Search

Aims: Lower haemoglobin levels are common among females without kidney diseases. However, little is known about the sex-specific management of anaemia in haemodialysis patients., Methods: This prospective cohort study investigated the role of sex differences in the association between categorical baseline or time-varying haemoglobin levels and all-cause mortality via cox regression using data from 6890 patients in the Japan Dialysis Outcomes and Practice Patterns Study (J-DOPPS, 2005-2015). Likelihood ratio tests were used to evaluate the effect modification of sex on the relationship between haemoglobin and mortality., Results: A total of 781 patients died during the median follow-up of 31 months. Mortality risk, adjusted for case mix, varied between five haemoglobin categories, with the highest category (≥12 g/dL) having a hazard ratio of 0.73 (0.41-1.29) for females and 2.02 (1.03-3.95) for males versus 10-10.9 g/dL. Despite this difference, the p-value comparing the overall among males versus females was.35. Similar associations were observed in models stratified by patient age (<75 years), time on dialysis (≤1 year), and models lagging the haemoglobin exposure., Conclusion: The results based on this sample of Japanese haemodialysis patients did not support the hypothesis that the association between haemoglobin and survival differed by sex. We also could not conclude that the association was identical, as the parameter estimates are consistent with male patients having a relatively greater mortality risk than female patients at higher haemoglobin levels. More detailed investigations into the effects of higher haemoglobin levels by sex might help better understand strategies for anaemia management., (© 2022 Asian Pacific Society of Nephrology.)

Background: Studies suggested the association between blood flow rate (BFR) and mortality might be beyond dialysis adequacy. This study aimed to explore if BFR is an independent predictor of clinical outcomes in Chinese hemodialysis (HD) patients., Methods: This study included data from patients in China Dialysis Outcomes and Practice Patterns Study (DOPPS) Phase 5. Patients with a record of BFR were included, and demographic data, comorbidities, hospitalization, and death records were collected. Associations between BFR and all-cause mortality and hospitalization were analyzed using Cox regression models., Results: One thousand four hundred twelve (98.9%) patients were included. Most patients were with BFR < 300 ml/min. After full adjustment, each 10-ml/min increase of BFR was associated with a 6.4% decrease in all-cause mortality risk (HR: 0.936, 95% CI: 0.880-0.996) but not first hospitalization (HR: 0.987, 95% CI: 0.949-1.027). The impact of BFR on mortality may be more prominent in patients who were male gender, nondiabetic, albumin < 4.0 g/dl, and hemoglobin ≥ 9.0 g/dl., Conclusion: Increased BFR is independently associated with a lower risk of all-cause mortality within the range of BFR 200-300 ml/min. And this effect is more pronounced in patients who were male gender, nondiabetic, albumin < 4.0 g/dl, and hemoglobin ≥ 9.0 g/dl., (© 2021 Wiley Periodicals LLC.)

Background: Icodextrin has been shown in randomized controlled trials to benefit fluid management in peritoneal dialysis (PD). We describe international icodextrin prescription practices and their relationship to clinical outcomes., Methods: We analyzed data from the prospective, international PDOPPS, from Australia/New Zealand, Canada, Japan, the United Kingdom, and the United States. Membrane function and 24-hour ultrafiltration according to icodextrin and glucose prescription was determined at baseline. Using an instrumental variable approach, Cox regression, stratified by country, was used to determine any association of icodextrin use to death and permanent transfer to hemodialysis (HDT), adjusted for demographics, comorbidities, serum albumin, urine volume, transplant waitlist status, PD modality, center size, and study phase., Results: Icodextrin was prescribed in 1986 (35%) of 5617 patients, >43% of patients in all countries, except in the United States, where it was only used in 17% and associated with a far greater use of hypertonic glucose. Patients on icodextrin had more coronary artery disease and diabetes, longer dialysis vintage, lower residual kidney function, faster peritoneal solute transfer rates, and lower ultrafiltration capacity. Prescriptions with or without icodextrin achieved equivalent ultrafiltration (median 750 ml/d [interquartile range 300-1345 ml/d] versus 765 ml/d [251-1345 ml/d]). Icodextrin use was not associated with mortality (HR=1.03; 95% CI, 0.72 to 1.48) or HDT (HR 1.2; 95% CI, 0.92 to 1.57)., Conclusions: There are large national and center differences in icodextrin prescription, with the United States using significantly less. Icodextrin was associated with hypertonic glucose avoidance but equivalent ultrafiltration, which may affect any potential survival advantage or HDT., Competing Interests: S.J. Davies received consulting fees from Baxter Healthcare and Ellen Medical, and honoraria from Fresenius Medical Care. T. Kanjanabuch received consultancy fees from VISTERA as a country investigator and current recipient of the National Research Council of Thailand and Innovation Fund Chulalongkorn University. received speaking honoraria from AstraZeneca and Baxter Healthcare. K.P. McCullough, R.L. Pisoni, B.M. Robinson, and J. Zhao are employees of Arbor Research Collaborative for Health, which funds the DOPPS. R. Mehrotra received consulting fee from Baxter Healthcare. J. Perl received grants from AHRQ; consulting fee from Baxter Healthcare, Davita, Fresenius Medical Care, and Otsuka; honoraria from Baxter Healthcare, Davita Healthcare Partners, DCI, Fresenius Medical Care, and US Renal Care; support for attending meetings and/or travel from Liberdi Dialysis; and stock or stock options from Liberdi dialysis. B.M. Robinson received consultancy fees or travel reimbursement since 2018 from AstraZeneca, GlaxoSmithKline, and Kyowa Kirin Co., all paid directly to his institution of employment. A.Y.-M. Wang participated on a Data Safety Monitoring Board or Advisory Board (DSMB ASPIRED TRIAL) and is International Society of Nephrology (ISN) Councilor and North and East Asia Regional Board Deputy Chair, ISN Education working group Deputy Chair Council Member of International Society of Peritoneal Dialysis, and President of International Society of Renal Nutrition and Metabolism. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Background: Hemodialysis (HD) patients have a higher mortality rate compared with general population. Our previous study revealed that platelet counts might be a potential risk factor. The role of platelets in HD patients has rarely been studied. The aim of this study is to examine if there is an association of thrombocytopenia (TP) with elevated risk of all-cause mortality and cardiovascular (CV) death in Chinese HD patients., Methods: Data from a prospective cohort study, China Dialysis Outcomes and Practice Patterns Study (DOPPS) 5, were analyzed. Demographic data, comorbidities, platelet counts and other lab data, and death records which extracted from the medical record were analyzed. TP was defined as the platelet count below the lower normal limit (< 100*10 9 /L). Associations between platelet counts and all-cause and CV mortality were evaluated using Cox regression models. Stepwise multivariate logistic regression was used to identify the independent associated factors, and subgroup analyses were also carried out., Results: Of 1369 patients, 11.2% (154) had TP at enrollment. The all-cause mortality rates were 26.0% vs. 13.3% (p < 0.001) in patients with and without TP. TP was associated with higher all-cause mortality after adjusted for covariates (HR:1.73,95%CI:1.11,2.71), but was not associated with CV death after fully adjusted (HR:1.71,95%CI:0.88,3.33). Multivariate logistic regression showed that urine output < 200 ml/day, cerebrovascular disease, hepatitis (B or C), and white blood cells were independent impact factors (P < 0.05). Subgroup analysis found that the effect of TP on all-cause mortality was more prominent in patients with diabetes or hypertension, who on dialysis thrice a week, with lower ALB (< 4 g/dl) or higher hemoglobin, and patients without congestive heart failure, cerebrovascular disease, or hepatitis (P < 0.05)., Conclusion: In Chinese HD patients, TP is associated with higher risk of all-cause mortality, but not cardiovascular mortality. Platelet counts may be a useful prognostic marker for clinical outcomes among HD patients, though additional study is needed., (© 2021. The Author(s).)

