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.

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.

Kidney Health Initiative ESKD Data Standards Project.

The end-stage kidney disease (ESKD) Data Standards Project was launched by the Kidney Health Initiative (KHI) with the goal of standardizing dialysis-related measurements for research use. KHI is a public-private partnership between the American Society of Nephrology, US Food and Drug Administration, and organizations with an interest in kidney disease. KHI promotes safe and effective patient-centered therapies for people with kidney disease. In 2018, KHI established a workgroup with expertise in nephrology, nursing, quality management, ESKD data, organizational management, and clinical research. The workgroup identified 5 topic areas and 8 specific measures for the development of standards on the basis of the existing ESKD Measurement Specification Manual published by the Centers for Medicare & Medicaid Services. The topic areas were ultrafiltration rate, vascular access, dialysis small solute clearance (3 data standards), hospitalization (2 data standards), and mortality. The research standards were approved by the workgroup, reviewed by external reviewers, and opened to public comment. The data standards attempt to achieve balance between brevity and completeness in the face of knowledge gaps. The ESKD Data Standards are publicly available on the KHI website (https://khi.asn-online.org/projects/project.aspx?ID=78).

Conceptual Framework for Patient-Reported Outcome Measures in Clinical Trials of Skeletal Muscle Cramping Experienced in Dialysis: A Kidney Health Initiative Workgroup Report.

Skeletal muscle cramping is a common and bothersome symptom for patients on maintenance dialysis therapy, regardless of modality, and it has not been prioritized for innovative assessments or treatments. Research to prevent or treat skeletal muscle cramping in patients receiving dialysis is hindered by poorly understood pathophysiology, lack of an accepted definition, and the absence of a standardized measurement method. The Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a multidisciplinary workgroup to define a set of patient-reported outcome measures for use in clinical trials to test the effect of new dialysis devices, new KRTs, lifestyle/behavioral modifications, and medications on skeletal muscle cramping. Upon determining that foundational work was necessary, the workgroup undertook a multistep process to elicit concepts central to developing the basis for demonstrating content validity of candidate patient-reported outcome measures for skeletal muscle cramping in patients on dialysis. The workgroup sought to (1) create an accepted, patient-endorsed definition for skeletal muscle cramping that applies to all dialysis modalities, (2) construct a conceptual model for developing and evaluating a skeletal muscle cramping-specific patient-reported outcome measure, and (3) identify potential questions from existing patient-reported outcome measures that could be modified or adapted and subsequently tested in the dialysis population. We report the results of the workgroup's efforts, provide our recommendations, and issue a call to action to address the gaps in knowledge and research needs we identified. These action steps are urgently needed to quantify skeletal muscle cramping burden, assess the effect, and measure meaningful changes of new interventions to improve the experience of patients receiving dialysis and suffering from skeletal muscle cramping.

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.

"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.

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.

Ene-reductase transformation of massoia lactone to δ-decalactone in a continuous-flow reactor.

The demand for natural food flavorings increases every year. Biotransformation has become an attractive approach to obtain natural products. In this work, enantiomerically pure (R)-(+)-δ-decalactone was obtained by reduction of the C=C double bond of natural massoia lactone in a continuous-flow reactor. Of 13 different ene-reductases isolated, purified and tested, OYE3 was found to be the most efficient biocatalyst. The selected biocatalyst, either in the form of purified enzyme, cell lysate, whole cells or immobilized cells, was tested in the batch system as well as in the packed-bed flow bioreactor. The biotransformation performed in batch mode, using Ca2+-alginate immobilized cells of Escherichia coli BL21(DE3)/pET30a-OYE3, furnished the desired product with complete conversion in 30 min. The process was intensified using a continuous-flow reactor-membrane filtration system (flow 0.1 mL/min, substrate concentration 10 mM, pH 7, 24 °C) with cell lysate as biocatalyst combined with a cofactor regeneration system, which allowed obtaining > 99% bioconversion of massoia lactone.

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.

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.

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.

Combinations of mineral and bone disorder markers and risk of death and hospitalizations in the international Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Prior studies have developed a chronic kidney disease-mineral and bone disorder (CKD-MBD) composite score based on combinations of calcium (Ca), phosphorus (P) and parathyroid hormone (PTH) that have been shown to be associated with an increased risk of clinical outcomes in the USA. We examined this association in a contemporary, international cohort of hemodialysis patients. METHODS: We studied 19 313 patients surviving ≥12 months in the Dialysis Outcomes and Practice Patterns Study Phases 3-5 (2005-15) from Europe, Canada and the USA. The CKD-MBD composite score was defined as the number of markers above target levels (P, 3.5-5.5 mg/dL; Ca, 8.4-10.2 mg/dL; PTH, 150-600 pg/mL). Using Cox models, we estimated hazard ratios (HRs) for death and a composite event (death or hospitalization), contrasting MBD 2/3 (2-3 parameters above target) with MBD 0 (all in target), adjusted for a disease risk score (DRS). RESULTS: MBD 2/3 above target was observed in 10-14% of patients across regions and was associated with greater DRS-adjusted mortality {HR 1.41 [95% confidence interval (CI) 1.10-1.82]} and composite events [HR 1.23 (95% CI 1.10-1.38)] in the USA compared with MBD 0; the mortality association was stronger for patients ≥ 65 years of age [HR 1.82 (95% CI 1.28-2.58)] compared with patients <65 years of age [HR 1.11 (95% CI 0.80-1.55)]. HRs observed in Canada and Europe were generally consistent but weaker. Estimates for MBD 2/3 outside target (above or below) were slightly lower in all regions. CONCLUSIONS: Simultaneous consideration of Ca, P and PTH may help in identifying patients on dialysis with a higher risk of major clinical outcomes related to CKD-MBD.

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.

Increased Risk of Bone Fractures in Hemodialysis Patients Treated with Proton Pump Inhibitors in Real World: Results from the Dialysis Outcomes and Practice Patterns Study (DOPPS).

Long-term treatment with proton pump inhibitors (PPIs) is associated with an increased risk of fractures in the general population. PPIs are widely prescribed to dialysis patients but to date no study has specifically tested, by state-of-art statistical methods, the relationship between use of PPIs and fractures in this patient population. This study aimed to assess whether use of PPIs is associated with bone fractures (ie, hip fractures and fractures other than hip fractures) in a large international cohort of hemodialysis patients. We considered an observational prospective cohort of 27,097 hemodialysis patients from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Data analysis was performed by the Fine and Gray method, considering the competitive risk of mortality, as well as by a cause-specific hazards Cox model with death as a censoring event and matching patients according to the prescription time. Of 27,097 hemodialysis patients, 13,283 patients (49%) were on PPI treatment. Across the follow-up period (median, 19 months), 3.8 bone fractures × 100 person-years and 1.2 hip fractures × 100 person-years occurred. In multiple Cox models, considering the competitive risk of mortality, the incidence rate of bone (subdistribution hazard ratio [SHR] 1.22; 95% CI, 1.10 to 1.36; p < 0.001) and hip fractures (SHR 1.35; 95% CI, 1.13 to 1.62; p = 0.001) was significantly higher in PPI-treated than in PPI-untreated patients. These findings also held true in multiple, cause-specific, hazards Cox models matching patients according to the prescription time (bone fractures: HR 1.47; 95% CI, 1.23 to 1.76; p < 0.001; hip fractures: HR 1.85; 95% CI, 1.37 to 2.50; p < 0.001). The use of PPIs requires caution and a careful evaluation of risks/benefits ratio in hemodialysis patients. © 2019 American Society for Bone and Mineral Research.

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.

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.