Predicting hospitalizations for patients with chronic kidney disease.

OBJECTIVES: Patients with chronic kidney disease (CKD) are at higher risk of being admitted to the hospital than the general population. Hospitalizations in patients with CKD are associated with higher medical costs and increased morbidity and mortality. Identification of patients with CKD who are at greatest risk of hospitalization may hold promise to improve clinical outcomes and enable judicious allocation of health care resources. STUDY DESIGN: Retrospective, observational cohort study. METHODS: Medicare Part A and Part B claims from calendar years 2017 and 2018 from 50,000 unique patients with a diagnosis of stage 3 to 5 CKD were used for this study. Data were split into training (n = 40,000) and test (n = 10,000) sets. A variety of model types were built to predict all-cause hospitalization within 90 days. RESULTS: The final model was a gradient-boosting machine with 399 input terms. The model demonstrated good ability to discriminate (area under the curve [AUC] for the receiver operating characteristic curve = 0.73), which was stable when tested in the test set (AUC = 0.73). The positive predictive value in the test set was 0.306, 0.240, and 0.216 at the 10%, 20%, and 30% thresholds, respectively. The sensitivity in the test set was 0.288, 0.453, and 0.609 at the 10%, 20%, and 30% thresholds, respectively. CONCLUSIONS: We developed an algorithm that uses medical claims to identify Medicare patients with CKD stages 3 to 5 who are at highest risk of being hospitalized in the near term. This algorithm could be used as a decision support tool for clinical programs focusing on management of patient populations with CKD.

Use of incremental peritoneal dialysis: impact on clinical outcomes and quality of life measure.

BACKGROUND: Incremental peritoneal dialysis (PD) can be defined as a PD prescription that is less than the standard, full dose prescription and is typically used for patients initiating PD with residual kidney function. It has been suggested that use of incremental peritoneal dialysis may help preserve residual kidney function and may offer better quality of life due to the lower treatment burden, however published evidence is limited. In this study we assessed the associations between incremental peritoneal dialysis use and both clinical outcomes and quality of life measures in a large cohort of incident peritoneal dialysis patients in the US. METHODS: We considered adult patients initiating peritoneal dialysis between 31 July, 2015 and 31 May, 2019 within a single dialysis organization. Patients with body weight < 40 kg, amputation, or an estimated glomerular filtration rate > 20 mL/min during the first 4 weeks on peritoneal dialysis were excluded. Patients were assigned to exposure groups based on peritoneal dialysis prescription during dialysis weeks 5-8. Incremental peritoneal dialysis was defined by treatment frequency, number of exchanges/day, and exchange volume (for continuous ambulatory peritoneal dialysis patients) or by treatment frequency and presence/absence of last fill (for automated peritoneal dialysis patients). Analyses were performed separately for continuous ambulatory peritoneal dialysis and automated peritoneal dialysis. For each analysis, incremental peritoneal dialysis patients were propensity score matched to eligible full-dose peritoneal dialysis patients. Patients were followed for a maximum of 12 months until censoring for loss to follow-up or study end. Outcomes were compared using Poisson models (mortality, hospitalization, peritoneal dialysis discontinuation), linear mixed models (estimated glomerular filtration rate), and paired t tests (KDQOL domain scores). RESULTS: Among continuous ambulatory peritoneal dialysis patients, compared to full-dose peritoneal dialysis, incremental peritoneal dialysis use was associated with better KDQOL scores on 3 domains: physical composite score (42.5 vs 37.7, p = 0.03), burden of kidney disease (60.2 vs 45.6, p = 0.003), effects of kidney disease (79.4 vs 72.3, p = 0.05). Hospitalization and mortality rates were numerically lower (0.77 vs 1.12 admits/pt-year, p = 0.09 and 5.0 vs 10.2 deaths/100 pt-years, p = 0.22), while no associations were found with estimated glomerular filtration rate or peritoneal dialysis discontinuation rate. Use of incremental peritoneal dialysis was not associated with any discernable effects on outcomes in automated peritoneal dialysis patients. CONCLUSION: These results suggest that there may be benefits of using incremental PD in the context of continuous ambulatory peritoneal dialysis, particularly with respect to quality of life as a prescription strategy when initiating peritoneal dialysis. While no significant benefits of incremental peritoneal dialysis were detected among patients initiating automated peritoneal dialysis, no detrimental effects of using incremental schedules were observed for either peritoneal dialysis type.

Urgent-start peritoneal dialysis: Association with outcomes.