Background: The Japanese Society for Dialysis Therapy (JSDT) published in 2013 inaugural hemodialysis (HD) guidelines. Specific targets include 1.4 for single-pool Kt/V (spKt/V) with a minimum dose of 1.2, minimum dialysis session length of 4 hours, minimum blood flow rate (BFR) of 200 mL/min, fluid removal rate no more than 15 mL/kg/hr, and hemodiafiltration (HDF) therapy for certain identified symptoms. We evaluated the effect of these guidelines on actual practice in the years spanning 2005 - 2018., Methods: Analyses were carried out to describe trends in the above HD prescription practices from December 2005 to April 2013 (before guideline publication) to August 2018 based on prevalent patient cross-sections from approximately 60 randomly selected HD facilities participating in the Japan Dialysis Outcomes and Practice Patterns Study., Results: From April 2006 to August 2017 continual rises occurred in mean spKt/V (from 1.35 to 1.49), and percent of patients having spKt/V>1.2 (71% to 85%). Mean BFR increased with time from 198.3 mL/min (April 2006) to 218.4 mL/min (August 2017) , along with percent of patients with BFR >200 ml/min (65% to 85%). HDF use increased slightly from 6% (April 2006 and August 2009) to 8% by April 2013, but increased greatly thereafter to 23% by August 2017. In contrast, mean HD treatment time showed little change from 2006-2017, whereas mean UFR declined from 11.3 in 2006 to 8.4 mL/Kg/hour in 2017., Conclusions: From 2006 - 2018 Japanese HD patients experienced marked improvement in reaching the spKt/V target specified by the 2013 JSDT guidelines. This may have been due to moderate increase in mean BFR even though mean HD session length did not change much. In addition, HDF use increased dramatically in this time period. Other HD delivery changes during this time, such as increased use of super high flux dialyzers, also merit study. While we cannot definitively conclude a causal relationship between the publication of the guidelines and the subsequent practice changes in Japan, those changes moved practice closer to the recommendations of the guidelines., (© 2021. The Author(s).)

Rationale & Objective: Optimizing vascular access use is crucial for long-term hemodialysis patient care. Because vascular access use varies internationally, we examined international differences in arteriovenous fistula (AVF) patency and time to becoming catheter-free for patients receiving a new AVF., Study Design: Prospective cohort study., Setting & Participants: 2,191 AVFs newly created in 2,040 hemodialysis patients in 2009 to 2015 at 466 randomly selected facilities in the Dialysis Outcomes and Practice Patterns Study (DOPPS) from the United States, Japan, and EUR/ANZ (Belgium, France, Germany, Italy, Spain, Sweden, United Kingdom, Australia, and New Zealand)., Predictors: Demographics, comorbid conditions, dialysis vintage, body mass index, AVF location, and country/region., Outcomes: Primary/cumulative AVF patency (from creation), primary/cumulative functional patency (from first use), catheter dependence duration, and mortality., Analytical Approach: Outcomes estimated using Cox regression., Results: Across regions, mean patient age ranged from 61 to 66 years, with male preponderance ranging from 55% to 66%, median dialysis vintage of 0.3 to 3.2 years, with 84%, 54%, and 32% of AVFs created in the forearm in Japan, EUR/ANZ, and United States, respectively. Japan displayed superior primary and cumulative patencies due to higher successful AVF use, whereas cumulative functional patency was similar across regions. AVF patency associations with age and other patient characteristics were weak or varied considerably between regions. Catheter-dependence following AVF creation was much longer in EUR/ANZ and US patients, with nearly 70% remaining catheter dependent 8 months after AVF creation when AVFs were not successfully used. Not using an arteriovenous access within 6 months of AVF creation was related to 53% higher mortality in the subsequent 6 months., Limitations: Residual confounding., Conclusions: Our findings highlight the need to reevaluate practices for optimizing long-term access planning and achievable AVF outcomes, especially AVF maturation. New AVFs that are not successfully used are associated with long-term catheter exposure and elevated mortality risk. These findings highlight the importance of selecting the best access type for each patient and developing effective clinical pathways for when AVFs fail to mature successfully., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The number of patients on hemodialysis (HD) is rapidly increasing in China. As an Asian country with a large number of HD patients, understanding the status of Chinese HD patients has a special significance. We reported here the baseline data for China Dialysis Outcomes and Practice Pattern Study Phase 5 (DOPPS5). The DOPPS is an international prospective, observational cohort study. Patients were restricted to the initial sample of patients who participated in China DOPPS5. We summarized the baseline demographic and clinical data of patients. Results were weighted by facility sampling fraction. 1186 patients were initial patients in China DOPPS5. The mean age was 58.7 ± 3.5 years, with 54.6% males. The median dialysis vintage was 3.4 (1.5, 6.3) years. The main assigned primary end-stage kidney disease (ESKD) causes was chronic glomerulonephritis (45.9%), followed by diabetes (19.9%). 17.6% patients had hepatitis B infection, and 10.0% patients had hepatitis C infection. 25.9% patients had a single-pooled Kt/V < 1.2. 86.6% patients had albumin > 3.5 g/dl. 18.8% patients had hemoglobin < 9 g/dl. 66.5% patients had serum calcium in target range (8.4-10.2 mg/dl), 41.5% patients had serum phosphate in target range (3.5-5.5 mg/dl) and 51.2% patients maintained PTH in 150-600 pg/dl. 88.2% patients used fistula as their vascular access. Meanwhile, there were differences in the demographic, clinical, laboratory, and treatment characteristics among the three cities participated in China DOPPS. We observed a relatively higher albumin level and a higher rate of fistula usage in our patients. But it remains a major challenge to us on the management of CKD-MBD and anemia. This study did not include patients in small cities and remote areas, where the situation of HD patients might be worse than reported.

Background: Fibroblast growth factor 23 (FGF23) plays an important role in chronic kidney disease (CKD)-related mineral and bone disorders. High FGF23 levels are associated with increased risk of anaemia in non-haemodialysis CKD patients. FGF23 also negatively regulates erythropoiesis in mice. We hypothesized that higher FGF23 levels are associated with increased erythropoietin hyporesponsiveness among haemodialysis patients., Methods: The study included 1044 patients from the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS) phase 5 (2012-2015). The outcome was erythropoiesis-stimulating agent hyporesponsiveness (ESA-hypo), defined as mean Hgb <10 g/dL and standardized mean ESA dose >6000 u/week over 4 months following FGF23 measurement. The association between ESA-hypo and FGF23 was estimated using multivariable-adjusted logistic generalized estimating equation regression models., Results: Patients with higher levels of FGF23 were younger and had higher levels of serum albumin, creatinine, albumin-corrected calcium, phosphorus, PTH, 25(OH)-vitamin D, and had higher percentages of intravenous (IV) iron, IV vitamin D and cinacalcet use. ESA-hypo was present in 144 patients (13.8%). Compared with the third quintile of FGF23 levels, the odds ratio (95% CI) of ESA-hypo was 2.14 (0.99, 4.62) and 1.74 (0.74, 4.11) for the first and fifth quintiles, respectively., Conclusion: The lowest and highest levels of FGF23 were associated with higher odds of ESA-hypo in patients on maintenance haemodialysis, although the associations were not statistically significant. The relationship between FGF23 and anaemia, and particularly the increased risks of ESA-hypo at low FGF23 levels which might be the result of energy saving, must be confirmed in larger clinical studies., (© 2020 The Authors. Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology.)

