Serum Phosphorus Level Rises in US Hemodialysis Patients Over the Past Decade: A DOPPS Special Report.

Mineral bone disorder (MBD) is a frequent consequence of chronic kidney disease, more so in patients with kidney failure treated by kidney replacement therapy. Despite the wide availability of interventions to control serum phosphate and parathyroid hormone levels, unmet gaps remain on optimal targets and best practices, leading to international practice pattern variations over time. In this Special Report, we describe international trends from the Dialysis Outcomes and Practice Patterns Study (DOPPS) for MBD biomarkers and treatments from 2002-2021, including data from a group of 7 European countries (Belgium, France, Germany, Italy, Spain, Sweden, United Kingdom), Japan, and the United States. From 2002-2012, mean phosphate levels declined in Japan (5.6 to 5.2 mg/dL), Europe (5.5 to 4.9 mg/dL), and the United States (5.7 to 5.0 mg/dL). Since then, levels rose in the United States (to mean 5.6 mg/dL, 2021), were stable in Japan (5.3 mg/dL), and declined in Europe (4.8 mg/dL). In 2021, 52% (United States), 27% (Europe), and 39% (Japan) had phosphate >5.5 mg/dL. In the United States, overall phosphate binder use was stable (80%-84% over 2015-2021), and parathyroid hormone levels rose only modestly. Although these results potentially stem from pervasive knowledge gaps in clinical practice, the noteworthy steady increase in serum phosphate in the United States over the past decades may be consequential to patient outcomes, an uncertainty that hopefully will soon be addressed by ongoing clinical trials. The DOPPS will continue to monitor international trends as new interventions and strategies ensue for MBD management in chronic kidney disease.

Serum Biomarkers of Iron Stores Are Associated with Increased Risk of All-Cause Mortality and Cardiovascular Events in Nondialysis CKD Patients, with or without Anemia.

BACKGROUND: Approximately 30%-45% of patients with nondialysis CKD have iron deficiency. Iron therapy in CKD has focused primarily on supporting erythropoiesis. In patients with or without anemia, there has not been a comprehensive approach to estimating the association between serum biomarkers of iron stores, and mortality and cardiovascular event risks. METHODS: The study included 5145 patients from Brazil, France, the United States, and Germany enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study, with first available transferrin saturation (TSAT) and ferritin levels as exposure variables. We used Cox models to estimate hazard ratios (HRs) for all-cause mortality and major adverse cardiovascular events (MACE), with progressive adjustment for potentially confounding variables. We also used linear spline models to further evaluate functional forms of the exposure-outcome associations. RESULTS: Compared with patients with a TSAT of 26%-35%, those with a TSAT ≤15% had the highest adjusted risks for all-cause mortality and MACE. Spline analysis found the lowest risk at TSAT 40% for all-cause mortality and MACE. Risk of all-cause mortality, but not MACE, was also elevated at TSAT ≥46%. Effect estimates were similar after adjustment for hemoglobin. For ferritin, no directional associations were apparent, except for elevated all-cause mortality at ferritin ≥300 ng/ml. CONCLUSIONS: Iron deficiency, as captured by TSAT, is associated with higher risk of all-cause mortality and MACE in patients with nondialysis CKD, with or without anemia. Interventional studies evaluating the effect on clinical outcomes of iron supplementation and therapies for alternative targets are needed to better inform strategies for administering exogenous iron.

A real-world longitudinal study of anemia management in non-dialysis-dependent chronic kidney disease patients: a multinational analysis of CKDopps.

Previously lacking in the literature, we describe longitudinal patterns of anemia prescriptions for non-dialysis-dependent chronic kidney disease (NDD-CKD) patients under nephrologist care. We analyzed data from 2818 Stage 3-5 NDD-CKD patients from Brazil, Germany, and the US, naïve to anemia medications (oral iron, intravenous [IV] iron, or erythropoiesis stimulating agent [ESA]) at enrollment in the CKDopps. We report the cumulative incidence function (CIF) of medication initiation stratified by baseline characteristics. Even in patients with hemoglobin (Hb) < 10 g/dL, the CIF at 12 months for any anemia medication was 40%, and 28% for ESAs. Patients with TSAT < 20% had a CIF of 26% and 6% for oral and IV iron, respectively. Heart failure was associated with earlier initiation of anemia medications. IV iron was prescribed to < 10% of patients with iron deficiency. Only 40% of patients with Hb < 10 g/dL received any anemia medication within a year. Discontinuation of anemia treatment was very common. Anemia treatment is initiated in a limited number of NDD-CKD patients, even in those with guideline-based indications to treat. Hemoglobin trajectory and a history of heart failure appear to guide treatment start. These results support the concept that anemia is sub-optimally managed among NDD-CKD patients in the real-world setting.

