The present study aimed to asses the rela- is a 16kDa protein secreted by adipose tissue in tionship ..... Klein S, Coppack SW, Mohamed-Ali V, Landt M. Adipose.
Nephrol Dial Transplant (1998) 13: 2276–2280
Nephrology Dialysis Transplantation
Original Article
Plasma leptin concentration in kidney transplant patients during the early post-transplant period Franciszek Kokot, Marcin Adamczak and Andrzej Wie¸cek Department of Nephrology, Endocrinology and Metabolic Diseases, Silesian University School of Medicine, Katowice, Poland
Abstract Background. Leptin, is produced by adipose tissue and is presumed to be involved in the regulation of appetite and energy balance. The kidneys are involved in the inactivation of circulating leptin, and elevated plasma leptin concentrations were reported in uraemic patients. Finally, glucocorticosteroids as used in transplanted patients stimulate leptin secretion. Methods. The present study aimed to asses the relationship between plasma leptin concentration and kidney graft function in the early post-transplant period. We studied 40 successfully transplanted haemodialysed uraemic patients (27 males, 13 females, mean age 34.3±1.6 years, mean body mass index 22.5±0.5 kg/m2). The circadian rhythm of leptinaemia and insulinaemia was assessed twice: 2–4 days after kidney transplantation and 1 day before discharge from the hospital when graft function was good. Plasma leptin concentration was measured at 8 am, 4 pm, and 12 pm. The control group consisted of 21 healthy subjects (13 males, 8 females, mean age 39.4±2.5 years, mean body mass index 24.1±0.7 kg/m2). Results. Before kidney transplantation, patients had elevated plasma leptin and insulin levels. A positive correlation was found between BMI and leptinaemia and BMI and insulinaemia, respectively. An inverse relationship was found between leptinaemia and age. Successful kidney transplantation was followed by a significant decline of leptinaemia i.e. from 21.5±0.1 vs 7.1±1.3 ng/ml. Kidney transplantation did not influence the circadian rhythm of leptinaemia. Conclusion. Leptinaemia was not related to the excretory graft function or immunosuppression. In addition to renal excretory function, other factors must be involved in the post-transplant decline of leptinaemia. Key words: kidney transplantation; leptin; insulin
Introduction Malnutrition and loss of appetite are common features of chronic uraemia [1,2]. After successful kidney transplantation both the nutritional state and appetite usually improved markedly [2]. Leptin, the adipose tissue-specific ob gene product, is involved in the regulation of appetite and energy balance [3,4]. Leptin is a 16 kDa protein secreted by adipose tissue in proportion to fat stores [4]. Leptin receptors have been found in the choroid plexus and hypothalamus [5] where leptin appears to reduce synthesis and release of the neuropeptide Y [6 ]. In turn, neuropeptide Y is one of the most potent appetite stimulants yet demonstrated [6 ]. Thus leptin is presumed to be a powerful regulator of the satiety centre of the brain [6,7]. Leptin is released in a circadian pattern with the highest serum concentration observed at night [8]. Participation of increased leptin concentration at night in nocturnal inhibition of appetite seems likely [8]. The kidneys are involved in inactivation of circulating leptin [9,10]. This fact explains presence of elevated plasma leptin concentration in uraemic patients [9,11–15]. Taking into account the anorectic effects of leptin, involvement of this hormone in the pathogenesis of poor appetite and low food intake in uraemic patients seems very likely [7,16 ]. It is also well known that glucocorticosteroids, the most often used immunosuppressive drug in kidney transplant patients, stimulate leptin secretion [17–20] and that successful kidney transplantation is followed by normalization or even excessive appetite. These considerations prompted us to examine leptinaemia in kidney transplant recipients. The study was designed to asses the relationship between plasma leptin concentration and both kidney graft function and immunosuppression, respectively, during the early post-transplant period.
Material and methods Correspondence and offprint requests to: Prof. Dr hab. med. Franciszek Kokot, Department of Nephrology, Endocrinology and Metabolic Diseases, Silesian University School of Medicine, Francuska 20/24 Str., 40–027 Katowice, Poland.
A total of 40 patients after successful kidney transplantation were examined (27 male, 13 female, mean age 34.3±1.6 years, mean duration of haemodialysis therapy 35.4±4.6
© 1998 European Renal Association–European Dialysis and Transplant Association
Plasma leptin in kidney transplant patients
months, mean body mass index (BMI ) before kidney transplantation 22.5±0.5 kg/m2). The patients suffered from chronic glomerulonephritis (n=27), interstitial nephritis (n=3), polycystic kidney disease (n=3), amyloidosis, arterial hypertension, Alport syndrome (one patient each), unknown cause (n=4). The following protocol of immunosuppressive therapy was used: methyloprednisolon 500 mg intravenously for 3 days, then gradual reduction of the doses for the next 6 days, followed by prednisone p.o. 1 mg/kg b.w./day, azathioprine 2.5 mg/kg b.w./day, and cyclosporine A 3 mg/kg b.w./day (when diuresis was higher than 2 l per day). In two patients azathioprine was replaced by mycophenolate mofetil 2 g per day. In seven patients, therapy with azathioprine was discontinued because of leukopenia in the third week after transplantation. Plasma leptin, serum insulin and glucose concentration were estimated in blood samples withdrawn immediately before transplantation after 5–6 h of fasting. In addition, the circadian rhythm of leptinaemia, insulin and glucose serum concentration was estimated twice: 2–4 days after kidney transplantation and 1 day before discharge from the hospital when graft function was relatively good (mean 23.5±1.3 days after transplantation). The mean daily dose of prednisone, cyclosporine A and azathioprine on the last day of hospitalization were 39.0±1.7, 226.3±9.1 and 100.8±8.5 mg, respectively, and the mean cyclosporine A blood concentration was 175.6±16.2 ng/ml. For the estimation of the leptin circadian rhythm, blood samples were withdrawn at 8 am, 4 pm, and 12 pm. The control group consisted of 21 healthy subjects (13 males, 8 females, mean age 39.4±2.5 years, mean BMI 24.1±0.7 kg/m2). In control subjects the circadian rhythm of leptinaemia, insulinaemia and serum glucose concentrations (8 am, 4 pm, and 12 pm) and serum creatinine concentration (S-creatinine) were estimated on one occasion. Plasma leptin concentration was estimated with a radioimmunoassay method using kits from Linco Research Inc., USA (coefficient of intraassay and interassay variation was 7.1% and 10.8%, respectively). Plasma insulin concentrations were estimated with a radioimmunological method described in [21]. Plasma glucose and creatinine were estimated by routine methods used in our laboratory. Statistical evaluation of results was performed using Mann–Whitney U test and Wilcoxon matched pairs test. Correlation coefficients were calculated according the Kendall tau correlation test. Multiple regression analysis was also performed. Results are expressed as means±SEM.
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by more than ±1 ng/ml, while in four patients an actual increase (by 22.5, 11.3, 11.3 and 2.9 ng/ml, respectively) was noticed ( Figure 1). As shown in Table 1 in healthy subjects, the peak leptin concentration occurred at 12 pm (significantly higher versus the 8 am and 4 pm values, P
