Dysnatremia and risk of bloodstream infection in dialysis patients.

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

The Interplay between Dietary Phosphorous, Protein Intake, and Mortality in a Prospective Hemodialysis Cohort.

(1) Background: Current dietary recommendations for dialysis patients suggest that high phosphorus diets may be associated with adverse outcomes such as hyperphosphatemia and death. However, there has been concern that excess dietary phosphorus restriction may occur at the expense of adequate dietary protein intake in this population. We hypothesized that higher dietary phosphorus intake is associated with higher mortality risk among a diverse cohort of hemodialysis patients. (2) Methods: Among 415 patients from the multi-center prospective Malnutrition, Diet, and Racial Disparities in Kidney Disease Study, we examined the associations of absolute dietary phosphorus intake (mg/day), ascertained by food frequency questionnaires, with all-cause mortality using multivariable Cox models. In the secondary analyses, we also examined the relationship between dietary phosphorus scaled to 1000 kcal of energy intake (mg/kcal) and dietary phosphorus-to-protein ratio (mg/g) with survival. (3) Results: In expanded case-mix + laboratory + nutrition adjusted analyses, the lowest tertile of dietary phosphorus intake was associated with higher mortality risk (ref: highest tertile): adjusted HR (aHR) (95% CI) 3.33 (1.75-6.33). In the analyses of dietary phosphorus scaled to 1000 kcal of energy intake, the lowest tertile of intake was associated with higher mortality risk compared to the highest tertile: aHR (95% CI) 1.74 (1.08, 2.80). Similarly, in analyses examining the association between dietary phosphorus-to-protein ratio, the lowest tertile of intake was associated with higher mortality risk compared to the highest tertile: aHR (95% CI) 1.67 (1.02-2.74). (4) Conclusions: A lower intake of dietary phosphorus was associated with higher mortality risk in a prospective hemodialysis cohort. Further studies are needed to clarify the relationship between specific sources of dietary phosphorus intake and mortality in this population.

Serum Thyrotropin Elevation and Coronary Artery Calcification in Hemodialysis Patients.

INTRODUCTION: Hypothyroidism is highly prevalent in end-stage kidney disease patients, and emerging data show that lower circulating thyroid hormone levels lead to downregulation of vascular calcification inhibitors and coronary artery calcification (CAC) in this population. To date, no studies have examined the association of serum thyrotropin (TSH), the most sensitive and specific single biochemical metric of thyroid function, with CAC risk in hemodialysis patients. METHODS: In secondary analyses of patients from the Anti-Inflammatory and Anti-Oxidative Nutrition in Hypoalbuminemic Dialysis Patients trial, we examined serum TSH levels and CAC risk assessed by cardiac computed tomography scans collected within a 90-day period. We evaluated the relationship between serum TSH with CAC Volume (VS) and Agatston score (AS) (defined as >100 mm3 and >100 Houndsfield Units, respectively) using multivariable logistic regression. RESULTS: Among 104 patients who met eligibility criteria, higher TSH levels in the highest tertile were associated with moderately elevated CAC VS and AS in case-mix-adjusted analyses (ref: lowest tertile): adjusted ORs (95% CIs) 4.26 (1.18, 15.40) and 5.53 (1.44, 21.30), respectively. TSH levels >3.0 mIU/L (ref: ≤3.0 mIU/L) were also associated with moderately elevated CAC VS and AS. In secondary analyses, point estimates of incrementally lower direct free thyroxine levels trended toward elevated CAC VS and AS, although associations did not achieve statistical significance. CONCLUSIONS: In hemodialysis patients, higher serum TSH was associated with elevated CAC VS and AS. Further studies are needed to determine if thyroid hormone supplementation can attenuate CAC burden in this population.

Dialysis symptom index burden and symptom clusters in a prospective cohort of dialysis patients.

