Free serum leptin but not bound leptin concentrations are elevated in patients with end‐stage renal disease

in chronic patients on haemodialysis with no apparent nutritional problems. Background. Leptin is a 16-kDa protein that is thought to be a regulator of food intake and body weight. Although total serum leptin levels have been reported Keywords: bound leptin; free leptin; haemodialysis; to be elevated in obese and normal weight patients nutritional status; post-dialysis; pre-dialysis with end-stage renal disease ( ESRD), it is not known whether serum-free leptin concentrations are also increased in patients with ESRD with no apparent nutritional problems. Furthermore, there are no data Introduction on how different dialysis modes (high-flux haemodiafiltration and low-flux dialysis) influence serum Malnutrition due to poor food intake is a common leptin subfractions. clinical problem in patients with end-stage renal disease Methods. We measured fasting serum free and bound ( ESRD) [1–2] and is associated with an increase in leptin levels in three groups of male subjects: patients morbidity and mortality in patients on haemodialysis on haemodiafiltration with high flux dialysers (n=11), treatment [3]. The role of leptin in controlling food patients on haemodialysis with low-flux dialysers (n= intake in humans is not clear, however, in rodents it 17) and healthy age (61±8 years) and BMI has been shown that leptin injection can decrease body (23.8±3.1 kg/m2) matched control subjects (n=28). weight and increase energy expenditure [4]. In animals Both leptin components were determined before and and humans, circulating total leptin levels are positively after a single dialysis session. correlated with body fat [5,6 ]. Moreover, it has been Results. Body mass indices were correlated with serum reported that patients with ESRD with [7,8] and free leptin levels in both patients (r=0.69, P<0.001) without ongoing dialysis treatment [9,10] have markand controls (r=0.77, P<0.001). Mean (SD) serum edly elevated total serum leptin levels without an free leptin levels were significantly higher in ESRD increase in body fat mass. Despite these elevated serum patients than in control subjects (91±33 vs 41± levels, it has been shown that patients with ESRD 21 pmol/l; P<0.01). Bound leptin levels did not differ have a significant lower expression of the leptin gene in both groups (0.67±0.12 vs 0.56±0.11 nmol/l, NS ). compared with body mass index (BMI ) matched conElevated serum-free leptin levels in ESRD patients trols, possibly through a negative feed back mechanism could be reduced by haemodiafiltration with high-flux due to a decreased plasma clearance [11]. In addition, membranes, but not with low-flux haemodialysis it has been reported that high-flux but not low-flux membranes.The former led to a reduction of initial dialysers can decrease total leptin levels [12–14]. serum free leptin values to 76±17% (P<0.01), whereas However, serum leptin has been noted to exist in a bound leptin remained unaffected. bound and free form [15]. Thus, we hypothesized, that Conclusion. Serum-free leptin levels are elevated in elevated total leptin levels in ESRD are due to elevated ESRD without any apparent effect on body weight. In free leptin levels which do not necessarily contribute contrast, serum bound leptin levels remain stable, thus to the anorexia found in uraemia. central feedback regulation via the bound form of the We measured free and bound leptin levels with hormone may serve as an alternative explanation in specific radioimmunoassays in male patients underthe regulation of food intake and energy expenditure going regular dialysis with no apparent nutritional problems and compared their levels with a BMI and age matched control group. Both components of the