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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The risk of death for hemodialysis patients is thought to be highest on the days following the longest interval without dialysis (usually Mondays and Tuesdays); however, existing results are inconclusive. To clarify this we analyzed Dialysis Outcomes and Practice Patterns Study (DOPPS) data of 22,163 hemodialysis patients from the United States, Europe, and Japan. Our study focused on the association between dialysis schedule and day of the week of all-cause, cardiovascular, and noncardiovascular mortality with day-of-week coded as a time-dependent covariate. The models were adjusted for dialysis schedule, age, country, DOPPS phase I or II, and other demographic and clinical covariates, and compared mortality on each day to the 7-day average. Patients on a Monday-Wednesday-Friday (MWF) schedule had elevated all-cause mortality on Mondays, and those on a Tuesday-Thursday-Saturday (TTS) schedule had increased risk of mortality on Tuesdays in all three regions. The association between day-of-week mortality and schedule was generally stronger for cardiovascular than noncardiovascular mortality, and was most pronounced in the United States. Unexpectedly, Japanese patients on a MWF schedule had a higher risk of noncardiovascular mortality on Fridays, and European patients on a TTS schedule experienced an elevated cardiovascular mortality on Saturdays. Thus, future studies are needed to evaluate the influence of practice patterns on schedule-specific mortality and factors that could modulate this effect. [ABSTRACT FROM AUTHOR]

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.)

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.)

Although blood pressure control is a major goal in chronic kidney disease, no worldwide overview of either its achievement or antihypertensive prescriptions is currently available. To evaluate this we compared crude prevalence of uncontrolled blood pressure among 17 cohort studies, including 34 602 individuals with estimated glomerular filtration rate under 60 ml/min/1.73 m 2 and treated hypertension across four continents, and estimated observed to expected prevalence ratios, adjusted for potential confounders. Crude prevalence of blood pressure of 140/90 mm Hg or more varied from 28% to 61% and of blood pressure of 130/80 or more from 54% to 84%. Adjusted prevalence ratios indicated poorer hypertension control than expected in cohorts from European countries, India, and Uruguay, and better control in patients from North American and high-income Asian countries. Four antihypertensive drug classes or more were prescribed to more than 30% of participants in North American and some European cohorts, but this practice was less common elsewhere. Renin angiotensin-aldosterone system inhibitors were the most common antihypertensive drugs, prescribed for 54% to 91% of cohort participants. Differences for other drug classes were much stronger, ranging from 11% to 79% for diuretics, 22% to 70% for beta-blockers, and 27% to 75% for calcium-channel blockers. The confounders studied explain only a part of the international variation in blood pressure control among individuals with chronic kidney disease. Thus, considerable heterogeneity in prescription patterns worldwide calls for further investigation into the impact of different approaches on patient outcomes., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

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.

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.

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: 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.)

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.)

Although mortality risk scores for chronic hemodialysis (HD) patients should have an important role in clinical decision-making, those currently available have limited applicability, robustness, and generalizability. Here we applied a modified Framingham Heart Study approach to derive 1- and 2-year all-cause mortality risk scores using a 11,508 European incident HD patient database (AROii) recruited between 2007 and 2009. This scoring model was validated externally using similar-sized Dialysis Outcomes and Practice Patterns Survey (DOPPS) data. For AROii, the observed 1- and 2-year mortality rates were 13.0 (95% confidence interval (CI; 12.3-13.8)) and 11.2 (10.4-12.1)/100 patient years, respectively. Increasing age, low body mass index, history of cardiovascular disease or cancer, and use of a vascular access catheter during baseline were consistent predictors of mortality. Among baseline laboratory markers, hemoglobin, ferritin, C-reactive protein, serum albumin, and creatinine predicted death within 1 and 2 years. When applied to the DOPPS population, the predictive risk score models were highly discriminatory, and generalizability remained high when restricted by incidence/prevalence and geographic location (C-statistics 0.68-0.79). This new model offers improved predictive power over age/comorbidity-based models and also predicted early mortality (C-statistic 0.71). Our new model delivers a robust and reproducible mortality risk score, based on readily available clinical and laboratory data.

Context: Viral/bacterial infection is proposed as a trigger for the autoimmune thyroid diseases (AITD): Graves' disease (GD) and Hashimoto's thyroiditis (HT). Previous studies in European Caucasian AITD subjects found higher birth rates in the autumn/winter, suggesting those born in the autumn/winter experience increased viral/bacterial exposure after birth, impacting upon immune system development and predisposing to AITD later in life., Objective: Month of birth effects were investigated in three independent European Caucasian AITD datasets., Design: Variation in GD and HT onset was compared across months and seasons, with fluctuations across all 12 months analyzed using a Walter-Elwood test., Setting: The study was conducted at a research laboratory., Patients: National UK Caucasian AITD Case Control Collection (2746 GD and 502 HT compared with 1 423 716 UK births), National UK Caucasian GD Family Collection (239 GD and 227 unaffected siblings), and OXAGEN AITD Caucasian Family Collection (885 GD, 717 HT, and 794 unaffected siblings of European Caucasian decent)., Main Outcome Measures: Case-control and family-based association studies were measured., Results: No consistent month of birth effects were detected in GD females or males across all three collections. In HT females from the OXAGEN AITD Caucasian Family Collection, slightly higher birth rates were detected in autumn (Walter's test statistic = 7.47, P = .024) however, this was not seen in the HT females from the case-control cohort., Conclusion: Our results suggest in UK/Northern European Caucasian GD subjects, month of birth does not impact on AITD development. Although some month of birth effects for HT females in one collection cannot be excluded, only further work in larger European Caucasian AITD collections can confirm these effects.