Background: Optimal parathyroid hormone (PTH) control during non-dialysis chronic kidney disease (ND-CKD) might decrease the subsequent risk of parathyroid hyperplasia and uncontrolled secondary hyperparathyroidism (SHPT) on dialysis. However, the evidence for recommending PTH targets and therapeutic strategies is weak for ND-CKD. We evaluated the patient characteristics, treatment patterns and PTH control over the first year of haemodialysis (HD) by PTH prior to HD initiation., Methods: We studied 5683 incident HD patients from 21 countries in Dialysis Outcomes and Practice Patterns Study Phases 4-6 (2009-18). We stratified by PTH measured immediately prior to HD initiation and reported the monthly prescription prevalence of active vitamin D and calcimimetics over the first year of HD and risk of PTH >600 pg/mL after 9-12 months on HD., Results: The 16% of patients with PTH >600 pg/mL prior to HD initiation were more likely to be prescribed active vitamin D and calcimimetics during the first year of HD. The prevalence of PTH >600 pg/mL 9-12 months after start of HD was greater for patients who initiated HD with PTH >600 (29%) versus 150-300 (7%) pg/mL (adjusted risk difference: 19%; 95% confidence interval : 15%, 23%). The patients with sustained PTH >600 pg/mL after 9-12 months on HD were younger, more likely to be black, and had higher serum phosphorus and estimated glomerular filtration rates at HD initiation., Conclusions: Increased PTH before HD start predicted a higher PTH level 9-12 months later, despite greater use of active vitamin D and calcimimetics. More targeted PTH control during ND-CKD may influence outcomes during HD, raising the need for PTH target guidelines in these patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Introduction: Dipeptidyl peptidase-4 (DPP-4) has been hypothesized to improve responsiveness to erythropoiesis-stimulating agent (ESA). We aimed to describe the trend in DPP-4 inhibitor prescription patterns and assess the association between DPP-4 inhibitor prescription and ESA hyporesponsiveness (eHypo) in Japanese hemodialysis (HD) patients with diabetes mellitus (DM)., Methods: We analyzed data from the Japan Dialysis Outcomes and Practice Patterns Study phase 4-6 (2009-2017) on patients with DM who underwent HD thrice per week for at least 4 months. The primary exposure of interest was having a DPP-4 inhibitor prescription. The primary analysis outcomes were a binary indicator of eHypo (mean hemoglobin <10 and mean ESA dose >6,000 units/week over 4 months) and the natural log-transformed ESA resistance index (ERI). We used conditional logistic regression to compare within-patient changes in eHypo before and after initial DPP-4 inhibitor prescription. We used linear generalized estimating equation models to compare continuous ERI outcomes while accounting for within-patient repeated measurements with an exchangeable correlation structure., Results: There was a monotonic increase in DPP-4 inhibitor prescription according to study year up to 20% in 2017. Moreover, 12.8% of patients with a DPP-4 inhibitor prescription were ESA hyporesponsive before the initial DPP-4 inhibitor prescription. After DPP-4 inhibitor prescription, the odds of eHypo and mean log-ERI remained unchanged in the whole cohort of our study. The interaction analysis of DPP-4 inhibitor and sideropenia showed that DPP-4 inhibitors attenuated eHypo in the patients without iron deficiency., Conclusion: Our findings indicate a recent increase in DPP-4 inhibitor prescription among Japanese HD patients with DM. DPP-4 inhibitors could improve ERI in patients undergoing HD without iron deficiency., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Background: Serial assessment of phosphorus is currently recommended by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, but its additional value versus a single measurement is uncertain., Methods: We studied data from 17 414 HD patients in the Dialysis Outcomes and Practice Patterns Study, a prospective cohort study, and calculated the area under the curve (AUC) by multiplying the time spent with serum phosphorus >4.5 mg/dL over a 6-month run-in period by the extent to which this threshold was exceeded. We estimated the association between the monthly average AUC and cardiovascular (CV) mortality using Cox regression. We formally assessed whether AUC was a better predictor of CV mortality than other measures of phosphorus control according to the Akaike information criterion., Results: Compared with the reference group of AUC = 0, the adjusted hazard ratio (HR) of CV mortality was 1.12 [95% confidence interval (CI) 0.90-1.40] for AUC > 0-0.5, 1.26 (95% CI 0.99-1.62) for AUC > 0.5-1, 1.44 (95% CI 1.11-1.86) for AUC > 1-2 and 2.03 (95% CI 1.53-2.69) for AUC > 2. The AUC was predictive of CV mortality within strata of the most recent phosphorus level and had a better model fit than other serial measures of phosphorus control (mean phosphorus, months out of target)., Conclusions: We conclude that worse phosphorus control over a 6-month period was strongly associated with CV mortality. The more phosphorus values do not exceed 4.5 mg/dL the better is survival. Phosphorus AUC is a better predictor of CV death than the single most recent phosphorus level, supporting with real-world data KDIGO's recommendation of serial assessment of phosphorus to guide clinical decisions., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: The prospective Dialysis Outcomes and Practice Patterns Study (DOPPS) has collected data since 2012 in all six Gulf Cooperation Council (GCC) countries (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and United Arab Emirates). We report the relationship of PTH with mortality in this largest GCC cohort of patients on hemodialysis studied to date., Methods: Data were from randomly selected national samples of hemodialysis facilities in GCC-DOPPS phases 5 and 6 (2012-2018). PTH descriptive findings and case mix-adjusted PTH/mortality Cox regression analyses were based on 1825 and 1422 randomly selected patients on hemodialysis, respectively., Results: Mean patient age was 55 years (median dialysis vintage, 2.1 years). Median PTH ranged from 259 pg/ml (UAE) to 437 pg/ml (Kuwait), with 22% having PTH <150 pg/ml, 24% with PTH of 150-300 pg/ml, 34% with PTH 301-700 pg/ml, and 20% with PTH >700 pg/ml. Patients with PTH >700 pg/ml were younger; on dialysis longer; less likely to be diabetic; have urine >200 ml/d; be prescribed 3.5 mEq/L dialysate calcium; had higher mean serum creatinine and phosphate levels; lower white blood cell counts; and more likely to be prescribed cinacalcet, phosphate binders, or IV vitamin D. A U-shaped PTH/mortality relationship was observed with more than two- and 1.5-fold higher adjusted HR of death at PTH >700 pg/ml and <300 pg/ml, respectively, compared with PTH of 301-450 pg/ml., Conclusions: Secondary hyperparathyroidism is highly prevalent among GCC patients on hemodialysis, with a strong U-shaped PTH/mortality relationship seen at PTH <300 and >450 pg/ml. Future studies are encouraged for further understanding this PTH/mortality pattern in relationship to unique aspects of the GCC hemodialysis population., Competing Interests: B. Bieber, R. Pisoni, and B. Robinson report receiving grants from Amgen, during the conduct of the study. E. Fouly reports receiving salary from his company, Amgen, during the conduct of the study, which was supported by Amgen. In addition, E. Fouly’s company, Amgen, has licensed patents for cinacalcet and etelcalcetide, which are drugs used to treat sHPT and are thus related to the topic of this paper. This project was carried out as part of the DOPPS Program which receives global support from a large consortium of funders listed at https://www.dopps.org/AboutUs/Support.aspx. All such grants were made to Arbor Research Collaborative for Health and not to coauthors directly. All remaining authors have nothing to disclose., (Copyright © 2020 by the American Society of Nephrology.)

