Correlation of serum leptin concentrations with body composition and gender in Taiwanese hemodialysis patients without diabetes

OBJECTIVE: (1) To evaluate the impact of body composition and gender on serum leptin concentration in hemodialysis patients. (2) To study which marker of adiposity is most appropriate in Taiwanese hemodialysis patients without diabetes. (3) To compare the nutrition status between nonlean and lean subjects. PATIENTS AND METHODS: Serum leptin concentrations were measured by radioimmunoassay collected in 88 hemodialysis patients without diabetes. Bioimpedance analysis was performed to determine percent fat mass (%FM), lean body mass (LM), and total body water (TBW). Body mass index (BMI) was calculated as weight/height2. Albumin and transferrin were measured by standard laboratory methods. RESULTS: Serum leptin levels were more correlated with percent fat mass (r = 0.697; P < 0.001) than with body fat mass (r = 0.672; P < 0.001) or with BMI (r = 0.594; P < 0.001) in the group as a whole and in each subgroup when analyzed separately by gender. The mean (+/- SD) serum leptin levels were 32.5 +/- 34.3 ng mL(-1) in women subjects and 13.6 +/- 15.5 ng mL(-1) in men subjects (P < 0.001). Multiple regression analysis in all subjects revealed that serum leptin levels were independently affected by percent fat mass and gender. Adiposity corrected serum leptin, such as leptin/BMI, leptin/percent fat mass, and leptin/body fat mass was significantly different between sexes (P < 0.001). The significantly higher serum leptin concentrations in women than in men were observed in obese subjects with BMI > 25 kg/m2 (P < 0.001) as well as nonobese subjects with BMI < 25 kg/m2 (P < 0.05). There were no differences in lean mass and albumin between nonlean and lean subjects. CONCLUSION: Gender and adiposity had impact on serum leptin levels in hemodialysis patients without diabetes. In terms of adiposity, serum leptin levels had stronger correlation with percent fat mass than with body fat mass (FM) or BMI in Taiwanese hemodialysis patients. Steady-state serum leptin levels could serve as valuable clinical markers for the body adiposity in stable hemodialysis patients without diabetes. Protein malnutrition markers and lean mass should be checked in lean subjects for the evaluation of the protein stores of hemodialysis patients.     

Correlation of Serum Leptin Concentrations with Body Composition and Gender in Taiwanese Hemodialysis Patients without Diabetes

Objective.?(1) To evaluate the impact of body composition and gender on serum leptin concentration in hemodialysis patients. (2) To study which marker of adiposity is most appropriate in Taiwanese hemodialysis patients without diabetes. (3) To compare the nutrition status between nonlean and lean subjects. Patients and Methods.?Serum leptin concentrations were measured by radioimmunoassay collected in 88 hemodialysis patients without diabetes. Bioimpedance analysis was performed to determine percent fat mass (%FM), lean body mass (LM), and total body water (TBW). Body mass index (BMI) was calculated as weight/height². Albumin and transferrin were measured by standard laboratory methods. Results.?Serum leptin levels were more correlated with percent fat mass (r = 0.697; P<0.001) than with body fat mass (r = 0.672; P<0.001) or with BMI (r = 0.594; P<0.001) in the group as a whole and in each subgroup when analyzed separately by gender. The mean (±SD) serum leptin levels were 32.5 ± 34.3 ng mL^?1 in women subjects and 13.6 ± 15.5 ng mL^?1 in men subjects (P<0.001). Multiple regression analysis in all subjects revealed that serum leptin levels were independently affected by percent fat mass and gender. Adiposity corrected serum leptin, such as leptin/BMI, leptin/percent fat mass, and leptin/body fat mass was significantly different between sexes (P<0.001). The significantly higher serum leptin concentrations in women than in men were observed in obese subjects with BMI >25 kg/m² (P<0.001) as well as nonobese subjects with BMI<25 kg/m² (P<0.05). There were no differences in lean mass and albumin between nonlean and lean subjects. Conclusion.?Gender and adiposity had impact on serum leptin levels in hemodialysis patients without diabetes. In terms of adiposity, serum leptin levels had stronger correlation with percent fat mass than with body fat mass (FM) or BMI in Taiwanese hemodialysis patients. Steady-state serum leptin levels could serve as valuable clinical markers for the body adiposity in stable hemodialysis patients without diabetes. Protein malnutrition markers and lean mass should be checked in lean subjects for the evaluation of the protein stores of hemodialysis patients.     

Increased plasma leptin/fat ratio in patients with chronic renal failure: a cause of malnutrition?

