Risk factors, such as hypertension, obesity and hypercholesterolemia, play an important role in the development of cardiovascular disease, not only in the general population but also in chronic kidney disease patients. In contrast to epidemiological data from the general population, in maintenance hemodialysis (MHD) patients low body mass index (BMI, defined as the weight in kilograms divided by height in meters squared) is correlated with an unfavorable clinical outcome, a phenomenon referred to as 'paradoxical' or 'reverse' epidemiology.

A decrease in mortality risk with a higher BMI was reported for the first time in a population of mostly young, non-diabetic patients treated with MHD in France during the 1970s [1]. Subsequently, several investigators found a significant inverse relationship between mortality risk and body size, unaffected by adjustments for co-morbidities, in prevalent and incident hemodialysis patients [2-4]. In a retrospective analysis of 10,000 MHD patients from the Dialysis Outcomes and Practice Patterns Study the relative risk for mortality was 0.84 in overweight patients and 0.78 in individuals with obesity as compared with patients in the BMI range of 23-


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Peter Kotanko, MD

Krankenhaus der Barmherzigen Brüder Department of Internal Medicine, Marschallgasse 12 AT-8020 Graz (Austria)

Tel. +43 316 706 70, Fax +43 316 706 7598, E-Mail [email protected]

24 kg/m2 [4]. In contrast, in a study based on 116 Japanese MHD patients [5] followed for 12 years, a BMI of >23 kg/ m2 was correlated with a lower survival rate than a BMI of 17.0-18.9 kg/m2.

Fat loss may be associated with a worse outcome in MHD patients. In a recent study [6] body fat was remea-sured (by means of near infrared interactance) in 411 MHD patients after 6 months. After adjustment for demographics and surrogates of muscle mass (MM) and inflammation (i.e., mid-arm muscle circumference, serum creatinine, and proinflammatory cytokines), a fat reduction of >1% was associated with a death risk 2 times (p = 0.004) that of patients who gained fat (>1%).

This is surprising because abdominal adiposity has shown associations with inflammation [7] and atherosclerosis [8] in MHD patients, just as in the general population. In particular, visceral adipose tissue (VAT) is associated with the prevalence of carotid atherosclerosis in MHD patients [ 8], However, no study in hemodialysis patients has reported on the differential effects of VAT and subcutaneous adipose tissue (SAT) on long-term survival.

Adipose tissue is a heterogeneous multifunctional organ rather than simply a passive storage site for excess energy. Its subcutaneous and visceral compartments present significant differences in morphology, physiology, metabolic activity, and hormonal sensitivity [9]. To date, more than 100 products have been reported to be secreted by adipose tissue [10], including TNF-a, IL-6, IL-8, plasminogen activator inhibitor-1, angiotensin-II, leptin, and adiponectin. Unlike adiponectin, most of these circulating factors are elevated in obese subjects. An increased local production of angiotensin-II contributes to insulin resistance and the metabolic syndrome. Leptin suppresses food intake and is considered a proin-flammatory cytokine [11]. It is conceivable that in a given individual the proportion of SAT to VAT may ultimately define the degree of proinflammatory activity of fat.

Using 24-hour urinary creatinine excretion as an indicator of MM, a study in a large cohort of MHD patients showed that the protective effect conferred by a high BMI is limited to those patients with normal or high MM [12]. By design, this study was limited to subjects with residual renal function. Although this study has been criticized on methodological grounds [13, 14], important insights into the interactions of BMI and MM were given.

The complex and poorly understood balance between the negative effects of adipose tissue (i.e. its proinflam-matory aspects) and the advantageous influence of an ad equate nutritional state may change over time. It was speculated that a high BMI is advantageous in the short term, but not over a longer period of time [15, 16], but the cause(s) of the improved survival in overweight and obese CHD patients remains obscure.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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