Associations of Hemoglobin Levels With Health-Related Quality of Life, Physical Activity, and Clinical Outcomes in Persons With Stage 3-5 Nondialysis CKD.

OBJECTIVE: Conflicting findings and knowledge gaps exist regarding links between anemia, physical activity, health-related quality of life (HRQOL), chronic kidney disease (CKD) progression, and mortality in moderate-to-advanced CKD. Using the CKD Outcomes and Practice Patterns Study, we report associations of hemoglobin (Hgb) with HRQOL and physical activity, and associations of Hgb and physical activity with CKD progression and mortality in stage 3-5 nondialysis (ND)-CKD patients. DESIGN AND METHODS: Prospectively collected data were analyzed from 2,121 ND-CKD stage 3-5 patients, aged ≥18 years, at 43 nephrologist-run US and Brazil CKD Outcomes and Practice Patterns Study-participating clinics. Cross-sectional associations were assessed of Hgb levels with HRQOL and physical activity levels (from validated Kidney Disease Quality of Life Instrument and Rapid Assessment of Physical Activity surveys). CKD progression (first of ≥40% estimated glomerular filtration rate [eGFR] decline, eGFR<10 mL/min/1.73 m2, or end-stage kidney disease) and all-cause mortality with Hgb and physical activity levels were also evaluated. Linear, logistic, and Cox regression analyses were adjusted for country, demographics, smoking, eGFR, serum albumin, very high proteinuria, and 13 comorbidities. RESULTS: HRQOL was worse, with severe anemia (Hgb<10 g/dL), but also evident for mild/moderate anemia (Hgb 10-12 g/dL), relative to Hgb>12 g/dL. Odds of being highly physically active were substantially greater at Hgb>10.5 g/dL. Lower Hgb was strongly associated with greater CKD progression and mortality, even after extensive adjustment. Physical inactivity was strongly associated with greater mortality and weakly associated with CKD progression. Possible residual confounding is a limitation. CONCLUSION: This multicenter international study provides real-world observational evidence for greater HRQOL, physical activity, lower CKD progression, and greater survival in ND-CKD patients with Hgb levels >12 g/dL, exceeding current treatment guideline recommendations. These findings help inform future studies aimed at understanding the impact of new anemia therapies and physical activity regimens on improving particular dimensions of ND-CKD patient well-being and clinical outcomes.

Coping with fluid restriction and the quality of life in hemodialysis patients with very low or no daily urine output.

PURPOSE: Fluid restriction is crucial to prevent circulatory overload in maintenance hemodialysis (MHD) patients with very low urine volume, but fluid restriction may result in psychological distress. We studied MHD patients with urine volume ≤ 200 ml/day to investigate if their acceptance of fluid restriction was associated with their health-related quality of life (HRQOL). METHODS: Cross-sectional study of 271 Brazilian adult MHD patients enrolled in the Prospective Study of the Prognosis of Chronic Hemodialysis Patients (PROHEMO). To assess the acceptance of fluid restriction, patients were asked about the extent of feeling bothered by living on this restriction. The KDQOL was used to determine HRQOL scores. Higher scores indicate better HRQOL with differences of >3.0 points considered clinically significant. RESULTS: 52.4% reported being "moderately to extremely" bothered by fluid restriction and had lower scores for all HRQOL scales than patients less bothered by fluid restriction. The largest covariate-adjusted differences in HRQOL were 19.5 for emotional role (p<0.001), 15.1 for emotional well-being (p<0.001), and 14.1 for vitality (p<0.001). Adjusted differences were larger for mental component (7.53 points, p<0.001) than for physical component (2.07, p = 0.075) summaries. CONCLUSIONS: These results indicate that MHD patients with a lower level of acceptance of fluid restriction have poorer HRQOL, particularly in mental domains of HRQOL. The high prevalence of poor acceptance of fluid restriction in the present study underscores the need for interventions to improve acceptance of fluid restriction and determine if such interventions improve HRQOL of MHD patients with very low urine volume.

The chronic kidney disease outcomes and practice patterns study Brazil (CKDopps-Brazil): design, data and methodology.