BACKGROUND: Dialysis patients experience a high symptom burden, which may adversely impact their quality of life. Whereas other specialties emphasize routine symptom assessment, symptom burden is not well-characterized in dialysis patients. We sought to examine the prevalence and severity of unpleasant symptoms in a prospective hemodialysis cohort. METHODS: Among 122 hemodialysis patients from the prospective Malnutrition, Diet, and Racial Disparities in Chronic Kidney Disease (CKD) study, CKD-associated symptoms were ascertained by the Dialysis Symptom Index, a validated survey assessing symptom burden/severity (with higher scores indicating greater symptom severity), over 6/2020-10/2020. We examined the presence of (1) individual symptoms and symptom severity scores, and (2) symptom clusters (defined as ≥ 2 related concurrent symptoms), as well as correlations with clinical characteristics. RESULTS: Symptom severity scores were higher among non-Hispanic White and Hispanic patients, whereas scores were lower in Black and Asian/Pacific Islander patients. In the overall cohort, the most common individual symptoms included feeling tired/lack of energy (71.3%), dry skin (61.5%), trouble falling asleep (44.3%), muscle cramps (42.6%), and itching (42.6%), with similar patterns observed across racial/ethnic groups. The most prevalent symptom clusters included feeling tired/lack of energy + trouble falling asleep (37.7%); trouble falling asleep + trouble staying asleep (34.4%); and feeling tired/lack of energy + trouble staying asleep (32.0%). Lower hemoglobin, iron stores, and dialysis adequacy correlated with higher individual and overall symptom severity scores. CONCLUSION: We observed a high prevalence of unpleasant symptoms and symptom clusters in a diverse hemodialysis cohort. Further studies are needed to identify targeted therapies that ameliorate symptom burden in CKD.

Elevated serum thyrotropin levels and endothelial dysfunction in a prospective hemodialysis cohort.

INTRODUCTION: Thyroid dysfunction is a highly prevalent yet under-recognized complication in hemodialysis patients. In the general population, hypothyroidism has been associated with endothelial dysfunction due to impaired vasodilator synthesis and activity. Little is known about the association of serum thyrotropin (TSH), the most sensitive and specific single biochemical metric of thyroid function, with endothelial function in hemodialysis patients. METHODS: In a secondary analysis of 99 patients from the Anti-inflammatory and anti-oxidative nutrition in hypoalbuminemic dialysis patients (AIONID) trial, we examined measurements of serum TSH and endothelial function ascertained by fingertip digital thermal monitoring (DTM), a novel method used to measure micro-vascular reactivity, collected within a 90-day period. DTM was used to measure changes in fingertip temperature during and after an ischemic stimulus (blood pressure cuff occlusion) as an indicator of changes in blood flow, and two DTM indices were assessed, namely adjusted (a) Temperature Rebound (TR), defined as the maximum temperature rebound post-cuff deflation, and adjusted (b) Area Under the Temperature Curve (TMP-AUC), defined as area under the curve between the maximum and minimum temperatures. We examined the relationship between serum TSH with impaired TR (separately) and TMP-AUC (both defined as less than the median level of observed values) using multivariable logistic regression. FINDINGS: In unadjusted and case-mix analyses, higher serum TSH levels (defined as the three highest quartiles) were associated with lower (worse) TR (ref: lowest TSH quartile): ORs (95% CI) 2.64 (1.01-6.88) and 2.85 (1.08-7.57), respectively. In unadjusted and case-mix analyses, higher TSH levels were associated with lower (worse) TMP-AUC: ORs (95% CI) 2.64 (1.01-6.88) and 2.79 (1.06-7.38), respectively. DISCUSSION: In HD patients, higher serum TSH levels were associated with worse micro-vascular reactivity measured by DTM. Further studies are needed to determine if thyroid hormone supplementation improves endothelial function in hemodialysis patients with lower levels of thyroid function.

Dietary protein intake, kidney function, and survival in a nationally representative cohort.