Background: Protein-energy malnutrition occurs in patients with chronic renal failure primarily due to loss of appetite. The ob gene protein, leptin, which is secreted by adipocytes, regulates body composition by lowering food intake. We have measured plasma leptin in undialysed and dialysed patients and in controls and the concentrations have been related to body composition, dietary intake, and biochemistry. Methods: Plasma leptin was measured by radioimmunoassay in 93 individuals in groups of undialysed, peritoneal dialysed, and haemodialysed patients and controls. Body composition was determined by DEXA. Results: Protein-energy malnutrition was evident in non-dialysed and dialysed patients from low lean or fat tissues, plasma albumin and transferrin. A third of the dialysis patients were eating less than prescribed intakes. Leptin relative to total fat mass (ng/ml/kg) was significantly greater for patients than for controls, particularly the dialysed patients. Leptin was highly correlated with total, arm, leg, and all other fat measurements, e.g. r for leptin vs% total fat was: undialysed 0.88, PD 0.81, HD 0.93, and controls 0.83 (P <0.0001 for all). Dialysis patients with the highest leptin/fat mass ratio had low protein intakes and significantly lower lean tissue mass. Leptin/fat ratio correlated inversely with dietary intake e.g. with protein intake in g/day an marginally in g/kg of ideal weight/day. Leptin concentration was unrelated to plasma creatinine or residual renal function or to the protein 'nutritional indices', albumin and transferrin. Conclusion: Our data suggests that leptin is markedly increased in some patients with chronic renal failure. The association of increased leptin with low protein intake and loss of lean tissue is consistent with leptin contributing to malnutrition but a definitive role cannot be substantiated by this study. Key words: body composition; chronic renal failure; dialysis; dietary intake; fat; leptin      

Measurement of serum leptin in patients with chronic renal failure on hemodialysis.

BACKGROUND: Leptin, the product of the obese gene, is produced exclusively in fat cells. SUBJECTS, MATERIALS AND METHODS: To evaluate the clinical significance of measuring serum leptin in 56 patients with chronic renal failure on hemodialysis (HD), we measured leptin levels using radioimmunoassay in 34 normal volunteers and in 56 patients on HD. RESULTS: Normal serum leptin averaged 5.7 +/- 0.7 (mean +/- SEM) ng/ml, which correlated significantly (p < 0.001) with the body fat percentage as measured by bioelectrical impedance analysis. Serum leptin in HD patients ranged from 1.3 to 142 ng/ml. The mean serum leptin analyzed after the logarithmic conversion was 5.6 ng/ml, which was not significantly different from the normal control value, although the body fat percentage was significantly lower than normal volunteers. There was a significant (p < 0.01) positive correlation between body fat percentage and serum leptin in both normal controls and HD patients. The slope of the regression curve was steeper in HD patients than in normal controls. CONCLUSION: (1) serum leptin levels to body fat mass are significantly higher in HD patients than controls; (2) the variability is much wider in HD patients; and (3) a significant relation exists between percent body fat and log serum leptin, the relation being steeper in HD patients than in controls.     

The plasma leptin concentration is closely associated with the body fat mass in nondiabetic uremic patients.

Plasma leptin is associated with the body mass index and, more precisely, with the body fat mass. Plasma leptin has been found to be elevated in uremic patients. This study aimed at investigating the plasma leptin concentration and associations between plasma leptin, body fat mass, and glomerular filtration rate in nondiabetic predialysis uremic patients and in nondiabetic patients on chronic hemodialysis. Plasma leptin, body fat mass, and creatinine clearance were measured in 22 predialysis uremic patients, 18 hemodialysis patients, and 24 healthy control subjects. The logarithmically transformed plasma leptin concentration was closely associated with the body fat mass in all groups (r = 0.93, r = 0.83, and r = 0.72, respectively; p < 0.000001, < 0.000002 and p < 0.001, respectively). In predialysis uremic patients the plasma leptin concentration was slightly elevated as compared with controls 10.4 (3.1-59.5) ng/ml versus 5.4 (1.6-47.5) ng/ml (median and range in parentheses; p < 0. 05), whereas the plasma leptin concentration was normal in hemodialysis patients. Plasma leptin was not significantly associated with the creatinine clearance in predialysis patients. In conclusion; the glomerular filtration rate seemed to have a limited influence on the plasma leptin concentration in nondiabetic uremic subjects matched by body fat mass to controls. The plasma leptin concentration was closely associated with the body fat mass, and the leptin level might, therefore, be useful as an indicator of the fat mass in nondiabetic uremic patients.     

Baseline leptin levels predict change in leptin levels during weight loss in obese breast cancer survivors

Leptin is an adipocyte-derived hormone involved in regulation of satiety, and it also appears to have a role in breast cancer risk. Leptin therefore might be a useful indicator of the potential preventive effects of weight loss in breast cancer survivors. In this study we examined whether the change in leptin levels could be predicted by weight loss in obese breast cancer survivors. The subjects in this study were participating in a randomized trial of an individualized approach towards weight loss in Detroit, MI. Breast cancer survivors (body mass index of 30-44 kg/m(2)) were enrolled and fasting blood samples were obtained for leptin analysis over 1 year of study. Leptin levels were available from at least two time points for 36 women, and weight change ranged from a gain of 11% to a loss of 25% of baseline weight. Using a repeated-measures regression model, both baseline leptin level and concurrent percent body fat were found to synergistically predict leptin levels. Thus, for women with the same body fat, those with higher baseline leptin levels are predicted to exhibit smaller decreases in leptin with weight loss. Similar results were obtained for body weight and body weight change, but the associations with body fat were stronger. Breast cancer survivors with initially higher leptin levels may differ with regard to regulation of change in leptin during weight loss resulting in relatively smaller changes in leptin with equivalent amounts of weight loss.     