INTRODUCTION: The chronic kidney disease outcomes and practice patterns study (CKDopps) is an international observational, prospective, cohort study involving patients with chronic kidney disease (CKD) stages 3-5 [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, with a major focus upon care during the advanced CKD period (eGFR < 30 ml/min/1.73 m2)]. During a 1-year enrollment period, each one of the 22 selected clinics will enroll up to 60 advanced CKD patients (eGFR < 30 ml/min/1.73 m2 and not dialysis-dependent) and 20 earlier stage CKD patients (eGFR between 30-59 ml/min/1.73 m2). EXCLUSION CRITERIA: age < 18 years old, patients on chronic dialysis or prior kidney transplant. The study timeline include up to one year for enrollment of patients at each clinic starting in the end of 2013, followed by up to 2-3 years of patient follow-up with collection of detailed longitudinal patient-level data, annual clinic practice-level surveys, and patient surveys. Analyses will apply regression models to evaluate the contribution of patient-level and clinic practice-level factors to study outcomes, and utilize instrumental variable-type techniques when appropriate. CONCLUSION: Launching in 2013, CKDopps Brazil will study advanced CKD care in a random selection of nephrology clinics across Brazil to gain understanding of variation in care across the country, and as part of a multinational study to identify optimal treatment practices to slow kidney disease progression and improve outcomes during the transition period to end-stage kidney disease.

The chronic kidney disease outcomes and practice patterns study Brazil (CKDopps-Brazil): Design, data and methodology / Estudo dos desfechos de doenca renal cronica e padroes da pratica atual - Brasil (CKDopps-Brazil): Desenho, dados e metodologia

Introduction: The chronic kidney disease outcomes and practice patterns study (CKDopps) is an international observational, prospective, cohort study involving patients with chronic kidney disease (CKD) stages 3-5 [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, with a major focus upon care during the advanced CKD period (eGFR < 30 ml/min/1.73 m2)]. During a 1-year enrollment period, each one of the 22 selected clinics will enroll up to 60 advanced CKD patients (eGFR < 30 ml/min/1.73 m2 and not dialysis-dependent) and 20 earlier stage CKD patients (eGFR between 30-59 ml/min/1.73 m2). Exclusion criteria: age < 18 years old, patients on chronic dialysis or prior kidney transplant. The study timeline include up to one year for enrollment of patients at each clinic starting in the end of 2013, followed by up to 2-3 years of patient follow-up with collection of detailed longitudinal patient-level data, annual clinic practice-level surveys, and patient surveys. Analyses will apply regression models to evaluate the contribution of patient-level and clinic practice-level factors to study outcomes, and utilize instrumental variable-type techniques when appropriate. Conclusion: Launching in 2013, CKDopps Brazil will study advanced CKD care in a random selection of nephrology clinics across Brazil to gain understanding of variation in care across the country, and as part of a multinational study to identify optimal treatment practices to slow kidney disease progression and improve outcomes during the transition period to end-stage kidney disease. .

Introdução: O Estudo de padrões da prática e desfechos das doenças renais crônicas (CKDopps) é um estudo internacional observacional, prospectivo, com uma coorte composta de pacientes com doenças renais crônicas (DRC) nos estágios 3-5 [taxa de filtração glomerular estimada (eGFR) < 60 ml/min/1,73 m2, com um grande foco sobre o tratamento durante o período de doença renal crônica avançada (eGFR < 30 ml/min/1,73 m2)]. Durante o período de recrutamento de participantes, de 1 ano, cada uma das 22 clínicas selecionadas inscreverá até 60 pacientes com DRC avançada (eGFR < 30 ml/min/1,73 m2 e não dependente de diálise) e 20 pacientes com DRC em estágios anteriores (eGFR entre 30-59 ml/min/1,73 m2). Os critérios de exclusão são: idade < 18 anos; pacientes em diálise crônica ou transplante de rim prévio. O cronograma de estudo inclui até um ano para a inscrição dos pacientes em cada clínica a partir do final de 2013, sendo então acompanhados por 2-3 anos, com coleta de dados longitudinais detalhados dos pacientes, pesquisas anuais dos níveis da prática na clínica e levantamentos de informação dos pacientes. As análises aplicarão modelos de regressão para avaliar a contribuição de fatores relacionados à clínica e aos próprios pacientes para estudar os desfechos, e utilizar técnicas do tipo: variável instrumental, quando apropriado. Conclusão: Lançado em 2013, o CKDopps-Brasil, avaliará o tratamento de DRC avançada em uma seleção aleatória de clínicas de nefrologia em todo o Brasil para entender como o tratamento varia em nosso país, e como parte de um estudo multinacional para identificar as práticas de tratamento ideal para retardar ...

