Hemodialysis Study Research Articles

Correction: Interaction of healthcare staff's attitude with barriers to physical activity in hemodialysis patients: A quantitative assessment.

[This corrects the article DOI: 10.1371/journal.pone.0196313.].

Associations of Dietary Protein and Energy Intakes With Protein-Energy Wasting Syndrome in Hemodialysis Patients

IntroductionThe associations of dietary protein and/or energy intakes with protein or energy wasting in patients on maintenance hemodialysis are controversial. We examined these in the Hemodialysis (HEMO) Study.MethodsIn 1487 participants in the HEMO Study, baseline dietary protein intake (grams per kilogram per day) and dietary energy intake (kilocalories per kilograms per day) were related to the presence of the protein-energy wasting (PEW) syndrome at month 12 (defined as the presence of at least 1 criteria in 2 of the 3 categories of low serum chemistry, low body mass, and low muscle mass) in logistic regression models. In additional separate models, protein intake estimated from equilibrated normalized protein catabolic rate (enPCR) was also related to the PEW syndrome.ResultsCompared with the lowest quartile, the highest quartile of baseline dietary protein intake was paradoxically associated with increased risk of the PEW syndrome at month 12 (odds ratio [OR]: 4.11; 95% confidence interval [CI]: 2.79–6.05). This relationship was completely attenuated (OR: 1.35; 95% CI: 0.88–2.06) with adjustment for baseline body weight, which suggested mathematical coupling. Results were similar for dietary energy intake. Compared with the lowest quartile of baseline enPCR, the highest quartile was not associated with the PEW syndrome at 12 months (OR: 0.78; 95% CI: 0.54–1.12).DiscussionThese data do not support the use of dietary protein intake or dietary energy intake criteria in the definition of the PEW syndrome in patients on maintenance hemodialysis.

A two-pool kinetic model predicts phosphate concentrations during and shortly following a conventional (three times weekly) hemodialysis session.

Previous studies have suggested that a conventional two-pool model cannot be used to predict intradialysis and early postdialysis phosphorus concentrations. A conventional two-pool urea model was modified by increasing the distal compartment volume from two-thirds to three times the total body water and by the use of a dynamically variable intercompartmental phosphorus clearance during dialysis. The phosphate solver model parameters were derived from an examination of the results in the literature, and fine-tuned using a training set (F4) of 415 Hemodialysis (HEMO) Study patients studied during a dialysis session where phosphorus was measured at 4 months of follow-up. Validation was done in a group of 380 different HEMO Study patients plus 9 from the original F4 group, who were evaluated at 36 months of follow-up. The model predicted measured median early (1 h) intradialysis, end-dialysis and 30-min postdialysis serum phosphorus levels in the test and validation datasets with little apparent bias, including the highest and lowest deciles of predialysis serum phosphorus. The model tended to underestimate slightly intradialysis serum phosphorus when predialysis serum phosphorus was <3.0 mg/dL (0.97 mmol/L). There was a large scatter and standard deviation among patients, and whether aberrant values represent a patient-specific phenomenon is unclear. A modified two-pool model using a slightly expanded distal compartment and a dynamically varying intercompartmental clearance, depending on the intradialysis phosphorus concentration, can be used to predict serum phosphorus level during and shortly after dialysis, in patients following a conventional three times per week dialysis prescription.

Kt/Vurea and Nonurea Small Solute Levels in the Hemodialysis Study.