Purpose: Catheters are associated with worse clinical outcomes than fistulas and grafts in hemodialysis (HD) patients. One potential modifier of patient vascular access (VA) use is patient preference for a particular VA type. The purpose of this study is to identify predictors of patient VA preference that could be used to improve patient care., Methods: This study uses a cross-sectional sample of data from the Dialysis Outcomes and Practice Patterns Study (DOPPS 3, 2005-09), that includes 3815 HD patients from 224 facilities in 12 countries. Using multivariable models we measured associations between patient demographic and clinical characteristics, previous catheter use and patient preference for a catheter., Results: Patient preference for a catheter varied across countries, ranging from 1% of HD patients in Japan and 18% in the United States, to 42% to 44% in Belgium and Canada. Preference for a catheter was positively associated with age (adjusted odds ratio per 10 years=1.14; 95% CI=1.02-1.26), female sex (OR 1.49; 95% CI=1.15-1.93), and former (OR=2.61; 95% CI=1.66-4.12) or current catheter use (OR=60.3; 95% CI=36.5-99.8); catheter preference was inversely associated with time on dialysis (OR per three years=0.90; 95% CI=0.82-0.97)., Conclusions: Considerable variation in patient VA preference was observed across countries, suggesting that patient VA preference may be influenced by sociocultural factors and thus could be modifiable. Catheter preference was greatest among current and former catheter users, suggesting that one way to influence patient VA preference may be to avoid catheter use whenever possible.

KDOQI practice guidelines recommend predialysis blood pressure <140/90 mm Hg; however, most prior studies had found elevated mortality with low, not high, systolic blood pressure. This is possibly due to unmeasured confounders affecting systolic blood pressure and mortality. To lessen this bias, we analyzed 24,525 patients by Cox regression models adjusted for patient and facility characteristics. Compared with predialysis systolic blood pressure of 130-159 mm Hg, mortality was 13% higher in facilities with 20% more patients at systolic blood pressure of 110-129 mm Hg and 16% higher in facilities with 20% more patients at systolic blood pressure of ≥160 mm Hg. For patient-level systolic blood pressure, mortality was elevated at low (<130 mm Hg), not high (≥180 mm Hg), systolic blood pressure. For predialysis diastolic blood pressure, mortality was lowest at 60-99 mm Hg, a wide range implying less chance to improve outcomes. Higher mortality at systolic blood pressure of <130 mm Hg is consistent with prior studies and may be due to excessive blood pressure lowering during dialysis. The lowest risk facility systolic blood pressure of 130-159 mm Hg indicates this range may be optimal, but may have been influenced by unmeasured facility practices. While additional study is needed, our findings contrast with KDOQI blood pressure targets, and provide guidance on optimal blood pressure range in the absence of definitive clinical trial data.

Background: Psychosocial factors are associated with clinical outcomes in patients with end-stage renal disease. It is not known if self-reported depression and quality of life influence the likelihood of being wait-listed and receiving a transplant., Methods: Prevalent cross section of 18- to 65-year-old hemodialysis (HD) patients in the USA (N = 2033) and seven European countries (N = 4350) from the Dialysis Outcomes and Practice Patterns Study phase II and III was analyzed. Wait-listed patients (N = 1838) were followed until kidney transplantation. Self-reported depressive symptoms were assessed by the Center for Epidemiologic Studies-Depression scale, 10-item version (CES-D) and health-related quality of life (HR-QoL) by the Kidney Disease Quality of Life Short Form 12 scale Physical Component Score (PCS)., Results: At study entry, 27% (USA) to 53% (UK) of patients were wait-listed in participating countries. Variables associated with lower odds of being on the waiting list included worse HR-QoL, more severe depressive symptoms, older age, fewer years of education, lower serum albumin, lower hemoglobin, shorter time on dialysis and presence of multiple comorbid conditions. Among wait-listed patients, significantly lower transplantation rates were seen for females, blacks, patients having prior transplantation and multiple comorbid conditions but not PCS or CES-D., Conclusions: Fewer depressive symptoms and better HR-QoL are associated with being on the waiting list in prevalent HD patients but not with receiving a kidney transplant among wait-listed dialysis patients. Regular assessment of subjective well-being may help identify patients with reduced access to wait-listing and kidney transplantation.