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., (© 2019 American Society for Bone and Mineral Research.)

Background: Haemodialysis patients experience a wide variety of intermediate complications, such as anaemia, hypertension and mineral bone disease (MBD). We aimed to assess the risk of death and hospital admissions as a function of the simultaneous attainment of different guideline targets (for hypertension, anaemia and MBD) in a large European cohort of dialysis patients., Methods: EURODOPPS is part of the Dialysis Outcomes and Practice Patterns Study (DOPPS) international, prospective cohort study of adult, in-centre haemodialysis patients for whom clinical data are extracted from medical records. In the present analysis, 6317 patients from seven European countries were included between 2009 and 2011. The percentages of patients treated according to the international guidelines on anaemia, hypertension and MBD were determined. The overall degree of guideline attainment was considered to be high if four or all five of the evaluated targets were attained, moderate if two or three targets were attained, and low if fewer than two targets were attained. Fully adjusted multivariate Cox models were used to investigate the relationship of target attainment with mortality and first hospital admission., Results: At baseline, the degree of target attainment was low in 1751 patients (28%), moderate in 3803 (60%) and high in 763 (12%). In the fully adjusted model using time-dependent covariates, low attainment was associated with higher all-cause mortality [hazard ratio (95% confidence interval) = 1.19 (1.05-1.34)] and high attainment was associated with lower all-cause mortality [0.82 (0.68-0.99)]. In a similar model that additionally accounted for death as a competing risk, low and high attainments were not associated with hospital admission., Conclusion: In a large international cohort of dialysis patients, we have shown that more stringent application of guidelines is associated with lower mortality., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: On the first haemodialysis (HD) day after the 2-day break in three times a week (3×W) in-centre HD, mortality and hospitalization are higher. If longer HD sessions prescribed 3×W is associated with a reduction in these events is unknown., Methods: HD session length in 19 557 prevalent European in-centre 3×W HD patients participating in the Dialysis Outcomes and Practice Patterns Study (1998-2011) were categorized into <200, 200-225, 226-250 or >250 min. Standardized event rates on the first (HD1) versus the second (HD2) HD day after the 2-day break, with supporting Cox proportional hazards models adjusted for patient and dialysis characteristics, were generated for all-cause mortality, all-cause hospitalization, out-of-hospital death and fluid overload hospitalization., Results: By comparing HD1 with HD2, increased rates of all endpoints were observed (all P < 0.002). As HD session lengthened across the four groups, all-cause mortality per 100 patient-years on the HD1 (23.0, 20.4, 16.4 and 14.6) and HD2 (26.1, 13.3, 13.4 and 12.1) reduced. Similar improvements were observed for out-of-hospital death but were less marked for hospitalization endpoints. However, even patients dialysing >250 min were at significantly greater risk on HD1 when compared with their HD2 for out-of-hospital death [hazard ratio (HR) = 2.1, 95% CI 1.0-4.3], all-cause hospitalization (HR = 1.3, 95% CI 1.2-1.4) and fluid overload hospitalization (HR = 3.2, 95% CI 1.8-6.0)., Conclusions: Despite the association between reduced mortality across all dialysis days in patients performing longer sessions, elevated risk on the first dialysis day relative to the second persists even in patients dialysing 4.5 h 3×W., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Background and Objectives: Fluid overload and intradialytic hypotension are associated with cardiovascular events and mortality in patients on hemodialysis. We investigated associations between hemodialysis facility practices related to fluid volume and intradialytic hypotension and patient outcomes., Design, Setting, Participants, & Measurements: Data were analyzed from 10,250 patients in 273 facilities across 12 countries, from phase 4 of the Dialysis Outcomes and Practice Patterns Study (DOPPS; 2009-2012). Cox regression models (shared frailty) were used to estimate associations between facility practices reported by medical directors in response to the DOPPS Medical Directors Survey and all-cause and cardiovascular mortality and hospitalization, and cardiovascular events, adjusting for country, age, sex, dialysis vintage, predialysis systolic BP, cardiovascular comorbidities, diabetes, body mass index, smoking, residual kidney function, dialysis adequacy, and vascular access type., Results: Of ten facility practices tested (chosen a priori ), having a protocol that specifies how often to assess dry weight in most patients was associated with lower all-cause (hazard ratio [HR], 0.78; 99% confidence interval [99% CI], 0.64 to 0.94) and cardiovascular mortality (HR, 0.72; 99% CI, 0.55 to 0.95). Routine orthostatic BP measurement to assess dry weight was associated with lower all-cause hospitalization (HR, 0.86; 99% CI, 0.77 to 0.97) and cardiovascular events (HR, 0.85; 99% CI, 0.73 to 0.98). Routine use of lower dialysate temperature to limit or prevent intradialytic hypotension was associated with lower cardiovascular mortality (HR, 0.76; 99% CI, 0.58 to 0.98). Routine use of an online volume indicator to assess dry weight was associated with higher all-cause hospitalization (HR, 1.19; 99% CI, 1.02 to 1.38). Routine use of sodium modeling/profiling to limit or prevent intradialytic hypotension was associated with higher all-cause mortality (HR, 1.36; 99% CI, 1.14 to 1.63), cardiovascular mortality (HR, 1.34; 99% CI, 1.04 to 1.73), and cardiovascular events (HR, 1.21; 99% CI, 1.03 to 1.43)., Conclusions: Hemodialysis facility practices relating to the management of fluid volume and intradialytic hypotension are associated with patient outcomes., (Copyright © 2019 by the American Society of Nephrology.)

Background: The Kidney Disease: Improving Global Outcomes guidelines have cautioned against administering intravenous (IV) iron to hemodialysis patients with high serum ferritin levels due to safety concerns, but prior research has shown that the association between high ferritin and mortality could be attributed to confounding by malnutrition and inflammation. Our goal was to better understand the ferritin-mortality association and relative influence of IV iron and inflammation in the USA, where ferritin levels have recently increased dramatically, and in Europe and Japan, where ferritin levels are lower and anemia management practices differ., Methods: Data from 18 261 patients in Phases 4 and 5 (2009-15) of the international Dialysis Outcomes and Practice Patterns Study, a prospective cohort study, were analyzed. Using Cox regression, we modeled the association between baseline ferritin and 1-year mortality with restricted cubic splines and assessed the impact of potential confounders., Results: Median ferritin levels were 718 ng/mL in the USA, 405 in Europe and 83 in Japan. High ferritin levels were associated with elevated mortality (relative to region-specific medians) in all three regions. The strength of this association was attenuated more by adjustment for malnutrition and inflammation than by IV iron and erythropoiesis-stimulating agent dose in each region., Conclusion: The utility of high ferritin as a biomarker for clinical risk due to excess iron stores may be limited, although caution regarding IV iron dosing to higher upper ferritin targets remains warranted. Research to resolve biomarker criteria for iron dosing, and whether optimal anemia management strategies differ internationally, is still needed.