The Hemodialysis (HEMO) Study showed that high-dose hemodialysis providing a single-pool Kt/Vurea of 1.71 provided no benefit over a standard treatment providing a single-pool Kt/Vurea of 1.32. Here, we assessed whether the high-dose treatment used lowered plasma levels of small uremic solutes other than urea. Measurements made ≥3 months after randomization in 1281 patients in the HEMO Study showed a range in the effect of high-dose treatment compared with that of standard treatment: from no reduction in the level of p-cresol sulfate or asymmetric dimethylarginine to significant reductions in the levels of trimethylamine oxide (-9%; 95% confidence interval [95% CI], -2% to -15%), indoxyl sulfate (-11%; 95% CI, -6% to -15%), and methylguanidine (-22%; 95% CI, -18% to -27%). Levels of three other small solutes also decreased slightly; the level of urea decreased 9%. All-cause mortality did not significantly relate to the level of any of the solutes measured. Modeling indicated that the intermittency of treatment along with the presence of nondialytic clearance and/or increased solute production accounted for the limited reduction in solute levels with the higher Kt/Vurea In conclusion, failure to achieve greater reductions in solute levels may explain the failure of high Kt/Vurea treatment to improve outcomes in the HEMO Study. Furthermore, levels of the nonurea solutes varied widely among patients in the HEMO Study, and achieved Kt/Vurea accounted for very little of this variation. These results further suggest that an index only on the basis of urea does not provide a sufficient measure of dialysis adequacy.

Hemodialysis: Core Curriculum 2014

From the Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN. Received May 1, 2013. Accepted in revised form July 1, 2013. Originally published online November 21, 2013. Address correspondence to Thomas A. Golper, MD, S3303 Medical Center North, Vanderbilt University Medical Center, 21st Ave S, Nashville, TN 37232. E-mail: thomas.golper@vanderbilt. edu 2013 by the National Kidney Foundation, Inc. 0272-6386/$36.00 http://dx.doi.org/10.1053/j.ajkd.2013.07.028 PRINCIPLES OF DIALYSIS AND HOW MODALITIES DIFFER

Changes in Anthropometry and Mortality in Maintenance Hemodialysis Patients in the HEMO Study

Poor nutritional status has been associated with worse patient survival in maintenance hemodialysis patients. Anthropometric values are important nutritional measures, incorporating muscle and fat mass. However, the association of changes in anthropometry, including midarm circumference (MAC) and skinfold measurements, with mortality in hemodialysis patients remains unknown. Accordingly, we explored this association in the Hemodialysis (HEMO) Study. Post hoc analysis of cohort data from a clinical trial. 1,846 hemodialysis patients enrolled in the HEMO Study. MAC and skinfold measurements. Longitudinal changes in MAC and skinfolds were jointly modeled using repeated measures and survival modeling. Time-to-event outcomes were all-cause mortality, cardiac death and hospitalization, and infection-related death. Mean MAC was 30.1 cm, and mean baseline sum of subscapular, biceps, and triceps skinfolds was 42.4 mm. During a median follow-up of 2.5 years, there were 845 deaths. During follow-up, MAC and the skinfold measurement declined 0.26 cm and 1.1 mm per year, respectively. Declines in MAC (per cm) and skinfold (per mm) measurements were associated with higher all-cause mortality (HRs of 1.58 [95% CI, 1.29-1.94; P < 0.001] and 1.06 [95% CI, 0.99-1.13; P = 0.09], respectively), poorer cardiac outcomes (HRs of 1.49 [95% CI, 1.23-1.81; P < 0.001] and 1.05 [95% CI, 0.99-1.10; P = 0.09], respectively), and higher infection-related hospitalization (HRs of 2.45 [95% CI, 1.55-3.88; P < 0.001] and 1.16 [95% CI, 0.98-1.37; P = 0.08], respectively). The association between declining MAC and skinfold with patient survival was most notable for those with body mass index (BMI) ≤25 kg/m2 (HRs of 2.41 [95% CI, 1.81-3.19; P < 0.001] and 1.22 [95% CI, 1.10-1.35; P < 0.001], respectively). Prevalent dialysis patients only, excluding individuals weighing >85 kg. Declines in skinfold thickness were not associated significantly with outcomes except for participants with BMI ≤25 kg/m2. Declines in MAC are associated significantly with all-cause mortality and cardiac outcomes in hemodialysis patients, most notably in those with BMI ≤25 kg/m2.