The majority of end-stage kidney disease (ESKD) patients start dialysis without adequate pre-dialysis planning. Of these patients, the vast majority initiate in-centre haemodialysis using a central venous catheter (ICHD-CVC). A minority utilise urgent-start peritoneal dialysis (USPD), whereby a peritoneal dialysis catheter is placed and used for dialysis without the usual 2-4-week waiting period. In this multicentre, retrospective study of adult patients initiating dialysis during 2018, we compared outcomes among patients utilising these two dialysis initiation routes. Patients who initiated dialysis via ICHD-CVC were matched 1:1 to patients who utilised USPD on the basis of aetiology of ESKD, race, diabetes status and insurance type. Hospitalisation and mortality were evaluated from dialysis initiation through the first of death, transplant, loss to follow-up or study end (30 June 2019). Outcomes were compared using models adjusted for age and sex. A total of 717 USPD patients were matched to ICHD-CVC patients. During follow-up, USPD patients were hospitalised at a rate of 1.21 admissions/patient-year (pt-yr) versus 1.51 admissions/pt-yr for ICHD-CVC. This corresponded to a 24% lower rate of hospitalisation among USPD patients (adjusted incidence rate ratio 0.76, 95% confidence interval [CI] 0.65-0.88). Mortality rates were 0.08 and 0.11 deaths/pt-yr among USPD patients and ICHD-CVC patients, respectively (adjusted hazard ratio 0.84, 95% CI 0.62, 1.15). These findings suggest that more widespread adoption of USPD may be beneficial among patients with limited pre-dialysis planning.

Dysnatremia and risk of bloodstream infection in dialysis patients.

Background: Emerging data suggest that sodium disarrays including hyponatremia are potential risk factors for infection ensuing from impairments in host immunity, which may be exacerbated by coexisting conditions (i.e. mucosal membrane and cellular edema leading to breakdown of microbial barrier function). While dysnatremia and infection-related mortality are common in dialysis patients, little is known about the association between serum sodium levels and the risk of bloodstream infection in this population. Methods: Among 823 dialysis patients from the national Biospecimen Registry Grant Program who underwent serum sodium testing over the period January 2008-December 2014, we examined the relationship between baseline serum sodium levels and subsequent rate of bloodstream infection. Bloodstream infection events were directly ascertained using laboratory blood culture data. Associations between serum sodium level and the incidence of bloodstream infection were estimated using expanded case mix-adjusted Poisson regression models. Results: In the overall cohort, ∼10% of all patients experienced one or more bloodstream infection events during the follow-up period. Patients with both lower sodium levels <134 mEq/l and higher sodium levels ≥140 mEq/l had higher incident rate ratios (IRRs) of bloodstream infection in expanded case mix analyses (reference 136-<138 mEq/l), with adjusted IRRs of 2.30 [95% confidence interval (CI) 1.19-4.44], 0.77 (95% CI 0.32-1.84), 1.39 (95% CI 0.78-2.47), 1.88 (95% CI 1.08-3.28) and 1.96 (95% CI 1.08-3.55) for sodium levels <134, 134-<136, 138-<140, 140-<142 and ≥142 Eq/l, respectively. Conclusions: Both lower and higher baseline serum sodium levels were associated with a higher rate of subsequent bloodstream infections in dialysis patients. Further studies are needed to determine whether correction of dysnatremia ameliorates infection risk in this population.

Utilization of Home Dialysis and Permanent Vascular Access at Dialysis Initiation Following a Structured CKD Education Program.