Prevalence and management of anemia in hemodialysis patients in a Brazilian population of predominantly African descent.

BACKGROUND/OBJECTIVE: Findings from the international DOPPS indicated a rise in hemoglobin levels for patients on maintenance hemodialysis (MHD) for more than 180 days across many countries with more than 60% with hemoglobin ≥11 g/dl. However, the situation of anemia control for a large contingent of the hemodialysis population remains unknown. Studies in the United States indicate that hemoglobin level is lower for African Americans on MHD, but studies in other populations of African descent are lacking. We investigated the prevalence of, and associated factors for, hemoglobin <11 g/dl in MHD patients from the Brazilian city with the largest proportion of African descendants outside Africa. METHODS: Cross-sectional study of 1,263 MHD patients enrolled in the Prospective Study of the Prognosis of Chronic Hemodialysis Patients (PROHEMO) in Salvador, Brazil 2005-2009. RESULTS: 88.0% black or mixed race; age 49.0 ± 14.7 years; 96.6% receiving erythropoietin, median = 6,000 units/week. In patients on MHD for more than 180 days, 67.4% had hemoglobin <11 g/dl. Factors associated with hemoglobin<11 g/dl were MHD by catheter (odds ratio (OR) = 3.03, 95% confidence interval (CI) = 1.43-6.42), hospitalization in prior 3 months (OR = 2.14, 95% CI = 1.20-3.83), transferrin saturation <20% (OR = 1.49, 95% CI = 1.05-2.12) and higher malnutrition-inflammation score (OR = 1.58 per each log-transformed unit, 95% CI = 1.14-2.19). CONCLUSIONS: The results suggest that iron deficiency, insufficient erythropoietin dose, catheter use, malnutrition-inflammation, and problems associated with hospitalization are explanations for the high prevalence of hemoglobin below the guideline target in MHD patients from a large African descent Brazilian population. These results have implications for understanding the lower hemoglobin concentration in MHD populations of African descent.

Phosphate binder use and mortality among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS): evaluation of possible confounding by nutritional status.

BACKGROUND: Poor nutritional status and both hyper- and hypophosphatemia are associated with increased mortality in maintenance hemodialysis (HD) patients. We assessed associations of phosphate binder prescription with survival and indicators of nutritional status in maintenance HD patients. STUDY DESIGN: Prospective cohort study (DOPPS [Dialysis Outcomes and Practice Patterns Study]), 1996-2008. SETTING & PARTICIPANTS: 23,898 maintenance HD patients at 923 facilities in 12 countries. PREDICTORS: Patient-level phosphate binder prescription and case-mix-adjusted facility percentage of phosphate binder prescription using an instrumental-variable analysis. OUTCOME: All-cause mortality. RESULTS: Overall, 88% of patients were prescribed phosphate binders. Distributions of age, comorbid conditions, and other characteristics showed small differences between facilities with higher and lower percentages of phosphate binder prescription. Patient-level phosphate binder prescription was associated strongly at baseline with indicators of better nutrition, ie, higher values for serum creatinine, albumin, normalized protein catabolic rate, and body mass index and absence of cachectic appearance. Overall, patients prescribed phosphate binders had 25% lower mortality (HR, 0.75; 95% CI, 0.68-0.83) when adjusted for serum phosphorus level and other covariates; further adjustment for nutritional indicators attenuated this association (HR, 0.88; 95% CI, 0.80-0.97). However, this inverse association was observed for only patients with serum phosphorus levels ≥3.5 mg/dL. In the instrumental-variable analysis, case-mix-adjusted facility percentage of phosphate binder prescription (range, 23%-100%) was associated positively with better nutritional status and inversely with mortality (HR for 10% more phosphate binders, 0.93; 95% CI, 0.89-0.96). Further adjustment for nutritional indicators reduced this association to an HR of 0.95 (95% CI, 0.92-0.99). LIMITATIONS: Results were based on phosphate binder prescription; phosphate binder and nutritional data were cross-sectional; dietary restriction was not assessed; observational design limits causal inference due to possible residual confounding. CONCLUSIONS: Longer survival and better nutritional status were observed for maintenance HD patients prescribed phosphate binders and in facilities with a greater percentage of phosphate binder prescription. Understanding the mechanisms for explaining this effect and ruling out possible residual confounding require additional research.