Joint Modeling of All-Cause Mortality and Longitudinally Measured Serum Albumin

In clinical studies, longitudinal and survival data are often obtained simultaneously from the same individual. Linear mixed effects models are widely used for analyzing longitudinal continuous outcome data, while survival models are used for analyzing time-to-event data. It is a common practice to analyze these longitudinal and time-to-event data separately. However, when multivariate outcomes are obtained from a given individual, they can be correlated by nature, and one can attain considerable gain in efficiency by jointly analyzing the outcomes. An objective of this study is to analyze such multivariate data by jointly modeling longitudinally measured continuous outcomes and time-to-event data. In this joint modeling, we formulate a joint likelihood function for both outcomes and use the maximum likelihood method to estimate the parameters in the two sub-models (longitudinal and survival models). We demonstrate the merits of joint modeling by considering a joint analysis of longitudinally measured serum albumin (biomarker) and time-to-all-cause mortality data obtained from a hemodialysis (HEMO) study. This HEMO study was a large NIH (National Institute of Health) sponsored multicenter clinical trial contrasting the effects of dialysis dose and dialysis membrane permeability in end-stage renal disease patients receiving hemodialysis. We find that the parameter estimates obtained under joint modeling of HEMO data are more efficient than those obtained under separate modeling of the outcome variables.

All-cause and cause-specific mortality associated with diabetes in prevalent hemodialysis patients

BackgroundDiabetes is the most common risk factor for end-stage renal disease (ESRD) and has been associated with increased risk of death. In order to better understand the influence of diabetes on outcomes in hemodialysis, we examine the risk of death of diabetic participants in the HEMODIALYSIS (HEMO) study.MethodsIn the HEMO study, 823 (44.6%) participants were classified as diabetic. Using the Schoenfeld residual test, we found that diabetes violated the proportional hazards assumption. Based on this result, we fit two non-proportional hazard models: Cox’s time varying covariate model (Cox-TVC) that allows the hazard for diabetes to change linearly with time and Gray’s time-varying coefficient model.ResultsUsing the Cox-TVC, the hazard ratio (HR) for diabetes increased with each year of follow up (p = 0.02) for all cause mortality. Using Gray’s model, the HR for diabetes ranged from 1.41 to 2.21 (p <0.01). The HR for diabetes using Gray’s model exhibited a different pattern, being relatively stable at 1.5 for the first 3 years in the study and increasing afterwards.ConclusionRisk of death associated with diabetes in ESRD increases over time and suggests that an increasing risk of death among diabetes may be underappreciated when using conventional survival models.

Peripheral vascular disease severity impacts health outcomes and health-related quality of life in maintenance hemodialysis patients in the HEMO Study

In patients with end-stage renal disease, peripheral vascular disease (PVD) is prevalent. We assessed the extent to which severity of PVD predicts mortality, hospitalizations and health-related quality of life (HRQOL) in hemodialysis (HD) patients enrolled in the Hemodialysis (HEMO) Study. We performed a subanalysis of the HEMO Study, a randomized controlled trial. Adjusted predictors of PVD were analyzed through a multivariable stepwise ordinal logistic model. Relationships between PVD severity and mortality and hospitalizations were determined with Cox proportional hazards models. Relationships between PVD severity and HRQOL were modeled via linear regression and generalized estimating equations. Older age, diabetes, non-African-American race, ischemic heart disease, cerebrovascular disease and longer transplant wait time were associated with more severe PVD. Patients with severe PVD were more likely to suffer from all-cause mortality [hazard ratio (HR) 1.77, 95% confidence interval 1.30-2.40, P<0.001], cardiac death [HR 1.89 (95% confidence interval 1.15-3.11), P=0.001] and infectious death [HR 1.75 (95% confidence interval 1.30-2.34), P<0.001]. Increasing PVD severity was also associated with first cardiac hospitalization or all-cause mortality (P=0.05) and first cardiac hospitalization or cardiac death (P=0.03). HRQOL scores were lower for patients with increasingly severe PVD. These findings underscore the burden of clinically symptomatic PVD in HD patients and its impact on morbidity and mortality. Whether early detection of PVD and prompt initiation of therapy to prevent its progression in the HD population would improve HRQOL and survival outcomes remain to be proven.