Background and Objectives: Measurement of C-reactive protein (CRP) levels remains uncommon in North America, although it is now routine in many countries. Using Dialysis Outcomes and Practice Patterns Study data, our primary aim was to evaluate the value of CRP for predicting mortality when measured along with other common inflammatory biomarkers., Design, Setting, Participants, & Measurements: We studied 5061 prevalent hemodialysis patients from 2005 to 2008 in 140 facilities routinely measuring CRP in 10 countries. The association of CRP with mortality was evaluated using Cox regression. Prediction of 1-year mortality was assessed in logistic regression models with differing adjustment variables., Results: Median baseline CRP was lower in Japan (1.0 mg/L) than other countries (6.0 mg/L). CRP was positively, monotonically associated with mortality. No threshold below which mortality rate leveled off was identified. In prediction models, CRP performance was comparable with albumin and exceeded ferritin and white blood cell (WBC) count based on measures of model discrimination (c-statistics, net reclassification improvement [NRI]) and global model fit (generalized R(2)). The primary analysis included age, gender, diabetes, catheter use, and the four inflammatory markers (omitting one at a time). Specifying NRI ≥5% as appropriate reclassification of predicted mortality risk, NRI for CRP was 12.8% compared with 10.3% for albumin, 0.8% for ferritin, and <0.1% for WBC., Conclusions: These findings demonstrate the value of measuring CRP in addition to standard inflammatory biomarkers to improve mortality prediction in hemodialysis patients. Future studies are indicated to identify interventions that lower CRP and to identify whether they improve clinical outcomes.

Background and Objectives: Hyperuricemia is associated with hypertension, coronary artery disease, and chronic kidney disease. However, there are no specific data on the relationship of uric acid to cardiovascular disease in the chronic hemodialysis setting., Design, Setting, Participants, & Measurements: Data from 5827 patients on chronic hemodialysis from six countries affiliated with the Dialysis Outcomes and Practice Patterns Study (DOPPS) were analyzed. All laboratory data were based upon the initial cross-section of patients in DOPPS I and II. Cox regression was used to calculate the hazard ratio (HR) of all-cause and cardiovascular (CV) mortality with adjustments for case-mix including 14 classes of comorbidity., Results: There were no clinically significant differences in baseline characteristics between those who had measured uric acid (n = 4637) and those who did not (n = 1190). Uric acid level was associated with lower all-cause mortality (HR: 0.95, 95% confidence interval [CI]: 0.90 to 1.00 per 1 mg/dl higher uric acid level) and CV mortality (HR: 0.92, 95% CI: 0.86 to 0.99). When analyzed as a dichotomous variable, the adjusted HR at uric acid ≤8.2 mg/dl compared with >8.2 mg/dl was 1.24 (95% CI: 1.03 to 1.49) for all-cause mortality and 1.54 (95% CI: 1.15 to 2.07) for CV mortality., Conclusions: Higher uric acid levels were associated with lower risk of all-cause and CV mortality in the hemodialysis population. These results are in contrast to the association of hyperuricemia with higher cardiovascular risk in the general population and should be the subject of further research.

Background: Abnormalities in serum calcium, phosphorus, and parathyroid hormone (PTH) concentrations are common in patients with chronic kidney disease and have been associated with increased morbidity and mortality. No clinical trials have been conducted to clearly identify categories of calcium, phosphorus, and PTH levels associated with the lowest mortality risk. Current clinical practice guidelines are based largely on expert opinions, and clinically relevant differences exist among guidelines across countries. We sought to describe international trends in calcium, phosphorus, and PTH levels during 10 years and identify mortality risk categories in the Dialysis Outcomes and Practice Patterns Study (DOPPS), an international study of hemodialysis practices and associated outcomes., Study Design: Prospective cohort study., Participants: 25,588 patients with end-stage renal disease on hemodialysis therapy for longer than 180 days at 925 facilities in DOPPS I (1996-2001), DOPPS II (2002-2004), or DOPPS III (2005-2007)., Predictors: Serum calcium, albumin-corrected calcium (Ca(Alb)), phosphorus, and PTH levels., Outcomes: Adjusted hazard ratios for all-cause and cardiovascular mortality calculated using Cox models., Results: Distributions of mineral metabolism markers differed across DOPPS countries and phases, with lower calcium and phosphorus levels observed in the most recent phase of DOPPS. Survival models identified categories with the lowest mortality risk for calcium (8.6 to 10.0 mg/dL), Ca(Alb) (7.6 to 9.5 mg/dL), phosphorus (3.6 to 5.0 mg/dL), and PTH (101 to 300 pg/mL). The greatest risk of mortality was found for calcium or Ca(Alb) levels greater than 10.0 mg/dL, phosphorus levels greater than 7.0 mg/dL, and PTH levels greater than 600 pg/mL and in patients with combinations of high-risk categories of calcium, phosphorus, and PTH., Limitations: Because of the observational nature of DOPPS, this study can only indicate an association between mineral metabolism categories and mortality., Conclusions: Our results provide important information about mineral metabolism trends in hemodialysis patients in 12 countries during a decade. The risk categories identified in the DOPPS cohort may be relevant to efforts at international harmonization of existing clinical guidelines for mineral metabolism.