteristics, and clinical factors. OUTCOMES: Mortality, hospitalization, laboratory measures, patient-reported outcomes, and 4-month missed treatment risk. ANALYTICAL APPROACH: Outcomes were assessed using Cox proportional hazards, logistic, and linear regression, adjusting for case-mix and country. RESULTS: The 4-month missed treatment risk varied more than 50-fold across all 20 DOPPS countries, ranging from < 1% in Italy and Japan to 24% in the United States. Missed treatments were more likely with younger age, less time on dialysis therapy, shorter HD treatment time, lower Kt/V, longer travel time to HD centers, and more symptoms of depression. Missed treatments were positively associated with all-cause mortality (HR, 1.68; 95% CI, 1.37-2.05), cardiovascular mortality, sudden death/cardiac arrest, hospitalization, serum phosphorus level > 5.5mg/dL, parathyroid hormone level > 300pg/mL, hemoglobin level < 10g/dL, higher kidney disease burden, and worse general and mental health. LIMITATIONS: Possible residual confounding; temporal ambiguity in the cross-sectional analyses. CONCLUSIONS: In the countries with a 4-month missed treatment risk > 5%, HD patients were more likely to die, be hospitalized, and have poorer patient-reported outcomes and laboratory measures when 1 or more missed treatments occurred in a 4-month period. The large variation in missed treatments across 20 nations suggests that their occurrence is potentially modifiable, especially in the United States and other countries in which missed treatment risk is high.

Mortality risk in patients on hemodiafiltration versus hemodialysis: a 'real-world' comparison from the DOPPS.

Background: With its convective component, hemodiafiltration (HDF) provides better middle molecule clearance compared with hemodialysis (HD) and is postulated to improve survival. A previous analysis of Dialysis Outcomes and Practice Patterns Study (DOPPS) data in 1998-2001 found lower mortality rates for high replacement fluid volume HDF versus HD. Randomized controlled trials have not shown uniform survival advantage for HDF; in secondary (non-randomized) analyses, better outcomes were observed in patients receiving the highest convection volumes. Methods: In a 'real-world' setting, we analyzed patients on dialysis >90 days from seven European countries in DOPPS Phases 4 and 5 (2009-15). Adjusted Cox regression was used to study HDF (versus HD) and mortality, overall and by replacement fluid volume. Results: Among 8567 eligible patients, 2012 (23%) were on HDF, ranging from 42% in Sweden to 12% in Germany. Median follow-up was 1.5 years during which 1988 patients died. The adjusted mortality hazard ratio (95% confidence interval) was 1.14 (1.00-1.29) for any HDF versus HD and 1.08 (0.92-1.28) for HDF >20 L replacement fluid volume versus HD. Similar results were found for cardiovascular and infection-related mortality. In an additional analysis aiming to avoid treatment-by-indication bias, we did not observe lower mortality rates in facilities using more HDF (versus HD). Conclusions: Our results do not support the notion that HDF provides superior patient survival. Further trials designed to test the effect of high-volume HDF (versus lower volume HDF versus HD) on clinical outcomes are needed to adequately inform clinical practices.

Perceptions about the dialysis modality decision process among peritoneal dialysis and in-center hemodialysis patients.

BACKGROUND: Patients reaching end-stage renal disease must make a difficult decision regarding renal replacement therapy (RRT) options. Because the choice between dialysis modalities should include patient preferences, it is critical that patients are engaged in the dialysis modality decision. As part of the Empowering Patients on Choices for RRT (EPOCH-RRT) study, we assessed dialysis patients' perceptions of their dialysis modality decision-making process and the impact of their chosen modality on their lives. METHODS: A 39-question survey was developed in collaboration with a multi-stakeholder advisory panel to assess perceptions of patients on either peritoneal dialysis (PD) or in-center hemodialysis (HD). The survey was disseminated to participants in the large US cohorts of the Dialysis Outcomes and Practice Patterns Study (DOPPS) and the Peritoneal DOPPS (PDOPPS). Survey responses were compared between PD and in-center HD patients using descriptive statistics, adjusted logistic generalized estimating equation models, and linear mixed regression models. RESULTS: Six hundred fourteen PD and 1346 in-center HD participants responded. Compared with in-center HD participants, PD participants more frequently reported that they were engaged in the decision-making process, were provided enough information, understood differences between dialysis modalities, and felt satisfied with their modality choice. PD participants also reported more frequently than in-center HD participants that partners or spouses (79% vs. 70%), physician assistants (80% vs. 66%), and nursing staff (78% vs. 60%) had at least some involvement in the dialysis modality decision. Over 35% of PD and in-center HD participants did not know another dialysis patient at the time of their modality decision and over 60% did not know the disadvantages of their modality type. Participants using either dialysis modality perceived a moderate to high impact of dialysis on their lives. CONCLUSIONS: PD participants were more engaged in the modality decision process compared to in-center HD participants. For both modalities, there is room for improvement in patient education and other support for patients choosing a dialysis modality.