Uraemic toxins versus volume and water as the major factor that matters with dialysis

In this pro-con debate, we will analyse the relevance of data supporting the prime role of uraemic toxins versus salt and volume overload as the main driver for the impressive mortality and morbidity characteristic of any end-stage re- nal disease patient. Firstly, we are going to review the circumstantial evidence and associated studies/clinical observational data which only weakly suggest that uraemic solutes are indeed linked to damage to the body and its constituents, especially the car- diovascular (CV) system. At the same time, we will equally thoroughly discuss the 'fact' that decreasing salt and fluid load is essential for any dialysed patient. Evidence in favour of a prominent role for uraemic toxins is appealing from a pathophysiological point of view, but unfortunately is mis- leading in real life practice. Evidence in favour of salt and water reduction is overwhelmingly stronger. This difference in apparent evidence strength notwith- standing the weaker support for uraemic toxins does not take away from clinical importance of minimizing uraemic tox- icity load in the large majority of the dialysis population. filtration (HDF) or more frequent/longer dialysis, was only partially associated with better results. Moreover, in the ma- jority of the positive studies, alternative interpretations of the results is possible, including a contribution of better volume control achievable with these particular dialysis techniques. Some 'observational' studies (2-7) showed a beneficial effect of high-flux versus low-flux synthetic dialysis mem- branes on survival, whereas prospective random controlled trials (RCTs) were inconclusive. In the Haemodialysis (HEMO) study, the largest random- ized clinical trial conducted in haemodialysis (HD) so far, patients were randomized to either a high-dialysis dose (achieved eKt/V ¼ 1.53 � 0.09, sp Kt/V ¼ 1.71 � 0.11) or a standard-dose goal (achieved eKt/V ¼ 1.16 � 0.08, sp Kt/V ¼ 1.32 � 0.09) and to dialysis with either high-flux dialysers (b2-microglobulin clearance of > 20 mL/min) or to low-flux dialysers—(b2-microglobulin clearance < 10 mL/ min). The results showed that a higher HD dose was not associated with a lower mortality risk compared with con- ventional HD dose (8). Thus, while a minimumKt/V ,a ccord- ing to the guidelines, is mandatory, the HEMO study clearly demonstrated that there are no advantages in further increas- ing the urea Kt/V, even in the high-flux membrane group. At the same time, each 10 mg/L increase in b2-M level was associated with an 11% increase in mortality, even after ad- justment for years on dialysis and residual kidney function. These results deserve further specifically designed studies in order to clarify if it is a matter of larger molecule removal or better fluid removal. In the other large trial in the field, the Membrane Perme- ability Outcome study, there was no significant difference in survival between high- and low-flux groups when all patients were included in the analysis (9). However, patients with serum albumin � 40 g/L on enrolment and with diabetes had a significantly better survival in the high-flux arm. High-flux dialysis was associated with a significantly lower accumulation of b2-microglobulin. Again, it is important to clarify if the better outcome was related to larger molecule removal or better fluid removal. Compared with conventional HD, HDF could theoretically offer some advantages: better clearance of middle- and

Is Nutritional Status Associated With Self-reported Sleep Quality in the HEMO Study Cohort?