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., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: High-circulating level of parathyroid hormone (PTH) is associated with elevated mortality in dialysis patients. The Japanese Society for Dialysis Therapy guideline suggests a lower PTH target than other international guidelines; thus, PTH control may differ in Japan compared with other regions, and be associated with mortality., Methods: We analyzed data from hemodialysis patients with ≥3 measurements of PTH during the first 9 months after enrollment in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4-5 (2009-2015). PTH control was assessed by the mean, slope, and mean squared error (MSE) of all PTH measurements over the 9-month run-in period. Distribution of each PTH control was assessed by regions (Europe/Australia/New Zealand [Eur/ANZ], Japan and North America) and dialysis vintage. Mortality rates were compared across PTH control categories using Cox regression models., Results: Mean PTH was lower in Japan than in other regions across dialysis vintage categories. In patients with dialysis vintage < 90 days, PTH level was more likely to decline > 5% per month in Japan (48% of patients) versus Eur/ANZ (35%) and North America (35%). In patients with dialysis vintage > 1 year, Japanese patients maintained steady PTH, while patients in Eur/ANZ and North America were more likely to experience a PTH increase. Mean PTH was associated with mortality in the overall samples (highest mortality rate for PTH > 600 pg/mL, hazard ratio, 1.35; 95% confidence interval, 1.20 to 1.52 vs PTH 200-399 pg/mL), and the association was obvious in the prevalent patients (hazard ratio, 1.44; 95% confidence interval, 1.26 to 1.65). PTH slope and MSE did not show significant association with mortality in the overall sample as well as in subjects stratified both by region and dialysis vintage., Conclusion: PTH control in hemodialysis patients, as measured by keeping a stable PTH level over 9 months, was observed in Japan contrasted with other regions. High PTH mean, but not increased PTH slope and MSE, was associated with mortality especially in prevalent 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., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

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.

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., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Clinicians providing dialysis care have numerous erythropoiesis-stimulating agents (ESAs) available for treating anemia. We sought to provide a contemporary description of ESA types used in hemodialysis (HD) settings in nine European countries., Methods: Our study uses Dialysis Outcomes and Practice Patterns Study phase 5 (2012-2015) data from nine European countries (Belgium, France, -Germany, Italy, Russia, Spain, Sweden, Turkey, and the United Kingdom). A total of 164 facilities and 3,281 patients contributed cross-sectional data. ESA types captured included short-acting epoetins (e.g., epoetin alfa, beta, etc., including biosimilars), darbepoetin alfa, and continuous erythropoietin receptor agonist (CERA; methoxy polyethylene glycol-epoetin beta)., Results: We observed broad variability across countries in prescription of ESA types: prescription of epoetin alfa or epoetin beta ranged from 22% (France) to 78% (Russia), darbepoetin alfa prescription ranged from 13% (Russia) to 53% (UK), and CERA prescription ranged from <3% (Sweden) to 26% (France). Prescription of different ESA types varied substantially within some European countries from 2012-2015 but not across all countries in aggregate. Number of ESA types prescribed by a facility varied from 1, 2, 3, or 4 different ESA types in 32, 40, 21, and 8% of facilities, respectively. No differences were seen in the unadjusted distributions of achieved hemoglobin values by ESA type., Conclusion: A variety of short- and long-acting ESAs are commonly used in European HD facilities to maintain hemoglobin at remarkably similar levels with each ESA type. The availability of numerous ESA options for managing anemia has allowed European providers to optimize anemia management according to the particular circumstances of each patient., (© 2018 S. Karger AG, Basel.)

Background: Abnormal chronic kidney disease-mineral and bone disorder (CKD-MBD) markers have been associated with adverse outcomes in hemodialysis (HD) patients. Dialysate calcium concentration (D-Ca) likely influences serum calcium and phosphorus levels. Optimal D-Ca level remains unclear. We hypothesized that higher D-Ca is associated with cardiovascular events and mortality among Japanese HD patients., Methods: Enrollment data of chronic HD patients in the prospective observational study JDOPPS, phases 1-5 (1999-2015), provided exposures and covariates. All-cause mortality, non-arrhythmic cardiovascular events (NonAR-CVE), or their composites were analyzed by D-Ca, and divided into 2.5, 2.75, and 3.0 mEq/L. To minimize confounding by indication, analyses were restricted to facilities in which at least 90% of patients received the same D-Ca prescription. Association of D-Ca level with outcomes was evaluated in Cox models stratified by phase and accounting for facility clustering. Covariates describing patient demographics, comorbidities, laboratory values, CKD-MBD therapy, and facility attributes provided adjustment., Results: Of 9,201 patients included, 25.0% had D-Ca of 2.5 mEq/L; 6.8% D-Ca 2.75; and 68.2% D-Ca 3.0. Median follow-up time was 2.03 years. D-Ca was not associated with all-cause mortality, with hazards ratios for 2.5 vs. 3.0 mEq/L of 0.90 and 95% CI (0.73-1.11), nor with other outcomes. One effect modification occurred, protective for lower D-Ca on NonAR-CVE in the absence of cardiovascular comorbidities (p = 0.032), although corresponding D-Ca effects were not significant after multiple comparisons adjustment (p = 0.261 [D-Ca 2.5] and 0.125 [D-Ca 2.75])., Conclusion: Lowering D-Ca level below 3.0 mEq/L seems not to have a meaningful effect on patient outcomes., (© 2018 S. Karger AG, Basel.)

Background: Anemia management protocols in hemodialysis (HD) units differ conspicuously regarding optimal intravenous (IV) iron dosing; consequently, patients receive markedly different cumulative exposures to IV iron and erythropoiesis-stimulating agents (ESAs). Complementary to IV iron safety studies, our goal was to gain insight into optimal IV iron dosing by estimating the effects of IV iron doses on Hgb, TSAT, ferritin, and ESA dose in common clinical practice., Methods: 9,471 HD patients (11 countries, 2009-2011) in the DOPPS, a prospective cohort study, were analyzed. Associations of IV iron dose (3-month average, categorized as 0, <300, ≥300 mg/month) with 3-month change in Hgb, TSAT, ferritin, and ESA dose were evaluated using adjusted GEE models., Results: Relative change: Monotonically positive associations between IV iron dose and Hgb, TSAT, and ferritin change, and inverse associations with ESA dose change, were observed across multiple strata of prior Hgb, TSAT, and ferritin levels. Absolute change: TSAT, ferritin, and ESA dose changes were nearest zero with IV iron <300 mg/month, rather than 0 mg/month or ≥300 mg/month by maintenance or replacement dosing. Findings were robust to numerous sensitivity analyses., Conclusions: Though residual confounding cannot be ruled out in this observational study, findings suggest that IV iron dosing <300 mg/month, as commonly seen with maintenance dosing of 100-200 mg/month, may be a more effective approach to support Hgb than the higher IV iron doses (300-400 mg/month) often given in many European and North American hemodialysis clinics. Alongside studies supporting the safety of IV iron in 100-200 mg/month dose range, these findings help guide the rational dosing of IV iron in anemia management protocols for everyday hemodialysis practice.