Assessment of the psychological burden associated with pruritus in hemodialysis patients using the kidney disease quality of life short form.

PURPOSE: To assess whether depression symptoms, poor sleep and dry skin bother explain association between pruritus and the burden of kidney disease in maintenance hemodialysis (MHD) patients. METHODS: Cross-sectional study of 980 patients from a prospective study in dialysis units of Salvador, Brazil (PROHEMO). The Kidney Disease Quality of Life Short Form was used to determine scores of kidney disease burden (KDB) and sleep with higher scores indicating lower perceived burden and better sleep quality, respectively. The Center for Epidemiological Studies Depression Scale was used for depression symptoms. RESULTS: Prevalence of severe pruritus (very much or extreme) was 19.4%. Significantly (P < 0.001) lower mean KDB score by 11.44 points was observed for patients with severe pruritus (34.18 ± 27.51) than for those with no pruritus (45.62 ± 30.73). Severe pruritus was associated with poorer sleep quality, higher odds of dry skin bother and higher depression symptoms score. Association of pruritus with KDB score was virtually eliminated after adjustment for sleep, dry skin bother and depression symptoms. CONCLUSIONS: This study shows strong associations of severe pruritus with higher depression symptoms, poorer sleep and dry skin bother among MHD patients. The results support special attention to MHD patients with pruritus who often face high psychological burden.

Handgrip strength as a simple indicator of possible malnutrition and inflammation in men and women on maintenance hemodialysis.

OBJECTIVE: To assess the validity of handgrip strength (HGS) as a simple screening instrument for malnutrition and inflammation in patients on maintenance hemodialysis (MHD) by correlating it with malnutrition-inflammation score (MIS). DESIGN: Cross-sectional analysis of the Prospective Study of the Prognosis in Chronic Hemodialysis Patients (PROHEMO). SETTING: Satellite dialysis units in the city of Salvador, Brazil. PATIENTS: The sample included 274 men and 162 women on MHD. MAIN PREDICTOR VARIABLE: HGS was chosen as the main predictor variable in this study. MAIN OUTCOME MEASURE: An MIS ≥6. RESULTS: As compared with men, women were found to have lower HGS values (19.38 ± 6.48 kg vs. 29.07 ± 8.67 kg; P < .001) and higher MIS (6.38 ± 3.84 vs. 5.57 ± 3.39; P = .032). HGS was found to be inversely correlated with MIS among women (Spearman's ρ = -.360; P < .001) as well as men (Spearman's ρ = -0.384; P < .001); this inverse correlation was observed in patients with and without diabetes, different racial groups, younger and older subjects, incident (<3 months) and prevalent patients, in the case of both genders. Among both men and women, every one standard deviation lower of HGS was associated with more than two-fold higher odds for MIS ≥6, after adjusting for age, race, duration of dialysis, and Kt/V. These associations remained statistically significant after more extensive adjustments. The optimized cutoff point of HGS for MIS ≥6 was 28.3 kg for men (sensitivity = 70.0%; specificity = 66.0%) and 23.4 kg for women (sensitivity = 87.0%; specificity = 43.0%). CONCLUSIONS: Lower HGS values were independently associated with higher MIS among patients on MHD across several subgroups. These results suggest that HGS is a valid screening instrument for malnutrition and inflammation in patients on MHD.

Independent and joint associations of nutritional status indicators with mortality risk among chronic hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

OBJECTIVE: To consider the Kidney Disease Outcomes Quality Initiative recommendation of using multiple nutritional measurements for patients on maintenance dialysis, we explored data for independent and joint associations of nutritional indicators with mortality risk among maintenance hemodialysis patients treated in 12 countries. SETTING: Dialysis units in seven European countries, the United States, Canada, Australia, New Zealand, and Japan. MAIN OUTCOME: Mortality risk. METHODS: We conducted a prospective cohort study of 40,950 patients from phases I to III of the Dialysis Outcomes and Practice Patterns Study (1996-2008). Independent and joint effects (interactions) of nutritional indicators (serum creatinine, serum albumin, normalized protein catabolic rate, body mass index [BMI]) on mortality risk were assessed by Cox regression with adjustments for demographics, years on dialysis, and comorbidities. RESULTS: Important variations in nutritional indicators were seen by country and patient characteristics. Poorer nutritional status assessed by each indicator was independently associated with higher mortality risk across regions. Significant multiplicative interactions (each p < or = 0.01) between indicators were also observed. For example, by using patients with serum creatinine 7.5-10.5 mg/dL and BMI 21-25 kg/m(2) as referent, BMI <21 kg/m(2) was associated with lower mortality risk among patients with creatinine >10.5 mg/dL (relative risk = 0.68) but with higher mortality risk among those with creatinine <7.5 mg/dL (relative risk = 1.38). The association of lower albumin concentration with higher mortality risk was stronger for patients with lower BMI or lower creatinine. CONCLUSION: The joint effects of nutritional indicators on mortality indicate the need to use multiple measurements when assessing the nutritional status of hemodialysis patients.