To explore the relationship between sleep quality and common measures of nutritional status in the Hemodialysis (HEMO) Study cohort. To investigate sleep quality scores based on longitudinal changes in measures of nutritional status, adjusting for case mix, lifestyle, and comorbidity factors. Secondary analysis of the HEMO Study data. A 7-year, prospective, multicenter, randomized clinical trial in maintenance hemodialysis patients. Eighteen hundred forty-six patients aged between 18 and 80 years were randomized; 1,803 (97.7%) completed the Kidney Disease Quality of Life Long Form (KDQOL-LF) at baseline. Mean age was 58 years, 44% were male, 64% were Black, 37% had diabetes, and 32% had hypertension; mean duration of dialysis was 3.8 years. The univariate and multivariate relationships of measures of nutritional status (i.e., serum albumin, serum creatinine, postdialysis weight, body mass index, dietary protein and energy intake, and assessment of appetite) and sleep quality assessed using the sleep subscale from the KDQOL-LF. In univariate analysis, sleep quality score decreased significantly in a linear fashion as appetite rating decreased from very good to very poor on both dialysis days (63.6 ± 21.8 to 43.6 ± 22.9, P < .0001) and nondialysis days (63.2 ± 21.6 to 40.7 ± 25.7, P < .0001), with higher scores reflecting better sleep quality. In multivariable analysis, serum creatinine was the only laboratory variable that was significantly associated with sleep quality score (β = 0.49, P = .0004). Poorer appetite on both dialysis days (β = -1.5, P < .0001) and nondialysis days (β = -1.7, P < .0001) was associated with poor sleep quality. Self-reported sleep quality was associated with appetite and serum creatinine. A simple questionnaire to assess sleep disorders in dialysis patients should be administered routinely to detect those patients at risk of sleep complaints. However, further studies are needed to determine whether improving sleep quality, directly or indirectly, would improve morbidity and mortality.

β-Blockers for Prevention of Sudden Cardiac Death in Patients on Hemodialysis: A Propensity Score Analysis of the HEMO Study

Hemodialysis patients have an elevated risk of sudden cardiac death. Although the efficacy of β-blockers for the prevention of sudden cardiac death has been proven in the general population, little evidence exists in patients with kidney failure. Post hoc analysis of the Hemodialysis (HEMO) Study. Participants enrolled in the HEMO Study from May 1995 to February 2001. β-Blocker use ascertained through self-reported questionnaires and dialysis clinic charts. Sudden cardiac death adjudicated by a committee as a secondary outcome of interest. We used Cox proportional hazards regression models, competing risk survival analysis, propensity score matching, and covariate adjustment to study the association of β-blockers with sudden cardiac death. 1,747 patients were included in this study, and 521 were on β-blocker therapy at baseline. Mean age was 58 years, 57% were women, and 39% had ischemic heart disease (IHD) at baseline. Baseline β-blocker use was not associated with lower risk of sudden cardiac death in univariate (cause-specific HR, 0.89; 95% CI, 0.64-1.24), multivariable (cause-specific HR, 0.87; 95% CI, 0.62-1.22), or propensity-matched (cause-specific HR, 0.91; 95% CI, 0.55-1.50) analyses. There was a significant interaction between β-blocker use and sudden cardiac death (interaction P = 0.03) in patients with (cause-specific HR, 0.65; 95% CI, 0.42-1.01) and without IHD (cause-specific HR, 1.61; 95% CI, 0.92-2.80). Observational nature of the study. In hemodialysis patients without preexisting IHD, β-blocker use was not associated with lower risk of sudden cardiac death. However, there was a trend toward benefit in those with IHD.

Impact of Fatigue on Outcomes in the Hemodialysis (HEMO) Study

Background: Fatigue is a common debilitating symptom in chronic kidney disease patients on maintenance hemodialysis. However, little is known about its pathogenesis and association with survival. Methods: This study examines the correlates and outcomes of fatigue among 1,798 hemodialysis patients enrolled in the HEMO study. Fatigue was assessed using the SF-36 vitality scale. Multivariable analysis was used to assess independent associations of demographic and clinical characteristics with baseline fatigue and longitudinal changes in fatigue. The association of fatigue with all-cause and cause-specific mortality and cardiac hospitalizations was also assessed. Results: Higher index of coexistent diseases (ICED) score, diabetes, non-African-American race, lower serum albumin, use of medications for sleep and poor sleep quality were found to be significantly associated with more fatigue at baseline. In longitudinal analyses, patients who were older, had been on dialysis longer, had higher ICED score, and reported using medications for sleep were more likely to experience worsening fatigue, whereas higher serum albumin was strongly associated with an improvement in level of fatigue. A 10-point increase in vitality score was associated with 10% increase in mean survival (p < 0.0001). Conclusions: Demographic and clinical factors have significant associations with fatigue, which itself predicts mortality. Improving fatigue in the end-stage renal disease population may positively impact patient well-being and survival.