Introduction: Turkey has one of the largest treated end-stage renal disease (ESRD) patient populations in Europe (N = 66,711). In 2013, the international Dialysis Outcomes and Practice Patterns Study (DOPPS), a prospective study of hemodialysis (HD) practices and outcomes, initiated data collection in Turkey. Here we provide comparisons of HD patients in DOPPS-Turkey with other international regions and with patients in the Registry of Turkish Nephrology, Dialysis and Transplantation., Methods: DOPPS-Turkey study sites were randomly selected from all Turkish HD units treating ≥25 in-center chronic HD patients. Detailed patient- and facility-level data were collected for 20-30 randomly selected prevalent HD patients per facility., Findings: Demographic and comorbidity profiles for DOPPS-Turkey patients were similar to HD patients overall in the 2013 Turkish Registry Report. In Turkey: diabetes was the most common ESRD cause (37%); arteriovenous fistula use was 83%; mean single pool Kt/V was 1.61. Compared with other international regions, Turkey had the highest mean hemoglobin (11.5 g/dL), ferritin (771 ng/mL), and interdialytic weight gain (3.28%), while Turkey had the lowest mean systolic blood pressure (127 mmHg) and erythropoiesis stimulating agent prescription (57%). Turkish patients also reported the highest depression scores., Discussion: In this first DOPPS-Turkey report, the DOPPS sample agrees well with national Turkish Registry data. Treatment and laboratory data, and patient-reported outcomes, demonstrate similarities and previously unrecognized contrasts to DOPPS findings in Europe, Japan, and North America. Long-term follow-up of these patients will describe how these differences relate to clinical outcomes within Turkey., (© 2016 International Society for Hemodialysis.)

Introduction: There is little comparable information about hemodialysis (HD) practices in low- and middle income countries, including Russia. Evaluation of HD in Russia and its international comparisons could highlight factors providing opportunities for improvement., Methods: We examined treatment patterns for 481 prevalent HD patients in 20 Russian facilities, and compared them to contemporary data for 8512 patients from 311 facilities in seven European countries, Japan, and North America. Data were collected according to the uniform methodology of the Dialysis Outcomes and Practice Patterns Study, phase 5., Findings: Compared to other regions, Russian patients were younger (mean age 53.4 years), had a lower percent of males (52.5%), higher arteriovenous fistula use (89.7%), and longer treatment time (mean: 252 minutes, SD: 37 minutes). Mean single pool Kt/V was 1.49 (SD 0.58). Prescription of dialysate calcium 3.5 mEq/L and aluminum-based phosphate binders were high (15.2% and 17.6% of patients, respectively), while intravenous vitamin D and cinacalcet were low (3.3% and 2.2%, respectively). The percents with parathyroid hormone >600 pg/mL (30.9%) and serum phosphate >1.78 mmol/L (37.7%) were high. Use of erythropoetin stimulating agents (78%) was lower, but hemoglobin, ferritin, and transferrin saturation were generally comparable to North America and Europe., Discussion: These detailed data for hemodialysis in Russia demonstrate that many practice patterns contrasted sharply to those in Europe, Japan, and North America, while other features were similar. Our analysis revealed several positive and some less favorable treatment patterns in Russia that represent opportunities for improving patient care and outcomes., (© 2016 International Society for Hemodialysis.)

Background and Objectives: People receiving hemodialysis to treat kidney failure need a vascular access (a fistula, a graft, or a central venous catheter) to connect to the blood purification machine. Higher rates of access complications are considered the mechanism responsible for the excess mortality observed among catheter or graft users versus fistula users. We tested this hypothesis using mediation analysis., Design, Setting, Participants, & Measurements: We studied incident patients who started hemodialysis therapy from North America, Europe, and Australasia (the Dialysis Outcomes and Practice Patterns Study; 1996-2011). We evaluated the association between access type and time to noninfectious ( e.g. , thrombosis) and infectious complications of the access (mediator model) and the relationship between access type and time-dependent access complications with 6-month mortality from the creation of the first permanent access (outcome model). In mediation analysis, we formally tested whether access complications explain the association between access type and mortality., Results: Of the 6119 adults that we studied (mean age =64 [SD=15] years old; 58% men; 47% patients with diabetes), 50% had a permanent catheter for vascular access, 37% had a fistula, and 13% had a graft. During the 6-month study follow-up, 2084 participants (34%) developed a noninfectious complication of the access, 542 (8.9%) developed an infectious complication, and 526 (8.6%) died. Access type predicted the occurrence of access complications; both access type and complications predicted mortality. The associations between access type and mortality were nearly identical in models excluding and including access complications (hazard ratio, 2.00; 95% confidence interval, 1.55 to 2.58 versus hazard ratio, 2.01; 95% confidence interval, 1.56 to 2.59 for catheter versus fistula, respectively). In mediation analysis, higher mortality with catheters or grafts versus fistulas was not the result of increased rates of access complications., Conclusions: Hemodialysis access complications do not seem to explain the association between access type and mortality. Clinical trials are needed to clarify whether these associations are causal or reflect confounding by underlying disease severity., (Copyright © 2017 by the American Society of Nephrology.)

The United States Renal Data System (USRDS) registry of end-stage renal disease has often been used to study the timing of dialysis initiation, measured by estimated glomerular filtration rate (eGFR) at dialysis initiation. We conducted an observational study and examined how well variables in the USRDS database explain the trends and variation in eGFR at dialysis initiation.We identified 971,481 patients who initiated dialysis between 1995 and 2012 in the USRDS registry.The mean eGFR at dialysis initiation monotonically rose from 7.7 in 1995 to 11.1 in 2009, and then leveled off to 10.9 mL/min/1.73 m in 2012. The trend of rising, then leveling off was similar across all subgroups studied. Substantial variation in eGFR at dialysis initiation was observed, with standard deviation of 4.38 (95% CI: 2.0-18.4). A total of 11.4% of the total variation occurred across physicians and 88.6% within physicians. Adjustment for measured factors only modestly decreased the total variation. Of the total variance, 10.7% was explained by measured patient-level variables and 1.2% by measured physician and other factors, while 9.2% of physician-level variation and 78.9% of patient-level variation remained unexplained. The extent of variation explained by measured variables was similar over the entire study period.The finding that the majority of variation in eGFR at dialysis initiation is unexplained by measured variables casts doubt on how well eGFR serves as a measure for "timing" of dialysis initiation, and it indicates the need to collect more focused data to gain understanding of factors that affect timing of dialysis initiation in the US.

Background: Socioeconomic status (SES) factors such as employment, educational attainment, income, and marital status can affect the health and well-being of the general population and have been associated with the prevalence of chronic kidney disease (CKD). However, no studies to date in Japan have reported on the prognosis of patients with CKD with respect to SES. This study aimed to investigate the influences of employment and education level on mortality and hospitalization among maintenance hemodialysis (HD) patients in Japan., Methods: Data on 7974 HD patients enrolled in Dialysis Outcomes and Practice Patterns Study phases 1-4 (1999-2011) in Japan were analysed. Employment status, education level, demographic data, and comorbidities were abstracted at entry into DOPPS from patient records. Mortality and hospitalization events were collected during follow-up. Patients on dialysis < 120 days at study entry were excluded from the analyses. Cox regression modelled the association between employment and both mortality and hospitalization among patients < 60 years old. The association between education and outcomes was also assessed. The association between patient characteristics and employment among patients < 60 years old was assessed using logistic regression., Results: During a median follow-up of 24.9 months (interquartile range, 18.4-32.0), 10% of patients died and 43% of patients had an inpatient hospitalization. Unemployment was associated with mortality (hazard ratio [HR] = 1.57; 95% confidence interval [CI]: 1.05-2.36) and hospitalization (HR = 1.25; 95% CI: 1.08-1.44). Compared to patients who graduated from university, patients with less than a high school (HS) education and patients who graduated HS with some college tended to have elevated mortality (HR = 1.41; 95% CI, 1.04-1.92 and HR = 1.36; 95% CI: 1.02-1.82, respectively) but were not at risk for increased hospitalizations. Factors associated with unemployment included lower level of education, older age, female gender, longer vintage, and several comorbidities., Conclusions: Employment and education status were inversely associated with mortality in patients on maintenance HD in Japan. Employment but not education was also inversely associated with hospitalizations. After adjustment for comorbidities, the associations with clinical outcomes tended to be stronger for employment than education status.