BACKGROUND: High-protein diets (e.g., Paleo, Atkins, South Beach, ketogenic) have gained popularity as a means to promote weight loss and avoid excess carbohydrate consumption. Yet in chronic kidney disease (CKD) patients, evidence suggests low dietary protein intake (DPI) leads to attenuation of kidney function decline, although concerns remain for risk of protein-energy wasting. OBJECTIVES: To examine associations of DPI with mortality in a nationally representative cohort of US adults, stratified by kidney function. METHODS: We examined the association between daily DPI scaled to actual body weight (ABW), ascertained by 24-h dietary recall, with all-cause mortality among 27,604 continuous NHANES adult participants (1999-2010), stratified according to impaired versus normal kidney function (estimated glomerular filtration rates <60 compared with ≥60 ml/min/1.72 m2, respectively), using multivariable Cox models. We also examined the relation between high biological value (HBV) protein consumption with mortality. RESULTS: In participants with impaired kidney function, a high DPI of ≥1.4 g/kg ABW/day was associated with higher mortality, while lower DPI levels were not associated with mortality (reference, 0.6 to <1.0 g/kg ABW/day): the adjusted HRs (aHRs) were 1.09 (95% CI: 0.90, 1.32), 1.03 (95% CI: 0.82, 1.29), and 1.37 (95% CI: 1.02, 1.85) for DPI <0.6, 1.0 to <1.4, and ≥1.4 g/kg ABW/day, respectively. Yet in participants with normal kidney function, a low DPI of <0.6 g/kg ABW/day was associated with higher mortality, whereas higher DPI levels were not associated with death: the aHRs were 1.18 (95% CI: 1.04, 1.34), 0.92 (95% CI: 0.81, 1.04), and 0.99 (95% CI: 0.85, 1.16) for DPI <0.6, 1.0 to <1.4, and ≥1.4 g/kg ABW/day, respectively. The highest 2 tertiles of HBV consumption were associated with higher mortality in participants with impaired kidney function. CONCLUSIONS: Among participants with impaired kidney function, a higher DPI and greater HBV consumption were associated with higher mortality, whereas a lower DPI was associated with higher mortality in those with normal kidney function. Further studies are needed to elucidate the specific pathways between higher DPI and mortality in CKD.

Dietary Potassium Intake and Mortality in a Prospective Hemodialysis Cohort.

OBJECTIVES: Among hemodialysis patients, clinical practice guidelines recommend dietary potassium restriction given concerns about potential hyperkalemia leading to malignant arrhythmias and mortality. However, there are sparse data informing recommendations for dietary potassium intake in this population. We thus sought to examine the relationship between dietary potassium intake and death risk in a prospective cohort of hemodialysis patients. DESIGN AND METHODS: Among 415 hemodialysis patients from the prospective "Malnutrition, Diet, and Racial Disparities in Chronic Kidney Disease" cohort recruited across 16 outpatient dialysis clinics, information regarding dietary potassium intake was obtained using Food Frequency Questionnaires administered over October 2011 to March 2015. We first examined associations of baseline dietary potassium intake categorized as tertiles with mortality risk using Cox regression. We then examined clinical characteristics associated with low dietary potassium intake (defined as the lowest tertile) using logistic regression. RESULTS: In expanded case-mix Cox analyses, patients whose dietary potassium intake was in the lowest tertile had higher mortality (ref: highest tertile) (adjusted hazard ratio 1.74, 95% confidence interval 1.14-2.66). These associations had even greater magnitude of risk following adjustment for laboratory and nutritional covariates (adjusted hazard ratio 2.65, 95% confidence interval 1.40-5.04). In expanded case-mix restricted cubic spline analyses, there was a monotonic increase in mortality risk with incrementally lower dietary potassium intake. In expanded case-mix logistic regression models, female sex; higher serum bicarbonate; and lower dietary energy, protein, and fiber intake were associated with low dietary potassium intake. CONCLUSIONS: In a prospective cohort of hemodialysis patients, lower dietary potassium intake was associated with higher mortality risk. These findings suggest that excessive dietary potassium restriction may be deleterious in hemodialysis patients, and further studies are needed to determine the optimal dietary potassium intake in this population.

Residual Urine Output and Mortality in a Prospective Hemodialysis Cohort.