Rationale & Objective: Treatment options for kidney failure are complex, and the majority of patients transitioning to dialysis lack important information about treatment options and are not prepared to make informed decisions about their care. Correspondingly, the majority of patients who start dialysis default to in-center hemodialysis using a central venous catheter for vascular access as the initial modality; furthermore, hospital admissions, mortality, and infections are exceedingly common over the first few months. Study Design: Matched retrospective cohort study. Setting & Patients: 2,398 adult patients with chronic kidney disease (CKD) who attended a structured CKD education program and pair-matched control patients who did not receive education before starting dialysis between January 2018 and June 2019. Exposure: CKD education attendance documented from 2 months (60 days)-3 years before dialysis initiation. CKD education consisted of a 1-time, 90-minute, inperson or virtual class. Outcome: Primary outcomes were dialysis modality and vascular access type on the first day of dialysis (day 0) and at day 90 after dialysis initiation. Secondary outcomes included hospitalizations and deaths during the first year of receiving dialysis. Analytical Approach: Generalized linear models were used to compare outcomes between patients receiving CKD education and controls. Results: Compared with controls, CKD education patients were more frequently receiving home dialysis (38.5% vs 12.6%, P < 0.001) and used a permanent vascular access (57.9% vs 33.8%, P < 0.001) at dialysis initiation; differences were minimally attenuated and remained statistically significant at day 90. Hospitalization rates were lower among CKD education patients than among controls during the first year of receiving dialysis (1.00 vs 1.38 admissions per patient-year; P < 0.001). CKD education patients also had lower mortality over the first year of receiving dialysis (P < 0.001). Limitations: Bias and confounding cannot fully be accounted for in an observational study. Analyses only included patients with commercial and Medicare insurance who received CKD care before dialysis initiation and may not be generalizable to other patient populations. Conclusions: Our findings indicate that attending a CKD education class before starting dialysis resulted in positive clinical outcomes, including reduction in hospitalization and mortality rates. Broad implementation of structured CKD education may result in more patients choosing home dialysis as their first treatment option and reduce the risk of adverse outcomes in the crucial early period after dialysis initiation.

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.

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.

SARS-CoV-2 Antibody Seroprevalence Among Maintenance Dialysis Patients in the United States.

RATIONALE & OBJECTIVE: Reported coronavirus disease 2019 (COVID-19) cases underestimate the actual number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Patients receiving maintenance dialysis are at high risk for COVID-19 and higher case rates have been reported relative to the general population. To better understand infection patterns, we performed a seroprevalence study among maintenance dialysis patients at a large dialysis organization in the United States. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: We measured immunoglobulin G antibodies in an institutional review board-approved study of remnant serum samples collected for routine laboratory screenings in a national sample of 12,932 maintenance dialysis patients (May 27 to July 1, 2020). EXPOSURE: State, sex, age, and race. OUTCOMES: Seropositivity; ratio of seropositivity to known COVID-19 case rate. ANALYTIC APPROACH: Seropositivity was calculated overall and by state, sex, age, and race. The ratio of seropositivity to known COVID-19 cases was calculated overall and by state. RESULTS: 747 (5.8%) samples were seropositive. Seroprevalence varied by state and was lowest in Kentucky (1.0%) and highest in New York (23.6%). Seroprevalence was similar among men and women. Among samples from patients younger than 70 years, 6.0% to 6.5% were seropositive; whereas 5.2% and 3.9% of samples from patients aged 70 to 79 and 80 years or older, respectively, were seropositive. Samples from Black and Hispanic patients were 7.3% and 7.7% positive, respectively, compared with 2.8% of samples from White patients. After adjustment, risk differences among racial groups were lower but not eliminated. During the study period, the known COVID-19 case rate was 3.3%. The ratio of seropositivity to known COVID-19 cases was 1.7. LIMITATIONS: Imperfect assay sensitivity; results represent infections occurring before July 2020; deidentification prevented comparison of antibodies to previous COVID-19 status for individual patients; may not generalize to patients dialyzing with other providers or in other countries. CONCLUSIONS: Seroprevalence was 5.8% among dialysis patients as of July 1, 2020. This indicates that the actual number of infections was 1.7 times greater than reported cases. This ratio is lower than reported in the general population, suggesting that there were fewer unknown infections among maintenance dialysis patients.

Effect of ultrafiltration profiling on outcomes among maintenance hemodialysis patients: a pilot randomized crossover trial.

BACKGROUND: More rapid fluid removal during hemodialysis is associated with adverse cardiovascular outcomes and longer dialysis recovery times. The effect of ultrafiltration (UF) profiling, independent of concomitant sodium profiling, on markers of intradialytic hemodynamics and other outcomes has been inadequately studied. METHODS: Four-phase, blinded crossover trial. Participants (UF rates > 10 mL/h/kg) were assigned in random order to receive hemodialysis with UF profiling (constantly declining UF rate, intervention) vs. hemodialysis with conventional UF (control). Each 3-week 9-treatment period was followed by a 1-week 3-treatment washout period. Participants crossed into each study arm twice (2 phases/arm); 18 treatments per treatment type. The primary outcomes were intradialytic hypotension, pre- to post-dialysis troponin T change, and change from baseline in left ventricular global longitudinal strain. Other outcomes included intradialytic symptoms and blood volume measured-plasma refill (post-dialysis volume status measure), among others. Each participant served as their own control. RESULTS: On average, the 34 randomized patients (mean age 56 years, 24% female, mean dialysis vintage 6.3 years) had UF rates > 10 mL/h/kg in 56% of treatments during the screening period. All but 2 patients completed the 15-week study (prolonged hospitalization, kidney transplant). There was no significant difference in intradialytic hypotension, troponin T change, or left ventricular strain between hemodialysis with UF profiling and conventional UF. With UF profiling, participants had significantly lower odds of light-headedness and plasma refill compared to hemodialysis with conventional UF. CONCLUSIONS: Ultrafiltration (UF) profiling did not reduce the odds of treatment-related cardiac stress but did reduce the odds of light-headedness and post-dialysis hypervolemia. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03301740 (registered October 4, 2017).