Modeled Urea Distribution Volume and Mortality in the HEMO Study

In the Hemodialysis (HEMO) Study, observed small decreases in achieved equilibrated Kt/V(urea) were noncausally associated with markedly increased mortality. Here we examine the association of mortality with modeled volume (V(m)), the denominator of equilibrated Kt/V(urea). Parameters derived from modeled urea kinetics (including V(m)) and blood pressure (BP) were obtained monthly in 1846 patients. Case mix-adjusted time-dependent Cox regressions were used to relate the relative mortality hazard at each time point to V(m) and to the change in V(m) over the preceding 6 months. Mixed effects models were used to relate V(m) to changes in intradialytic systolic BP and to other factors at each follow-up visit. Mortality was associated with V(m) and change in V(m) over the preceding 6 months. The association between change in V(m) and mortality was independent of vascular access complications. In contrast, mortality was inversely associated with V calculated from anthropometric measurements (V(ant)). In case mix-adjusted analysis using V(m) as a time-dependent covariate, the association of mortality with V(m) strengthened after statistical adjustment for V(ant). After adjustment for V(ant), higher V(m) was associated with slightly smaller reductions in intradialytic systolic BP and with risk factors for mortality including recent hospitalization and reductions in serum albumin concentration and body weight. An increase in V(m) is a marker for illness and mortality risk in hemodialysis patients.

Rapid fluid removal during dialysis is associated with cardiovascular morbidity and mortality

Patients receiving hemodialysis have high rates of cardiovascular morbidity and mortality that may be related to the hemodynamic effects of rapid ultrafiltration. Here we tested whether higher dialytic ultrafiltration rates are associated with greater all-cause and cardiovascular mortality, and hospitalization for cardiovascular disease. We used data from the Hemodialysis Study, an almost-7-year randomized clinical trial of 1846 patients receiving thrice-weekly chronic dialysis. The ultrafiltration rates were divided into three categories: up to 10 ml/h/kg, 10-13 ml/h/kg, and over 13 ml/h/kg. Compared to ultrafiltration rates in the lowest group, rates in the highest were significantly associated with increased all-cause and cardiovascular-related mortality with adjusted hazard ratios of 1.59 and 1.71, respectively. Overall, ultrafiltration rates between 10-13 ml/h/kg were not associated with all-cause or cardiovascular mortality; however, they were significantly associated among participants with congestive heart failure. Cubic spline interpolation suggested that the risk of all-cause and cardiovascular mortality began to increase at ultrafiltration rates over 10 ml/h/kg regardless of the status of congestive heart failure. Hence, higher ultrafiltration rates in hemodialysis patients are associated with a greater risk of all-cause and cardiovascular death.

Effect of Membrane Permeability on Survival of Hemodialysis Patients

The biologic plausibility of clinical benefits of high-flux compared with low-flux hemodialysis is supported by observations that numerous molecules with known biologic activities and potentially harmful effects accumulate in the plasma of patients with ESRD and are preferentially cleared by high-flux dialysis. In addition to β2-microglobulin, which is often used as a plasma marker, examples of these toxic middle molecules include parathyroid hormones, advanced glycation products of various molecular weights,1 leptin,2 apolipoprotein C-III,3 and several molecules that inhibit granulocyte functions.4 Empirical support for the clinical benefits of high-flux dialysis is provided by observational studies that report associations of high-flux dialysis with reduced mortality5; however, the Hemodialysis (HEMO) Study, a randomized trial performed in 1846 hemodialysis patients in the United States between 1995 and 2001, failed to demonstrate a decrease in its primary end point of all-cause mortality (hazard ratio [HR] 0.92; 95% confidence interval [CI] 0.81 to 1.05) with high-flux compared with low-flux dialysis.6 Nonetheless, because the lower limit of the CI could not rule out an overall hazard reduction of up to 19% and because secondary analyses showed trends favoring high flux for all-cause mortality in patients with >3.7 yr of previous dialysis7 and for cardiac mortality in the full cohort,6,8 …