Background: Cross-sectional health-related quality of life (HR-QOL) measures are associated with mortality in hemodialysis (HD) patients. The impact of changes in HR-QOL on outcomes remains unclear. We describe the association of prior changes in HR-QOL with subsequent mortality among HD patients., Methods: A total of 13 784 patients in the Dialysis Outcomes and Practice Patterns Study had more than one measurement of HR-QOL. The impact of changes between two measurements of the physical (PCS) and mental (MCS) component summary scores of the SF-12 on mortality was estimated with Cox regression., Results: Mean age was 62 years (standard deviation: 14 years); 59% were male and 32% diabetic. Median time between HR-QOL measurements was 12 months [interquartile range (IQR): 11, 14]. Median initial PCS and MCS scores were 37.5 (IQR: 29.4, 46.2) and 46.4 (IQR: 37.2, 54.9); median changes in PCS and MCS scores were -0.2 (IQR: -5.5, 4.7) and -0.1 (IQR: -6.8, 5.9), respectively. The adjusted hazard ratio (HR) for a 5-point decline in HR-QOL score was 1.09 [95% confidence interval (CI): 1.06-1.12] for PCS and 1.05 (95% CI: 1.03-1.08) for MCS. Adjusting for the second QOL score, the change was not associated with mortality: HR = 1.01 (95% CI: 0.98-1.05) for delta PCS and 1.01 (95% CI: 0.98-1.03) for delta MCS. Categorizing the first and second scores as predictors, only the second PCS or MCS score was associated with mortality., Conclusions: In our study, only the most recent HR-QOL score was associated with mortality. Hence, the predictive power of a measurement of HR-QOL is not affected by changes in HR-QOL prior to that measurement; more frequent HR-QOL measurements are needed to improve the prediction of outcomes in HD. Further studies are needed to determine the optimal frequency and appropriate instrument to be used for serial measurements., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

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., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Recent Centers for Medicare & Medicaid Services policies have used dialysis facility practice variation to develop public ratings and adjust payments. In the Dialysis Facility Compare star rating system (DFC SRS), facility-relative rates of performance-based clinical measures varied nearly two-fold for mortality (standardized mortality ratio; 10th/90th percentiles: 0.71, 1.34) and hospitalization (standardized hospitalization ratio; 10th/90th percentiles: 0.64, 1.37), and nearly four-fold for transfusion (standardized transfusion ratio; 10th/90th percentiles: 0.43, 1.65). Medicare claims data (from July of 2014) demonstrate that facility variation for the proportions of patients on hemodialysis hospitalized (10th/90th percentiles: 27%, 50%) and transfused (10th/90th percentiles: 3%, 17%) within 6 months that far exceeds relatively modest recent overall longitudinal trends. DFC SRS-rated facility variation is also substantial for fistula (10th/90th percentiles: 50%, 78%) and catheter use >90 days (10th/90th percentiles: 3%, 19%). By contrast, DFC SRS-rated facility distributions for adult hemodialysis Kt/V>1.2 (10th/90th percentiles: 84%, 97%) and total serum calcium >10.2 mg/dl (median, 1%; 75th/90th percentiles: 3%, 5%) are quite narrow and may be of questionable value. Likewise, variation in the US Dialysis Outcomes and Practice Patterns Study is over two-fold for facility median serum parathyroid hormone (10th/90th percentiles: 290 pg/ml, 629 pg/ml) and ferritin (10th/90th percentiles: 469 ng/ml, 1143 ng/ml) levels, and facility mean treatment time varies by 30 minutes (10th/90th percentiles: 204 minutes, 234 minutes). Rising serum parathyroid hormone and ferritin levels, and generally short dialysis treatment time, represent areas unchecked by existing policy; both overall trends and facility variation in these values may reflect unintended consequences of policy or reimbursement pressures and therefore raise concern. Additionally, outcomes in the transition period from advanced CKD to dialysis remain poor, and policy initiatives and performance accountability in this area remain insufficient. Innovative models of comprehensive care in advanced CKD and the early dialysis period which are more amenable to policy oversight are needed. In summary, facility variation is typically larger than prevailing longitudinal trends, and should not be overlooked. The combination of nationally representative observational databases (e.g., the Dialysis Outcomes and Practice Patterns Study) and ESRD registries can provide policy makers with additional tools to evaluate facility variation, develop policies, and monitor unintended effects., (Copyright © 2016 by the American Society of Nephrology.)