Lack of appetite in haemodialysis patients--associations with patient characteristics, indicators of nutritional status and outcomes in the international DOPPS.

BACKGROUND: Identification of haemodialysis patients with problems related to lack of appetite should help prevent adverse outcomes. We studied whether a single question about being bothered by lack of appetite within the prior 4 weeks is related to nutritional status, inflammation and risks of death and hospitalization. Additionally, we assessed associations of lack of appetite with depression, dialysis dose and length of haemodialysis. METHODS: This study is an analysis of baseline and longitudinal data from 14 406 patients enrolled in the Dialysis Outcomes and Practice Pattern Study. Cox regression was used to assess whether the degree (not, somewhat, moderately, very much, extremely) that patients were bothered by lack of appetite is an independent predictor of death and hospitalization. Logistic regression was used to identify baseline characteristics associated with being bothered by lack of appetite. RESULTS: The risk of death was more than 2-fold higher [relative risk (RR) = 2.23; 95% confidence interval (CI) = 1.90-2.62] and the risk of hospitalization 33% higher (RR = 1.33; 95% CI = 1.19-1.48) among patients extremely bothered, compared with not bothered, by lack of appetite. These associations followed a dose-response fashion and remained statistically significant after adjustments for 14 comorbidities. Depression, shorter haemodialysis session, hypoalbuminaemia, lower concentration of serum creatinine and normalized protein catabolic rate, lower body mass index and higher leucocyte and neutrophil counts were independently associated with higher odds of being bothered by lack of appetite. CONCLUSIONS: The data suggest that a single question about lack of appetite helps identify haemodialysis patients with poorer nutritional status, inflammation, depression and higher risks of hospitalization and death. The study calls attention to a possible beneficial effect of longer haemodialysis on appetite.

Screening for depression in hemodialysis patients: associations with diagnosis, treatment, and outcomes in the DOPPS.

BACKGROUND: Depressive symptoms and depression are the most frequent psychologic problems reported by hemodialysis patients. We assessed the prevalence of depressive symptoms and physician-diagnosed depression, their variations by country, and associations with treatment by antidepressants among hemodialysis patients. We also assessed whether depressive symptoms were independently associated with mortality, hospitalization, and dialysis withdrawal. METHODS: The sample was represented by 9382 hemodialysis patients randomly selected from dialysis centers of 12 countries enrolled in the Dialysis Outcomes and Practice Patterns Study (DOPPS II). Depressive symptoms were assessed by the short version of the Center for Epidemiological Studies Depression Screening Index (CES-D), using > or =10 CES-D score as the cut-off value. RESULTS: Overall prevalence of physician-diagnosed depression was 13.9%, and percentage of CES-D score > or =10 43.0%. While the smallest prevalence of physician-diagnosed depression was observed in Japan (2.0%) and France (10.6%), the percentage of CES-D score > or =10 in these counties was similar to the whole sample. Patients on antidepressants also varied by country, 34.9% and 17.3% among those with physician-diagnosed depression and CES-D scores > or =10, respectively. In Cox models adjusted for several comorbidities, CES-D scores > or =10 were associated with significantly higher relative risks (RR) of death (RR = 1.42; 95% CI = 1.29 to 1.57), hospitalization (RR = 1.12; 95% CI = 1.03 to 1.22), and dialysis withdrawal (RR = 1.55; 95% CI = 1.29 to 1.85). CONCLUSION: The data suggest that depression is underdiagnosed and undertreated among hemodialysis patients. CES-D can help identify hemodialysis patients who are at higher risk of death and hospitalization. Interventions should target these patients with the goal to improve survival and reduce hospitalizations.