Disordered Mineral Metabolism in Hemodialysis Patients: An Analysis of Cumulative Effects in the Hemodialysis (HEMO) Study

Serum markers of disordered mineral metabolism have been associated with adverse outcomes in patients requiring long-term dialysis therapy. Although the values of these markers often evolve over time, no study has examined the accumulated effects of these abnormalities on important clinical end points. Retrospective cohort study. 1,846 prevalent hemodialysis patients randomly assigned in the Hemodialysis (HEMO) Study. Serum phosphorus, calcium, calcium-phosphorus (Ca x P) product, and intact parathyroid hormone, each analyzed at the time of randomization (baseline), as a standard time-dependent covariate and as a cumulative time-dependent covariate. All-cause mortality and the composite of all-cause mortality and first cardiac hospitalization. Cox proportional hazards models. In all analyses, serum phosphorus level greater than 6 mg/dL was associated with a heightened risk of mortality of approximately 25% compared with phosphorus values of 4.1 to 5 mg/dL. Serum calcium level greater than 11 mg/dL was associated with a 60% greater risk of death, but only when this parameter was analyzed as either a time-dependent or cumulative time-dependent variable. Ca x P product greater than 50 mg(2)/dL(2) was strongly associated with mortality, but only when assessed cumulatively. Similar relationships were observed when phosphorus, calcium, and Ca x P product values were related to the composite end point of all-cause mortality and first cardiac hospitalization. No relationships between baseline, time-dependent, and cumulative time-dependent intact parathyroid hormone levels and the outcomes of interest were observed. Residual confounding, lack of access to patient information before randomization in the HEMO Study, and concerns regarding generalizability given changes in practice patterns since the completion of the HEMO Study. Cumulative time-dependent analyses provide a different framework for analyzing the impact of factors that may mediate adverse events in hemodialysis patients. Our findings support maintaining serum phosphorus levels at less than 6 mg/dL, calcium levels at less than 11 mg/dL, and Ca x P product at less than 50 mg(2)/dL(2).

Plasma adiponectin levels and clinical outcomes among haemodialysis patients

Adiponectin (ADPN) levels are consistently elevated among patients with advanced chronic kidney disease, but its relationship with cardiovascular outcomes in this population remains controversial. We measured baseline and yearly plasma ADPN in 182 prevalent haemodialysis patients recruited to the Haemodialysis (HEMO) Study from two Boston centres. Plasma ADPN at baseline and during follow-up was studied in relation to prevalent cardiovascular disease (CVD) and cardiovascular and all-cause mortality. Baseline plasma ADPN levels were found to be approximately twofold higher than in the general population and correlated inversely with (log-transformed) CRP levels and (log-transformed) body mass index (BMI). Levels measured over time showed a gradual increase (0.95 microg/mL, 95% CI = 0.12-1.78 microg/mL; P = 0.03) by year, although this difference became non-significant after adjustment for covariates. Baseline ADPN levels were lower among patients with pre-existing CVD (adjusted OR of 0.67; P = 0.03). They also predicted all-cause mortality (P < 0.01) and the composite outcome of 'cardiovascular events/cardiovascular mortality' (P < 0.01); levels measured over time predicted the composite outcome of 'cardiovascular events and all-cause mortality' (P < 0.01). These relationships were non-linear (quadratic) with the hazard for each outcome increasing in the lower and upper ranges of the distribution of ADPN, and strengthened after adjustment for baseline covariates including serum albumin, CVD and the flux and dialysis dose categorization of the HEMO study. In summary, low plasma levels of ADPN were associated with inflammation and pre-existing CVD; ADPN levels predicted cardiovascular and mortality outcomes, the relationship being extensively confounded by multiple patient-related factors.