Objective: The malnutrition-inflammation score (MIS) combines ten components to assess nutritional status. Higher MIS has been associated with higher mortality and poorer health-related quality of life (HRQOL) in maintenance hemodialysis (MHD) patients. It is interesting to investigate associations of each component with mortality and patient-reported outcomes (PROs), that is, HRQOL and depression symptoms, and if MIS associations are generalizable for diverse populations. This study assessed associations of MIS and its components with mortality and PROs in an African descent MHD population., Design: Prospective cohort for mortality and cross-sectional design for PROs using data of the Prospective Study of the Prognosis of Chronic Hemodialysis Patients (PROHEMO)., Subjects: A total of 632 MHD patients (92% black or mixed race) treated in Salvador, Brazil., Predictors: MIS (range: 0-30, higher worse) and each of its ten components (range: 0-4, higher worse)., Main Outcome Measures: Mortality, HRQOL using the KDQOL-SF, and depression symptoms using the 20-item Center for Epidemiological Studies Depression Scale., Statistical Analysis: Linear regression for comparing scores and Cox regression for mortality., Results: After extensive adjustments, MIS ≥6 was associated with 52% higher mortality (hazard ratio = 1.52; 95% confidence interval = 1.13-2.05), higher depression symptoms, and poorer HRQOL, including physical, mental, and kidney disease-targeted HRQOL measures. Weight change, comorbidity, muscle wasting, and albumin were the MIS components indicating associations between poor nutrition and higher mortality. By contrast, gastrointestinal symptoms and functional capacity were the MIS components denoting detrimental associations of poorer nutritional status with PROs., Limitation: Causal conclusions are not possible., Conclusions: The PROHEMO results indicate that MIS components associated with mortality are not the same associated with PROs. However, the MIS showed consistent associations with mortality and PROs. These results in a population that were not the target of previous investigations, add support for using tools combining nutritional components, such as MIS, to predict outcomes in MHD populations., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Atrial fibrillation is one of the most common arrhythmias in hemodialysis patients. We evaluated its clinical outcomes among hemodialysis patients with atrial fibrillation in Japan. Using data derived from the Japanese Dialysis Outcomes and Practice Patterns Study, we analyzed backgrounds and outcomes among hemodialysis patients with and without atrial fibrillation in Japan. Among 7002 hemodialysis patients, the prevalence of atrial fibrillation was 5.7% and the incidence was 0.2 per 100 patient-years. Atrial fibrillation was independently associated with all-cause mortality (hazard ratio, 1.32; 95% confidence interval, 1.02-1.71) and cardiovascular events (hazard ratio, 1.39; 95% confidence interval, 1.15-1.68), but not with stroke events (hazard ratio, 0.77; 95% confidence interval, 0.55-1.06) after adjustment for other variables. We conclude that patients with atrial fibrillation experienced higher mortality and more cardiovascular events than did patients without atrial fibrillation, although the risk of stroke was lower than expected., (© 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Objectives: The Coping Strategies Inventory-Short Form (CSI-SF) measures four coping strategies based on 16 items: 4 items each indicating problem- vs. emotion-focused engagement or disengagement. Here we provide the first assessment of reliability and construct validity of the CSI-SF among hemodialysis patients across 13 countries., Methods: The CSI-SF was completed by patients in 9 languages in phase 4 of the Dialysis Outcomes and Practice Patterns Study (2009-11). Cronbach's alpha was used to assess internal consistency. Exploratory and confirmatory factor analyses were applied to assess the factor structure of the CSI-SF by country and language. CSI-SF data were analyzed from 7201 patients (60% male; median age 62.5 [range 18-96] years)., Results: Good internal consistency (α=0.56-0.80) was seen for three scales in English (US, UK, Canada, Australia, New Zealand), German, and Swedish versions. The fourth scale was internally consistent if two items were dropped. In these countries, both exploratory and confirmatory factor analyses indicated a factor structure consistent with the four CSI-SF scales. Other language versions showed a factor structure inconsistent with these four scales., Conclusion: The slightly modified English, German, and Swedish versions of the CSI-SF are reliable and valid instruments for measuring coping strategies in hemodialysis patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The Dialysis Outcomes and Practice Patterns Study (DOPPS) is an international prospective cohort study of the relationships between hemodialysis (HD) care practices and HD patient outcomes. The DOPPS began in 1996, in the United States, and has since expanded to 21 countries, collecting detailed data from >75,000 HD patients, with >200 scientific publications, focused on describing HD practices associated with improved HD patient outcomes. The goal of DOPPS is to help HD patients "live better and live longer." Starting in 2012, the DOPPS was able to expand to all six of the Gulf Cooperation Council (GCC) countries, namely, Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates. The DOPPS study design consists of selecting HD facilities for study participation in each country to represent the different types of HD facilities and geographic regions within each GCC country. Within each study site, HD patients were randomly selected for detailed data collection to represent the HD practices within each participating HD facility. Altogether, 41 HD facilities have participated in the GCC-DOPPS Phase 5 study including 20 facilities from Saudi Arabia, nine from the United Arab Emirates, four each from Kuwait and Oman, two from Qatar, and one from Bahrain. Herein, we provide a detailed description of the study design and methods, data collection, study management, scientific investigator oversight and guidance, and study governance and support for the GCCDOPPS Phase 5 study.

Background: A simple clinical tool to predict cardiovascular disease risk does not exist for haemodialysis patients. The long-term coronary risk Framingham Heart Study Risk score (FRS), although used in this population, may be inadequate. Therefore, we developed separate risk-scores for cardiovascular mortality (CVM) and cardiovascular morbidity & mortality (CVMM) in a Fresenius Medical Care-based haemodialysis patient cohort (AROii)., Methods: Applying a modified FRS approach, we derived and internally validated two-year risk-scores in incident European adult patients randomly assigned to a development (N=4831) or a validation (N=4796) dataset. External validation was conducted in the third Dialysis Outcomes and Practice Patterns Study (DOPPS III) cohort. Additional discrimination comparing to the FRS was performed., Results: The overall two-year CVM and CVMM event rates were 5.0 and 22.6 per 100 person-years respectively. Common risk predictors included increasing age, cardiovascular disease history, primary diabetic nephropathy, low blood pressure, and inflammation. The CVM score was more predictive in AROii (c-statistic 0.72) and in DOPPS III (c-statistic 0.73-0.74) than the CVMM score (c-statistic 0.66-0.67 & 0.63 respectively). The FRS was not predictive of either CVM (c-statistic 0.54) or CVMM (c-statistic 0.56) in AROii., Conclusions: We describe novel, easy-to-apply and interpret CV risk-scores for haemodialysis patients. Our improved cardiovascular prediction performance over traditional (FRS) scores reflected its tailored development and validation in haemodialysis populations, and the integration of non-classical cardiovascular risk factors. The lower expected versus observed CVM and CVMM risk suggests the existence of novel cardiovascular risk factors in this patient population not measured in this study., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

More than 2 million people worldwide are being treated for end-stage kidney disease (ESKD). This Series paper provides an overview of incidence, modality use (in-centre haemodialysis, home dialysis, or transplantation), and mortality for patients with ESKD based on national registry data. We also present data from an international cohort study to highlight differences in haemodialysis practices that affect survival and the experience of patients who rely on this therapy, which is both life-sustaining and profoundly disruptive to their quality of life. Data illustrate disparities in access to renal replacement therapy of any kind and in the use of transplantation or home dialysis, both of which are widely considered preferable to in-centre haemodialysis for many patients with ESKD in settings where infrastructure permits. For most patients with ESKD worldwide who are treated with in-centre haemodialysis, overall survival is poor, but longer in some Asian countries than elsewhere in the world, and longer in Europe than in the USA, although this gap has reduced. Commendable haemodialysis practice includes exceptionally high use of surgical vascular access in Japan and in some European countries, and the use of longer or more frequent dialysis sessions in some countries, allowing for more effective volume management. Mortality is especially high soon after ESKD onset, and improved preparation for ESKD is needed including alignment of decision making with the wishes of patients and families., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

For years, erythropoiesis-stimulating agent (ESA) use among patients on dialysis was much higher in the United States than in Europe or Japan. Sweeping changes to dialysis reimbursement and regulatory policies for ESA in the United States in 2011 were expected to reduce ESA use and hemoglobin levels. We used the Dialysis Outcomes and Practice Patterns Study (DOPPS) data from 7129 patients in 223 in-center hemodialysis facilities (average per month) to estimate and compare time trends in ESA dose and hemoglobin levels among patients on hemodialysis in the United States, Germany, Italy, Spain, the United Kingdom, and Japan. From 2010 to 2013, substantial declines in ESA use and hemoglobin levels occurred in the United States but not in other DOPPS countries. Between August of 2010 and April of 2013, mean weekly ESA dose in the United States decreased 40.4% for black patients and 38.0% for nonblack patients; mean hemoglobin decreased from 11.5 g/dl in black patients and 11.4 g/dl in nonblack patients to 10.6 g/dl in both groups. In 2010 and 2013, adjusted weekly ESA doses per kilogram were 41% and 11% lower, respectively, in patients in Europe and 60% and 18% lower, respectively, in patients in Japan than in nonblack patients in the United States. Adjusted hemoglobin levels in 2010 and 2013 were 0.07 g/dl lower and 0.56 g/dl higher, respectively, in patients in Europe and 0.93 and 0.01 g/dl lower, respectively, in patients in Japan than in nonblack patients in the United States. In conclusion, ESA dosing reductions in the United States likely reflect efforts in response to changes in reimbursement policy and regulatory guidance., (Copyright © 2016 by the American Society of Nephrology.)