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BackgroundThe inverse association between body mass index (BMI) and mortality observed in patients treated with maintenance hemodialysis (MHD), also known as the obesity paradox, may be a result of residual confounding. Marginal structural model (MSM) analysis, a technique that accounts for time-varying confounders, may be more appropriate to investigate this association. We hypothesize that after applying MSM, the inverse association between BMI and mortality in MHD patients is attenuated.MethodsWe examined the associations between BMI and all-cause mortality among 123 624 adult MHD patients treated during 2001-6. We examined baseline and time-varying BMI using Cox proportional hazards models and MSM while considering baseline and time-varying covariates, including demographics, comorbidities and markers of malnutrition and inflammation.ResultsThe patients included 45% women and 32% African Americans with a mean age of 61(SD 15) years. In all models, BMI showed a linear incremental inverse association with mortality. Compared with the reference (BMI 25 to

Aggressive NIH is a common histopathological lesion found at the sites of venous stenosis in arteriovenous fistula (AVF) and arteriovenous grafts (AVG). Inflammatory mediators have been proposed to play a pathogenic role in NIH, but there is paucity of data evaluating this hypothesis in clinical studies or in animal models. Serum levels of inflammatory mediators can potentially identify patients at high risk of AVF and AVG dysfunction. In a cross-sectional cohort study of 754 HD patients who were part of the NIED study cohort, we examined the associations between inflammatory markers including serum interleukin (IL) 1β, IL-6, C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) and type of vascular access. Unadjusted and multivariate-adjusted linear regression models were used. In addition, time-dependent regression model was used to assess the association between inflammatory markers and mortality. We observed that in the multivariate-adjusted model, inflammatory mediators interleukin-6 (IL-6), interleukin-1L-ß (IL-1ß), and C-reactive protein (CRP), the predicted value in hemodialysis patients, are lowest in patients with AVF and highest in central venous catheter (CVC) and AVG even in case-mix and malnutrition-inflammation complex syndrome (MICS)-adjusted models. IL-6 and CRP levels fall consistently in the same patients when AVG or CVC is changed to AVF and increase if the same patient changes access from AVF to AVG or CVC. Obesity is a risk factor for fistula failure and fistulas are associated with the lowest mortality compared with CVC and AVG. We did not find any statistically significant association between tumor necrosis factor-α (TNF- α) and vascular access outcomes. Higher levels of inflammatory mediators seen in CVC and AVG compared with AVF could potentially explain the higher mortality seen in patients with CVC and AVG compared with AVF.

BACKGROUND: Mineral and bone disorder (MBD) is common and associated with mortality in patients with chronic kidney disease (CKD) Given that disarrays in serum phosphorus (P) and parathyroid hormone (PTH) levels and their changes over time are closely interrelated, modeling mortality-predictability of their combinations may help improve CKD patient management. METHODS: A historical cohort study was undertaken to evaluate the joint effect of serum P and PTH levels on mortality in 107,299 chronic hemodialysis (HD) patients. Changes in serum P and PTH levels over 6months, in particular discordant changes, were also modeled with mortality. RESULTS: HD patients were 64±15 (mean±SD)years old and included 45% women, 33% African-American, and 59% diabetic. Compared with serum P level ≥7.0mg/dL and PTH level ≥600pg/mL, adjusted hazard ratio (HR) tended to be lowest in patients with serum P level of 3.5-

BACKGROUND: In contrast to the general population, higher body mass index (BMI) is associated with greater survival in patients receiving hemodialysis (HD; obesity paradox). We hypothesized that this paradoxical association between BMI and death may be modified by age and dialysis vintage. STUDY DESIGN: Retrospective observational study using a large HD patient cohort. SETTING & PARTICIPANTS: 123,383 maintenance HD patients treated in DaVita dialysis clinics between July 1, 2001, and June 30, 2006, with follow-up through September 30, 2009. PREDICTORS: Age, dialysis vintage, and time-averaged BMI. Time-averaged BMI was divided into 6 subgroups;  25kg/m(2) added no additional benefit. Based on dialysis vintage, incident HD patients had greater all-cause and cardiovascular survival benefit with a higher time-averaged BMI compared with the longer term HD patients. LIMITATIONS: Causality cannot be determined, and residual confounding cannot be excluded given the observational study design. CONCLUSIONS: Higher BMI is associated with lower death risk across all age and dialysis vintage groups. This benefit is more pronounced in incident HD patients and those younger than 65 years. Given the robustness of the survival advantage of higher BMI, examining interventions to maintain or even increase dry weight in HD patients irrespective of age and vintage are warranted.

In the general population, obesity is associated with increased cardiovascular risk and decreased survival. In patients with end-stage renal disease (ESRD), however, an obesity paradox or reverse epidemiology (to include lipid and hypertension paradoxes) has been consistently reported, i.e. a higher body mass index (BMI) is paradoxically associated with better survival. This survival advantage of large body size is relatively consistent for hemodialysis patients across racial and regional differences, although published results are mixed for peritoneal dialysis patients. Recent data indicate that both higher skeletal muscle mass and increased total body fat are protective, although there are mixed data on visceral (intra-abdominal) fat. The obesity paradox in ESRD is unlikely to be due to residual confounding alone and has biologic plausibility. Possible causes of the obesity paradox include protein-energy wasting and inflammation, time discrepancy among competitive risk factors (undernutrition versus overnutrition), hemodynamic stability, alteration of circulatory cytokines, sequestration of uremic toxin in adipose tissue, and endotoxin-lipoprotein interaction. The obesity paradox may have significant clinical implications in the management of ESRD patients especially if obese dialysis patients are forced to lose weight upon transplant wait-listing. Well-designed studies exploring the causes and consequences of the reverse epidemiology of cardiovascular risk factors, including the obesity paradox, among ESRD patients could provide more information on mechanisms. These could include controlled trials of nutritional and pharmacologic interventions to examine whether gain in lean body mass or even body fat can improve survival and quality of life in these patients.