Inflammation and Inverse Associations of Body Mass Index and Serum Creatinine With Mortality in Hemodialysis Patients

Protein-energy wasting and inflammation are common and associated with an increased risk of mortality in hemodialysis (HD) patients. We examined the extent to which they mediate the associations of each other with death in this population. Retrospective analysis of the Hemodialysis (HEMO) Study data. Prevalent HD patients. One-thousand HEMO study participants with data available on C-reactive protein (CRP), body mass index (BMI), and serum creatinine. None. The associations of CRP, BMI, and serum creatinine with time to all-cause mortality separately and together in multivariate Cox models. In 1,437 patient-years of follow-up, there were 265 (26.5%) all-cause deaths. Compared with the lowest CRP quartile, the highest quartile was associated with a hazard ratio (HR) of 2.02 (95% confidence interval [CI], 1.31-3.10) for all-cause mortality. This association of highest CRP quartile with mortality was not attenuated with further adjustment for BMI and serum creatinine (HR, 2.13; 95% CI, 1.38-3.30). When serum albumin was added to the model, the hazard of death associated with highest CRP quartile was modestly attenuated (HR, 1.88; 95% CI, 1.21-2.92). In contrast, both BMI (for each kg/m2 increase; HR, 0.94; 95% CI, 0.91-0.96 for all-cause mortality) and serum creatinine (for each mg/dL increase; HR, 0.85; 95% CI, 0.79-0.90 for all-cause mortality) had strong, independent protective effects. Further adjustment with CRP had a negligible effect on these associations. The associations of markers of nutrition and inflammation with mortality are largely independent of each other in HD patients.

Cerebrovascular Disease in Maintenance Hemodialysis Patients: Results of the HEMO Study

Cerebrovascular disease (CBVD) in hemodialysis patients is associated with significant morbidity and mortality. A secondary analysis of CBVD in the Hemodialysis (HEMO) Study was performed. Specific objectives were to: (1) determine risk factors for the presence of CBVD at baseline, (2) assess risk factors for the subsequent occurrence of cerebrovascular deaths, and (3) analyze the effects of dose and flux on cerebrovascular mortality. The HEMO Study was a randomized multicenter study evaluating the effects of high-dose versus standard-dose and high-flux versus low-flux hemodialysis. There were 1,846 patients enrolled, with a mean follow-up of 2.84 years. Factors associated with the baseline presence of CBVD included age (P < 0.0001), presence of any cardiac disease (P < 0.0001), and diabetes mellitus (P < 0.0001). There were 65 deaths caused by CBVD (event rate, 1.2/100 patient-years). Multivariate Cox regression using a backward-variables selection procedure showed that diabetes, lower albumin level, greater hematocrit, and lower body mass index at baseline were associated significantly with subsequent CBVD death. There was no effect of flux or dose on overall rate of CBVD deaths. However, an interaction was found between baseline CBVD status and flux intervention on CBVD death (P = 0.016). In the subgroup of patients without the baseline presence of CBVD, high-flux dialysis was associated with a lower risk for death caused by CBVD (P = 0.016). A borderline interaction between years of dialysis therapy and flux on subsequent CBVD death was detected (P = 0.05). The beneficial effect of high flux was evident in those on hemodialysis therapy for longer than 3.7 years (P = 0.012). High flux was associated with decreased CBVD mortality in those without known CBVD at baseline and those on hemodialysis therapy for longer than 3.7 years. This secondary analysis strengthens, but does not prove, the hypothesis that high-flux treatment may attenuate the death rate from vascular disease.