Size Matters: Body Composition and Outcomes in Maintenance Hemodialysis Patients

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Abstract

In hemodialysis patients a low body mass index (BMI) is correlated with an unfavorable clinical outcome, a phenomenon known as ‘reverse epidemiology’. Mechanisms underlying this observation are unclear. We propose the following: uremic toxin generation occurs predominantly in visceral organs and the mass of key uremiogenic viscera (gut, liver) relative to body weight is higher in small people. Consequently, the rate of uremic toxin generation per unit of BMI is higher in patients with a low BMI. Body water, mainly determined by muscle mass, serves as a dilution compartment for uremic toxins. Therefore, the concentration of uremic toxins is higher in small subjects. Uremic toxins are taken up by adipose and muscle tissues, subsequently metabolized and stored. Thus, the larger the ratio of fat and muscle mass to visceral mass, the lower the concentration of uremic toxins and the better the survival. To test this hypothesis, studies on uremic toxin kinetics in relation to body composition are needed.

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Effects of body size and body composition on survival in hemodialysis patients.

Maria Pappas, Srinivasan Beddhu, Nirupama Ramkumar … (2003)

It is unclear whether increased muscle mass or body fat confer the survival advantage in hemodialysis patients with high body-mass index (BMI). Twenty-four-hour urinary creatinine (UCr) excretion was used as a measure of muscle mass. The outcomes of hemodialysis patients with high BMI and normal or high muscle mass (inferred low body fat) and high BMI and low muscle mass (inferred high body fat) were studied to study the effects of body composition on outcomes. In 70,028 patients who initiated hemodialysis in the United States from January 1995 to December 1999 with measured creatinine clearances reported in the Medical Evidence form, all-cause and cardiovascular mortality were examined in Cox and parametric survival models. When compared with normal BMI (18.5 to 24.9 kg/m(2)) group, patients with high BMI (> or = 25 kg/m(2)) had lower hazard of death (hazard ratio [HR], 0.85; P 25th percentile (0.55 g/d), high BMI patients with UCr >0.55 g/d had lower hazard of all-cause (HR, 0.85; P < 0.001) and cardiovascular death (HR, 0.89; P < 0.001), and high BMI patients with UCr < or =0.55 g/d had higher hazard of all-cause death (HR, 1.14; P<0.001) and cardiovascular death (HR, 1.19; P <0.001). Both BMI and body composition are strong predictors of death. The protective effect conferred by high BMI is limited to those patients with normal or high muscle mass. High BMI patients with inferred high body fat have increased and not decreased mortality.

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Secretory factors from human adipose tissue and their functional role.

Hans Hauner (2005)

Obesity is characterized by an expanded adipose tissue mass. Recent data suggest that adipose tissue is a multi-functional organ rather than simply a passive storage site for excess energy. It has been clearly demonstrated that human adipose tissue produces a variety of secretory factors that exert multiple effects at both the local and the systemic level. To date, >100 products, covering a broad range of protein families as well as many fatty acids and prostaglandins, have been reported to be secreted by adipose tissue. The source of these secreted factors is not only mature fat cells but also poorly-identified cells present in the stromal-vascular fraction including macrophages. Secreted factors of particular interest include many cytokines or chemokines, such as TNF-alpha, IL-6, IL-8, as well as plasminogen activator inhibitor-1, angiotensin-II, leptin, and adiponectin. In the obese state the expression and secretion of these factors is disturbed. With the exception of adiponectin, most circulating factors are elevated. From this perspective, obesity can be described as a pro-inflammatory condition. In addition, regional differences in adipose expression of many of these factors have been found. There is now growing evidence that many secretory factors play an important role in the pathophysiology of the metabolic and cardiovascular complications of obesity. The question arising from these observations is how the secretory pattern of adipose tissue can be modified by dietary and pharmacological measures to reduce the health risks of obesity.

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Removal of P-cresol sulfate by hemodialysis.

Thomas Hostetter, Matthew Martinez, Natalie Recht … (2005)

Protein-bound solutes are poorly cleared by dialysis. Among the most extensively studied of these solutes is p-cresol, which has been shown to be toxic in vitro. This study examined the form in which p-cresol circulates and quantified its removal by hemodialysis. HPLC analysis of plasma from hemodialysis patients contained a peak whose mobility corresponded to synthetic p-cresol sulfate (PCS) but no detectable unconjugated p-cresol. Treatment with sulfatase resulted in recovery of this peak as p-cresol, confirming its identity. Subsequent studies compared the removal of PCS and another protein-bound solute, indican, to the removal of urea during clinical hemodialysis treatments. PCS and indican were 94 +/- 1% and 93 +/- 2% bound to plasma protein, respectively. Protein-binding caused a predictable decrease in measured dialytic clearance, which averaged 20 +/- 4 ml/min for PCS and 25 +/- 5 ml/min for indican as compared with 260 +/- 20 ml/min for urea. Volumes of distribution for the protein-bound solutes were greater than the plasma volume, averaging 15 +/- 7 L for PCS and 14 +/- 3 L for indican as compared with 37 +/- 7 for urea. Solute reduction ratios were 20 +/- 9% for PCS, 30 +/- 7% for indican, and 69 +/- 5% for urea. We conclude that p-cresol circulates in the form of its sulfate conjugate, PCS. PCS is poorly removed by hemodialysis because its clearance is limited by protein binding and the ratio of its volume of distribution to its clearance is high.

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Author and article information

Journal

Journal ID (publisher-id): BPU

Journal ID (nlm-ta): Blood Purif

Journal ID (doi): 10.1159/issn.0253-5068

Title: Blood Purification

Publisher: S. Karger AG

ISBN: 978-3-8055-8237-7

ISBN: 978-3-318-01434-1

ISSN (Print): 0253-5068

ISSN (Electronic): 1421-9735

Publication date Subscription-year: 2007

Publication date (Print): December 2006

Publication date (Electronic): 14 December 2006

Volume: 25

Issue: 1

Pages: 27-30

Affiliations

^aKrankenhaus der Barmherzigen Brüder, Graz, Austria; ^bRenal Research Institute, and ^cWeill Cornell Medical Center, New York-Presbyterian Hospital, New York, N.Y., USA

Article

Publisher ID: 96393 Other ID: Blood Purif 2007;25:27–30

DOI: 10.1159/000096393

PubMed ID: 17170533

SO-VID: 0a864243-cf8f-4628-b316-8a111bdbb25f

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Size Matters: Body Composition and Outcomes in Maintenance Hemodialysis Patients

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Abstract

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Karger: Nephrology

Most cited references 12

Effects of body size and body composition on survival in hemodialysis patients.

Secretory factors from human adipose tissue and their functional role.

Removal of P-cresol sulfate by hemodialysis.

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