INTRODUCTION: Although residual urine output (UOP) is associated with better survival and quality of life in dialysis patients, frequent measurement by 24-hour urine collection is burdensome. We thus sought to examine the association of patients' self-reported residual UOP, as an alternative proxy of measured residual UOP, with mortality risk in a prospective hemodialysis cohort study. METHODS: Among 670 hemodialysis patients from the prospective multicenter Malnutrition, Diet, and Racial Disparities in Kidney Disease study, we examined associations of residual UOP, ascertained by patient self-report, with all-cause mortality. Patients underwent protocolized surveys assessing presence and frequency of UOP (absent, every 1-3 days, >1 time per day) every 6 months from 2011 to 2015. We examined associations of baseline and time-varying UOP with mortality using Cox regression. RESULTS: In analyses of baseline UOP, absence of UOP was associated with higher mortality in expanded case-mix adjusted Cox models (ref: presence of UOP): hazard ratio (HR), 1.78 (95% confidence interval [CI], 1.16-2.72). In analyses examining baseline frequency of UOP, point estimates suggested a graded association between lower frequency of UOP and higher mortality, although estimates for UOP every 1 to 3 days did not reach statistical significance (reference: UOP >1 time per day): HR, 1.29 (95% CI, 0.82-2.05) and HR, 1.97 (95% CI, 1.24-3.12) for UOP every 1 to 3 days and absence of UOP, respectively. Similar findings were observed in analyses of time-varying UOP. CONCLUSION: In hemodialysis patients, there is a graded association between lower frequency of self-reported UOP and higher mortality. Further studies are needed to determine the clinical impact of more frequent assessment of residual UOP using self-reported methods.

The Impact of Race and Ethnicity Upon Health-Related Quality of Life and Mortality in Dialysis Patients.

RATIONALE & OBJECTIVE: Health-related quality of life (HRQoL) has been recognized as a strong predictor of mortality among hemodialysis patients. However, differences in the association of HRQoL with survival across diverse racial/ethnic groups have not been well studied in this population. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: We examined the relationship between HRQoL and mortality in a prospective cohort of racially/ethnically diverse hemodialysis patients recruited from 18 outpatient dialysis units during 2011 to 2016. EXPOSURE: Using the 36-Item Short Form Health Survey (SF-36) administered every 6 months, HRQoL was ascertained by 36 questions summarized as 2 Physical and Mental Component and 8 subscale scores. OUTCOME: All-cause mortality. ANALYTICAL APPROACH: Associations of time-varying SF-36 scores with mortality were estimated using Cox models in the overall cohort and within racial/ethnic subgroups. RESULTS: Among 753 hemodialysis patients who met eligibility criteria, expanded case-mix analyses showed that the lowest quartiles of time-varying Physical and Mental Component scores were associated with higher mortality in the overall cohort (reference: highest quartile): adjusted HRs, 2.30 (95% CI, 1.53-3.47) and 1.54 (95% CI, 1.05-2.25), respectively. In analyses stratified by race/ethnicity, the lowest quartile of Physical Component scores was significantly associated with higher mortality across all groups: adjusted HRs, 2.64 (95% CI, 1.31-5.29), 1.84 (95% CI, 1.01-3.38), and 3.18 (95% CI, 1.13-8.91) for Hispanic, African American, and other race/ethnicity patients, respectively. The lowest quartile of time-varying physical functioning, role limitations due to physical health, role limitations due to emotional problems, social functioning, and pain subscale scores were associated with higher mortality in the overall cohort and particularly in Hispanics and blacks. LIMITATIONS: Residual confounding cannot be excluded. CONCLUSIONS: Lower SF-36 Physical Component and subscale scores were associated with higher mortality in hemodialysis patients, including those of minority background. Further studies are needed to determine whether interventions that augment physical health might improve the survival of these diverse populations.

Dialysate Potassium and Mortality in a Prospective Hemodialysis Cohort.