BackgroundPrior studies show that African-American and Hispanic dialysis patients have lower mortality risk than whites. Recent age-stratified analyses suggest this survival advantage may be limited to younger age groups, but did not concurrently compare Hispanic, African-American, and white patients, nor account for differences in nutritional and inflammatory status as potential confounders. Minorities experience inequities in kidney transplantation access, but it is unknown whether these racial/ethnic disparities differ across age groups.MethodsThe associations between race/ethnicity with all-cause mortality and kidney transplantation were separately examined among 130,909 adult dialysis patients from a large national dialysis organization (entry period 2001-2006, follow-up through 2009) within 7 age categories using Cox proportional hazard models adjusted for case-mix and malnutrition and inflammatory surrogates.ResultsAfrican-Americans had similar mortality versus whites in younger age groups (18-40 years), but decreased mortality in older age groups (>40 years). In contrast, Hispanics had lower mortality versus whites across all ages. In sensitivity analyses using competing risk regression to account for differential kidney transplantation rates across racial/ethnic groups, the African-American survival advantage was limited to >60-years age categories. African-Americans and Hispanics were less likely to undergo kidney transplantation from all donor types versus whites across all ages, and these disparities were even more pronounced for living donor kidney transplantation (LDKT).ConclusionsHispanic dialysis patients have greater survival versus whites across all ages; in African-Americans, this survival advantage is limited to patients >40 years of age. Minorities are less likely to undergo kidney transplantation, particularly LDKT, across all ages.

BackgroundObservational studies have consistently demonstrated the survival benefits of a greater dialysis dose in maintenance hemodialysis (MHD) patients, whereas randomized controlled trials have shown conflicting results. The possible causal impact of dialysis dose on mortality needs to be investigated using rich cohort data analyzed with novel statistical methods such as marginal structural models (MSMs) that account for time-varying confounding and exposure.MethodsWe quantified the effect of delivered dose of hemodialysis (HD) [single-pool Kt/V (spKt/V)] on mortality risk in a contemporary cohort of 68,110 patients undergoing HD 3 times weekly (7/2001- 9/2005). We compared conventional Cox proportional hazard and MSM survival analyses, accounting for time-varying confounding by applying longitudinally modeled inverse-probability-of-dialysis-dose weights to each observation.ResultsIn conventional Cox models, baseline spKt/V showed a weak negative association with mortality, while higher time-averaged spKt/V was strongly associated with lower mortality risk. In MSM analyses, compared to a spKt/V range of 1.2 -

BACKGROUND: Abnormalities in serum alkaline phosphatase (ALP) and intact parathyroid hormone (PTH) concentrations, as biochemical markers of bone turnover in dialysis patients, correlate with increased mortality in maintenance hemodialysis (MHD) patients. Changes in bone turnover rate vary with age. The mortality predictability of serum ALP and PTH levels in MHD patients may be different across ages. METHODS: We examined differences across four age groups (18 to

It is not clear to what extent changes in blood pressure (BP) during hemodialysis affect or predict survival. Studying comparative outcomes of BP changes during hemodialysis can have major clinical implications including the impact on management strategies in hemodialysis patients. Here we undertook a retrospective cohort study of 113,255 hemodialysis patients over a 5-year period to evaluate an association between change in BP during hemodialysis and mortality. The change in BP was defined as post-hemodialysis minus pre-hemodialysis BP, and mean of BP change values during the hemodialysis session was used as a mortality predictor. The patients' average age was 61 years old and consisted of 45% women, 32% African-Americans and 58% diabetics. Over a median follow-up of 2.2 years, a total of 53,461 (47.2%) all-cause and 21,548 (25.7%) cardiovascular deaths occurred. In a fully adjusted Cox regression model with restricted cubic splines, there was a U-shaped association between change in systolic BP and all-cause mortality. Post-dialytic drops in systolic BP between -30 and 0 mm Hg were associated with greater survival, but large decreases of systolic BP (more than -30 mm Hg) and any increase in systolic BP (over 0 mm Hg) were related to increased mortality. Peak survival was found at a change in systolic BP of -14 mm Hg. The U-shaped association was also found for cardiovascular mortality. Thus, modest declines in BP after hemodialysis are associated with the greatest survival, whereas any rise or large decline in BP is associated with worsened survival.

Diabetes mellitus (DM) is the most common cause of end-stage kidney disease and a major risk of morbidity and mortality. It is not clear whether medical management of DM has any significant beneficial effect on clinical outcomes at the end-stage of diabetic nephropathy with full-blown micro- and macro-angiopathic complications. Both loss of kidney function and dialysis treatment interfere with glucose homeostasis and confound glycemic control. Given the unique nature of uremic milieu and dialysis therapy related alterations, there have been some debates about reliance on the conventional measures of glycemic control, in particular the clinical relevance of hemoglobin A1c and its recommended target range of