Low Serum Concentration of Obestatin as a Predictor of Mortality in Maintenance Hemodialysis Patients

Obestatin, a proposed anorexigenic gut hormone, has been shown to have a number of beneficial cardiotropic effects in experimental studies. We hypothesized that obestatin alteration in hemodialysis patients may link to clinical outcomes. This cross-sectional study with prospective followup for almost 4 years was performed on 94 prevalent hemodialysis patients. Obestatin, leptin, proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6, and various nutritional markers were measured. Patients with low obestatin levels, defined as a level less than median, had a worse all-cause mortality and cardiovascular mortality. The crude all-cause (HR 2.23, 95% CI 1.17 to 4.24) and cardiovascular mortality hazard ratios (HR 4.03, 95% CI 1.27 to 12.76) in these patients continued to be significant after adjustment for various confounders for all-cause mortality. Across the four obestatin-TNF-α categories, the group with low obestatin and high TNF-α (above median level) exhibited a worse outcome in both all-cause mortality and cardiovascular mortality. Clinical characteristics of patients in low obestatin high TNF-α group did not differ from other obestatin-TNF-α categorized groups. In summary, low serum obestatin concentration is an independent predictor of mortality in prevalent hemodialysis patients. Novel interactions were observed between obestatin and TNF-α, which were associated with mortality risk, especially those due to cardiovascular causes

LONGITUDINAL CHANGES IN PHASE ANGLE REFLECT CHANGES IN SERUM IL-6 LEVELS IN MAINTENANCE HEMODIALYSIS PATIENTS

We hypothesized that longitudinal changes in phase angle (PA) may have independent associations with changes in inflammatory parameters over time and consequently with long-term survival in maintenance hemodialysis (MHD) patients.Dietary energy and protein intake, biochemical markers of nutrition, body composition (anthropometry and bioimpedance analysis) and IL-6 as inflammatory marker, were measured at baseline and at 6, 12, 18 and 24 months following enrollment, in 101 prevalent hemodialysis patients (37% women) with a mean age of 64.6±11.5 years. Observation of this cohort was continued over 3 additional years.Longitudinally, 1O increase in PA over time, controlling for demographic and clinical parameters, was associated with a delay in longitudinal elevation of IL-6 (linear estimate: -2.11 (95% CI: -3.47; -0.75) pg/ml/mo; p=0.002 for PA X Time interaction). A decrease or increase in PA over time was associated with inverse linear changes in IL-6 levels (adjusted r=-0.305, p=0.005) and correspondingly with higher or lower death risk. For each 1O increase in PA, the crude and adjusted mortality hazard ratios using Cox models with effect of time varying risk were 0.62 (95% CI: 0.54; 0.71) and 0.61 (95% CI: 0.53; 0.71), respectively.In conclusion, longitudinal changes in PA appeared to be reliable in detecting changes in nutritional and inflammatory parameters over time - combination that may contribute to understanding of its prognostic bearing

Longitudinal study of leptin levels in chronic hemodialysis patients

<p>Abstract</p> <p>Background</p> <p>The influence of serum leptin levels on nutritional status and survival in chronic hemodialysis patients remained to be elucidated. We conducted a prospective longitudinal study of leptin levels and nutritional parameters to determine whether changes of serum leptin levels modify nutritional status and survival in a cohort of prevalent hemodialysis patients.</p> <p>Methods</p> <p>Leptin, dietary energy and protein intake, biochemical markers of nutrition and body composition (anthropometry and bioimpedance analysis) were measured at baseline and at 6, 12, 18 and 24 months following enrollment, in 101 prevalent hemodialysis patients (37% women) with a mean age of 64.6 ± 11.5 years. Observation of this cohort was continued over 2 additional years. Changes in repeated measures were evaluated, with adjustment for baseline differences in demographic and clinical parameters.</p> <p>Results</p> <p>Significant reduction of leptin levels with time were observed (linear estimate: -2.5010 ± 0.57 ng/ml/2y; p < 0.001) with a more rapid decline in leptin levels in the highest leptin tertile in both unadjusted (p = 0.007) and fully adjusted (p = 0.047) models. A significant reduction in body composition parameters over time was observed, but was not influenced by leptin (leptin-by-time interactions were not significant). No significant associations were noted between leptin levels and changes in dietary protein or energy intake, or laboratory nutritional markers. Finally, cumulative incidences of survival were unaffected by the baseline serum leptin levels.</p> <p>Conclusions</p> <p>Thus leptin levels reflect fat mass depots, rather than independently contributing to uremic anorexia or modifying nutritional status and/or survival in chronic hemodialysis patients. The importance of such information is high if leptin is contemplated as a potential therapeutic target in hemodialysis patients.</p