Interdialytic Weight Gain: Trends, Predictors, and Associated Outcomes in the International Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: High interdialytic weight gain (IDWG) is associated with adverse outcomes in hemodialysis (HD) patients. We identified temporal and regional trends in IDWG, predictors of IDWG, and associations of IDWG with clinical outcomes. STUDY DESIGN: Analysis 1: sequential cross-sections to identify facility- and patient-level predictors of IDWG and their temporal trends. Analysis 2: prospective cohort study to assess associations between IDWG and mortality and hospitalization risk. SETTING & PARTICIPANTS: 21,919 participants on HD therapy for 1 year or longer in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 2 to 5 (2002-2014). PREDICTORS: Analysis 1: study phase, patient demographics and comorbid conditions, HD facility practices. Analysis 2: relative IDWG, expressed as percentage of post-HD weight (<0%, 0%-0.99%, 1%-2.49%, 2.5%-3.99% [reference], 4%-5.69%, and ≥5.7%). OUTCOMES: Analysis 1: relative IDWG as a continuous variable using linear mixed models; analysis 2: mortality; all-cause and cause-specific hospitalization using Cox regression, adjusting for potential confounders. RESULTS: From phase 2 to 5, IDWG declined in the United States (-0.29kg; -0.5% of post-HD weight), Canada (-0.25kg; -0.8%), and Europe (-0.22kg; -0.5%), with more modest declines in Japan and Australia/New Zealand. Among modifiable factors associated with IDWG, the most notable was facility mean dialysate sodium concentration: every 1-mEq/L greater dialysate sodium concentration was associated with 0.13 (95% CI, 0.11-0.16) greater relative IDWG. Compared to relative IDWG of 2.5% to 3.99%, there was elevated risk for mortality with relative IDWG≥5.7% (adjusted HR, 1.23; 95% CI, 1.08-1.40) and elevated risk for fluid-overload hospitalization with relative IDWG≥4% (HRs of 1.28 [95% CI, 1.09-1.49] and 1.64 [95% CI, 1.27-2.13] for relative IDWGs of 4%-5.69% and ≥5.7%, respectively). LIMITATIONS: Possible residual confounding. No dietary salt intake data. CONCLUSIONS: Reductions in IDWG during the past decade were partially explained by reductions in dialysate sodium concentration. Focusing quality improvement strategies on reducing occurrences of high IDWG may improve outcomes in HD patients.

Dialysate Potassium, Serum Potassium, Mortality, and Arrhythmia Events in Hemodialysis: Results From the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Sudden death is a leading cause of death in patients on maintenance hemodialysis therapy. During hemodialysis sessions, the gradient between serum and dialysate levels results in rapid electrolyte shifts, which may contribute to arrhythmias and sudden death. Controversies exist about the optimal electrolyte concentration in the dialysate; specifically, it is unclear whether patient outcomes differ among those treated with a dialysate potassium concentration of 3 mEq/L compared to 2 mEq/L. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 55,183 patients from 20 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 1 to 5 (1996-2015). PREDICTOR: Dialysate potassium concentration at study entry. OUTCOMES: Cox regression was used to estimate the association between dialysate potassium concentration and both all-cause mortality and an arrhythmia composite outcome (arrhythmia-related hospitalization or sudden death), adjusting for potential confounders. RESULTS: During a median follow-up of 16.5 months, 24% of patients died and 7% had an arrhythmia composite outcome. No meaningful difference in clinical outcomes was observed for patients treated with a dialysate potassium concentration of 3 versus 2 mEq/L (adjusted HRs were 0.96 [95% CI, 0.91-1.01] for mortality and 0.98 [95% CI, 0.88-1.08] for arrhythmia composite). Results were similar across predialysis serum potassium levels. As in prior studies, higher serum potassium level was associated with adverse outcomes. However, dialysate potassium concentration had only minimal impact on serum potassium level measured predialysis (+0.09 [95% CI, 0.05-0.14] mEq/L serum potassium per 1 mEq/L greater dialysate potassium concentration). LIMITATIONS: Data were not available for delivered (vs prescribed) dialysate potassium concentration and postdialysis serum potassium level; possible unmeasured confounding. CONCLUSIONS: In combination, these results suggest that approaches other than altering dialysate potassium concentration (eg, education on dietary potassium sources and prescription of potassium-binding medications) may merit further attention to reduce risks associated with high serum potassium levels.