Association of Chronic Condition Special Needs Plan With Hospitalization and Mortality Among Patients With End-Stage Kidney Disease.

Importance: While several studies have demonstrated the benefit of enrollment in chronic condition special needs plans (C-SNPs) for other chronic diseases (eg, diabetes), there is no evaluation of the association of C-SNPs with outcomes among patients with end-stage kidney disease (ESKD). Objective: To examine whether and to what degree C-SNP enrollment was associated with improved clinical outcomes and quality of life in patients with ESKD. Design, Setting, and Participants: This multicenter cohort study included 2718 patients who were newly enrolled in an ESKD C-SNP between January 1, 2013, and September 30, 2017, and receiving dialysis from DaVita Kidney Care. Patients were followed up until death, loss to follow-up, or end of study (ie, December 31, 2018). Enrollees in C-SNP were matched via multiple clinical and demographic characteristics with 2 different control populations, as follows: (1) those in the same facilities (n = 2545) or (2) those in similar counties (n = 1986). Patients enrolled in CareMore C-SNPs (n = 206) were excluded from the study. Data analysis was conducted June to December 2019. Exposures: Standard ESKD care with dialysis plus access to an integrated care team who worked with the patient and the dialysis team, comprehensive health assessments done by the integrated care team, and access to select benefits (such as vision and dental care) as a C-SNP enrollee. Main Outcomes and Measures: Hospitalizations, mortality, laboratory values indicative of metabolic control, and Kidney Disease Quality of Life 36-item (KDQOL-36) survey scores. Results: The 2545 C-SNP enrollees in the facility-matched analysis had a mean (SD) age of 57.2 (12.9) years, and included 968 (38.0%) women, 1328 (52.2%) Hispanic individuals, and 553 (21.7%) African American individuals. The 1986 C-SNP enrollees in the county-matched analysis had a mean (SD) age of 57.8 (12.2) years, with 705 (35.5%) women, 1085 (54.6%) Hispanic individuals, and 472 (23.8%) African American individuals. Compared with patients not enrolled in C-SNP, enrollees had lower hospitalization rates, with incidence rate ratios of 0.90 (95% CI, 0.84-0.97; P = .006) in the facility-matched analysis and 0.76 (95% CI, 0.70-0.83; P < .001) in the county-matched analysis. Compared with patients not enrolled in C-SNP, enrollees had decreased mortality risk in the same facilities (hazard ratio, 0.77; 95% CI, 0.68-0.88; P < .001) and in the same counties (hazard ratio, 0.77; 95% CI, 0.66-0.88; P < .001). No significant differences were observed between C-SNP enrollees and matched patients in metabolic laboratory values or KDQOL-36 survey scores. Conclusions and Relevance: This cohort study found a positive association of C-SNP enrollment with lower rates of hospitalization and mortality. The findings suggest that the additional services and benefits C-SNPs provide may improve outcomes compared with standard of care for patients with ESKD.

Impact of Rescheduling a Missed Hemodialysis Treatment on Clinical Outcomes.