BACKGROUND: Studies examining the association of dialysate potassium concentration and mortality in hemodialysis patients show conflicting findings. We hypothesized that low dialysate potassium concentrations are associated with higher mortality, particularly in patients with high pre-dialysis serum potassium concentrations. METHODS: We evaluated 624 hemodialysis patients from the prospective Malnutrition, Diet, and Racial Disparities in Kidney Disease study recruited from 16 outpatient dialysis facilities over 2011-2015 who underwent protocolized collection of dialysis treatment characteristics every 6 months. We examined the association of dialysate potassium concentration, categorized as 1, 2, and 3 mEq/L, with all-cause mortality risk in the -overall cohort, and stratified by pre-dialysis serum potassium (< 5 vs. ≥5 mEq/L) using case-mix adjusted Cox models. RESULTS: In baseline analyses, dialysate potassium concentrations of 1 mEq/L were associated with higher mortality, whereas concentrations of 3 mEq/L were associated with similar mortality in the overall cohort (reference: 2 mEq/L): adjusted hazard ratios (aHRs; 95% CI) 1.70 (1.01-2.88) and 0.95 (0.64-1.39), respectively. In analyses stratified by serum potassium, baseline dialysate potassium concentrations of 1 mEq/L were associated with higher mortality in patients with serum potassium ≥5 mEq/L but not in those with serum potassium < 5 mEq/L: aHRs (95% CI) 2.87 (1.51-5.46) and 0.74 (0.27-2.07), respectively (p interaction = 0.04). These findings were robust with incremental adjustment for serum potassium, potassium-binding resins, and potassium-modifying medications. CONCLUSION: Low (1 mEq/L) dialysate potassium -concentrations were associated with higher mortality, particularly in hemodialysis patients with high pre-dialysis serum potassium. Further studies are needed to identify therapeutic strategies that mitigate inter-dialytic serum potassium accumulation and subsequent high dialysate serum potassium gradients in this population.

Dialysis Provider and Outcomes among United States Veterans Who Transition to Dialysis.

BACKGROUND AND OBJECTIVES: Veterans with ESKD initiate dialysis under the Veterans Health Administration (VHA), an integrated health system, or are outsourced to non-VHA providers. It is unknown whether outcomes differ according to their dialysis provider at initiation. We sought to evaluate the association between dialysis provider and mortality and hospitalization among United States veterans initiating dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 68,727 United States veterans who initiated dialysis in 2007-2014, we examined the association of dialysis provider (VHA versus non-VHA) at initiation with mortality and hospitalization rates in the first 12 months post-initiation. Associations were examined across adjusted models, accounting for demographics and comorbidities. RESULTS: Patients were 72±11 years, 5% were women, 24% were black, and 10% (n=7584) initiated at VHA dialysis centers. VHA dialysis center patients were younger, more likely to be black, had fewer cardiovascular comorbidities, and lower eGFR at dialysis initiation. VHA provider patients were more likely to be hospitalized in the first 12 months (adjusted incidence rate ratio, 1.10; 95% confidence interval, 1.07 to 1.14), but had lower all-cause mortality risk (adjusted hazard ratio, 0.87; 95% confidence interval, 0.83 to 0.93) in fully adjusted models. CONCLUSIONS: Veteran patients initiating dialysis with a VHA dialysis provider appear to have a lower mortality risk but higher hospitalization rates than veterans initiating dialysis at non-VHA dialysis units.

Association of Growth Differentiation Factor 15 with Mortality in a Prospective Hemodialysis Cohort.

BACKGROUND/AIMS: Cardiovascular disease and protein-energy wasting are among the strongest predictors of the high mortality of dialysis patients. In the general population, the novel cardiovascular and wasting biomarker, growth differentiation factor 15 (GDF15), is associated with decreased survival. However, little is known about GDF15 in dialysis patients. METHODS: Among prevalent hemodialysis patients participating in a prospective study (October 2011 to August 2015), we examined the association of baseline GDF15 levels with all-cause mortality using unadjusted and case mix-adjusted death hazard ratios (HRs) that controlled for age, sex, race, ethnicity, diabetes, and dialysis vintage. RESULTS: The mean age ± SD of the 203 patients included in the study was 53.2 ± 14.5 years, and the cohort included 41% females, 34% African-Americans, and 48% Hispanics. GDF15 levels (mean ± SD 5.94 ± 3.90 ng/mL; range 1.58-39.8 ng/mL) were higher among older patients and were inversely associated with serum creatinine concentrations as a surrogate for muscle mass. Each 1.0 ng/mL increase in GDF15 was associated with an approximately 17-18% higher mortality risk in the unadjusted and case mix models (p < 0.05). Increments of about 1 SD (a 4.0 ng/mL increase in GDF15) were associated with a nearly 2-fold higher death risk. The highest GDF15 tertile was associated with higher mortality risk (reference: lowest tertile): the HRs (95% CI) were 3.19 (1.35-7.55) and 2.45 (1.00-6.00) in the unadjusted and the case mix-adjusted model, respectively. These incremental death trends were confirmed in cubic spline models. CONCLUSION: Higher circulating GDF15 levels are associated with higher mortality risk in hemodialysis patients. Future studies are needed to determine whether GDF15 may represent a novel therapeutic target for cardiovascular disease, wasting, and death in this population.

Thyroid Status and Mortality in a Prospective Hemodialysis Cohort.

Context and Objective: Compared with the general population, hemodialysis patients have a substantially higher risk of hypothyroidism, as defined by an elevated serum thyrotropin (TSH) level, and cardiovascular mortality. Whereas an elevated TSH is associated with cardiovascular disease and death in the general population, associations among dialysis patients have been inconsistent. Design, Setting, Participants, and Main Outcome: We examined 541 hemodialysis patients from 17 southern California dialysis centers in the prospective Hypothyroidism, Cardiovascular Health, and Survival study who underwent protocolized measurement of repeated serum TSH levels every 6 months from 2013 to 2015. Associations between TSH tertiles (<1.28, 1.28 to <2.14, and 2.14 to 86.7 mIU/L) and mortality were estimated using time-dependent Cox models with four adjustment levels. In sensitivity analyses, we excluded patients receiving thyroid hormone supplementation. Results: Compared with the lowest TSH tertile, the highest TSH tertile was associated with a 2.2- to 2.5-fold higher mortality risk in unadjusted, case-mix, expanded case-mix+laboratory, and expanded case-mix+laboratory+medication models [hazard ratios (95% confidence interval), 2.54 (1.32 to 4.89), 2.53 (1.30 to 4.93), 2.19 (1.11 to 4.32), and 2.28 (1.45 to 3.58), respectively]. We observed a consistent trend between higher TSH tertiles and numerically higher mortality risk across all models. Similar findings were observed in analyses excluding patients receiving thyroid hormone supplementation. Conclusion: In time-dependent analyses, TSH levels in the high-normal to high range were independently associated with higher death risk in hemodialysis patients. Further studies are indicated to determine whether normalization of TSH levels with thyroid hormone supplementation improves survival in this population.

Association of Adiponectin With Body Composition and Mortality in Hemodialysis Patients.

BACKGROUND: In the general population, circulating adiponectin is associated with a favorable cardiovascular risk profile (eg, lower triglycerides and body fat) and decreased mortality. Hemodialysis (HD) patients have comparatively higher adiponectin concentrations, but prior studies examining the adiponectin-mortality association in this population have not accounted for body composition or shown a consistent relationship. STUDY DESIGN: Prospective cohort study. SETTINGS & PARTICIPANTS: We examined baseline serum adiponectin concentrations in 501 HD patients across 13 dialysis centers from the prospective MADRAD (Malnutrition, Diet, and Racial Disparities in Chronic Kidney Disease) cohort (entry period, October 2011 to February 2013; follow-up through August 2013). PREDICTOR: Serum adiponectin concentration in tertiles (tertiles 1, 2, and 3 defined as ≤16.1, >16.1-<30.1, and ≥30.1-100.0 µg/mL, respectively). Adjustment variables included case-mix and laboratory test results (age, sex, race, ethnicity, vintage, diabetes, serum albumin, total iron-binding capacity, serum creatinine, white blood cell count, phosphate, hemoglobin, and normalized protein catabolic rate), body composition surrogates (subcutaneous, visceral, and total-body fat and lean body mass), and serum lipid levels (cholesterol, high-density lipoprotein cholesterol, and triglycerides). OUTCOMES: All-cause mortality using survival (Cox) models incrementally adjusted for case-mix and laboratory test results. RESULTS: Among 501 HD patients, 50 deaths were observed during 631.1 person-years of follow-up. In case-mix- and laboratory-adjusted Cox analyses, the highest adiponectin tertile was associated with increased mortality versus the lowest tertile (HR, 3.35; 95% CI, 1.50-7.47). These associations were robust in analyses that additionally accounted for body composition (HR, 3.18; 95% CI, 1.61-8.24) and lipid levels (HR, 3.64; 95% CI, 1.34-7.58). LIMITATIONS: Residual confounding cannot be excluded. CONCLUSIONS: Higher adiponectin level is associated with a 3-fold higher death risk in HD patients independent of body composition and lipid levels. Future studies are needed to elucidate underlying mechanisms and determine therapeutic targets associated with improved outcomes in HD patients.