RATIONALE & OBJECTIVE: Among patients treated with in-center hemodialysis (HD), missed treatments are associated with higher subsequent rates of hospitalization and other adverse outcomes compared with attending treatment. The objective of this study was to determine whether and to what degree attending a rescheduled treatment on the day following a missed treatment ameliorates these risks. STUDY DESIGN: Retrospective, observational. SETTING & PARTICIPANTS: Included patients were those who were, as of any of 12 index dates during 2014, adult Medicare beneficiaries treated with in-center HD (vintage ≥ 90 days) on a Monday/Wednesday/Friday schedule. EXPOSURE: Treatment attendance on the index date and the subsequent day. OUTCOMES: Hospital admissions, emergency department visits, mortality, blood pressure, and anemia measures, considered during the 7- and 30-day periods following exposure. ANALYTICAL APPROACH: In parallel analyses, patients who missed or rescheduled treatment were each matched (1:5) to patients who attended treatment on the index date on the basis of index day of week and propensity score. Within the matched cohorts, outcomes were compared across exposures using repeated-measures generalized linear models. RESULTS: Compared with attending treatment (N = 19,260), a missed treatment (N = 3,852) was associated with a 2.09-fold higher rate of hospitalization in the subsequent 7 days; a rescheduled treatment (N = 2,128) was associated with a 1.68-fold higher rate of hospitalization than attending (N = 10,640). Compared with attending treatment, hospitalization rates were 1.39- and 1.28-fold higher among patients who missed and rescheduled treatment, respectively, during the 30-day outcome period. Emergency department visits followed a similar pattern of associations as hospitalization. No statistically significant associations were observed with respect to mortality for either missed or rescheduled treatments compared with attending treatment. LIMITATIONS: Possible influence of unmeasured confounding; unknown generalizability to patients with non-Medicare insurance. CONCLUSIONS: Attending a rescheduled in-center HD treatment attenuates but does not fully mitigate the adverse effects of a missed treatment.

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.

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.

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.

Ultrafiltration-profiled hemodialysis to reduce dialysis-related cardiovascular stress: Study protocol for a randomized controlled trial.

Rapid fluid removal (ultrafiltration, UF) is associated with higher cardiovascular morbidity and mortality among individuals receiving maintenance hemodialysis (HD). Fluid removal rates that exceed vascular refill rates can result in hemodynamic instability, end-organ damage to the heart, kidneys, gut and brain, among other organs, and patient symptoms. There are no known evidence-based HD treatment strategies to reduce harm from higher UF rates. Ultrafiltration profiling, the practice of varying UF rates to maximize fluid removal during periods of greatest hydration and plasma oncotic pressure, has been proposed as an HD treatment intervention that may reduce UF rate-related complications. This study is a randomized 4-phase cross-over trial in which participants are successively alternated between study arms with intervening washout periods, and treatment order is randomized. After 4-week screening and 6-week baseline periods, participants are randomized to HD with conventional UF or HD with UF profiling for a period of 3 weeks followed by a 1-week washout period before crossing over. Participants cross into conventional UF and UF profiling phases twice (2 phases per arm). The primary outcomes of interest are intradialytic hypotension (nadir intradialytic systolic blood pressure <90 mmHg), pre-to post-HD change in troponin T (expressed as a percentage), change in left ventricular global longitudinal strain (an echocardiographic measure of left ventricular systolic function), and development of intradialytic left ventricular stunning (worsening of contractile function in ≥2 segments). This study will determine the impact of UF profiling on UF rate-related cardiovascular complications in prevalent, maintenance HD patients.

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.

The TiME Trial: A Fully Embedded, Cluster-Randomized, Pragmatic Trial of Hemodialysis Session Duration.

BACKGROUND: Data from clinical trials to inform practice in maintenance hemodialysis are limited. Incorporating randomized trials into dialysis clinical care delivery should help generate practice-guiding evidence, but the feasibility of this approach has not been established. METHODS: To develop approaches for embedding trials into routine delivery of maintenance hemodialysis, we performed a cluster-randomized, pragmatic trial demonstration project, the Time to Reduce Mortality in ESRD (TiME) trial, evaluating effects of session duration on mortality (primary outcome) and hospitalization rate. Dialysis facilities randomized to the intervention adopted a default session duration ≥4.25 hours (255 minutes) for incident patients; those randomized to usual care had no trial-driven approach to session duration. Implementation was highly centralized, with no on-site research personnel and complete reliance on clinically acquired data. We used multiple strategies to engage facility personnel and participating patients. RESULTS: The trial enrolled 7035 incident patients from 266 dialysis units. We discontinued the trial at a median follow-up of 1.1 years because of an inadequate between-group difference in session duration. For the primary analysis population (participants with estimated body water ≤42.5 L), mean session duration was 216 minutes for the intervention group and 207 minutes for the usual care group. We found no reduction in mortality or hospitalization rate for the intervention versus usual care. CONCLUSIONS: Although a highly pragmatic design allowed efficient enrollment, data acquisition, and monitoring, intervention uptake was insufficient to determine whether longer hemodialysis sessions improve outcomes. More effective strategies for engaging clinical personnel and patients are likely required to evaluate clinical trial interventions that are fully embedded in care delivery.

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.