Plasma immunoreactive leptin and neuropeptide Y levels in kidney transplant patients

Leptin and neuropeptide Y (NPY) seem to play an important role in food intake and energy expenditure. Leptin is secreted by adipose tissue in proportion fo fat stores and is presumed to be an important anorectic hormone. NPY is produced by the hypothalamus, and in contrast to leptin, is one of the most potent appetite stimulants yet demonstrated. On the other hand, in most patients increased appetite is present after successful kidney transplantation. Finally, a stimulatory effect of glucocorticoids on leptin secretion was reported. The present study aimed to assess the relationship between plasma leptin and NPY levels and body mass index (BMI) in haemodialyzed patients (HDP) with chronic renal failure and in kidney transplant patients (KTP). In both groups, BMI was of the same magnitude as in healthy controls. Despite the presence of a normal BMI, leptin levels in KTP (25.2 +/- 3.6 ng/ml) and in HDP with chronic renal failure (25.3 +/- 4.2 ng/ml) were higher than in controls (11.7 +/- 1.8 ng/ml). The mean plasma NPY level in KTP (168.0 +/- 10.3 pg/ml) was significantly higher (p < 0. 01) than in controls (70.7 +/- 5.9 pg/ml) and in HDP (77.0 +/- 5.7 pg/ml). In all examined groups, a significant positive correlation was found between leptinaemia and BMI. Conclusions: (1) KTP are characterized by significantly elevated leptinaemia in spite of a normal BMI. In KTP this increased leptinaemia does not seem to be dependent only upon the fat mass and the kind and dosis of immunosuppressive therapy. (2) Similarly to healthy subjects, female KTP and HDP show markedly higher leptinaemia than males. (3) In contrast to healthy subjects and HDP, KTP are characterized by significantly elevated plasma NPY levels.     

Leptin in peritoneal dialysate from continuous ambulatory peritoneal dialysis patients.

The adipocyte-derived hormone leptin is the 16-kd product of the ob gene that regulates food intake and body weight. Plasma leptin level is elevated in patients with chronic renal failure, partly because of impaired clearance through the kidney. In this study, we examined whether leptin is cleared into peritoneal dialysate in patients with end-stage renal disease treated by continuous ambulatory peritoneal dialysis (CAPD). The subjects were 46 CAPD patients and 67 age- and gender-matched healthy subjects. Leptin concentration in peritoneal dialysate from CAPD patients was measurable by a sensitive enzyme-linked immunosorbent assay (ELISA), and the daily loss of leptin by the peritoneal route was estimated to correspond to the amount contained in approximately 2 L plasma. Dialysate leptin concentration correlated positively with plasma leptin level and with percent body fat measured by dual-energy X-ray absorptiometry. The dialysate-to-plasma (D/P) ratio of leptin concentration was twice higher than expected from its molecular weight. D/P ratios of beta2-microglobulin, albumin, and transferrin showed strong correlations with each other (r = 0.768 to 0.801), whereas the correlation between D/P ratios of leptin and beta2-microglobulin was less impressive (r = 0.378). This was also the case with the relationship between apparent peritoneal clearances of these macromolecules, suggesting that dialysate leptin had some origins other than passive transport of plasma leptin. To test the hypothesis that abdominal visceral fat may contribute to the unexpectedly raised peritoneal dialysate leptin concentration, multiple regression analysis was performed. Leptin concentration in peritoneal dialysate showed significant association with plasma leptin level and D/P ratio of beta2-microglobulin, and it also showed an independent association with abdominal visceral fat but not with subcutaneous fat assessed by ultrasonography. These results showed that peritoneal dialysate from CAPD patients contained a significant amount of leptin, which derived presumably from both plasma and local visceral fat tissue.     

The concurrent accumulation of intra-abdominal and subcutaneous fat explains the association between insulin resistance and plasma leptin concentrations : distinct metabolic effects of two fat compartments

Obesity is associated with insulin resistance, particularly when body fat has a central distribution. However, insulin resistance also frequently occurs in apparently lean individuals. It has been proposed that these lean insulin-resistant individuals have greater amounts of body fat than lean insulin-sensitive subjects. Alternatively, their body fat distribution may be different. Obesity is associated with elevated plasma leptin levels, but some studies have suggested that insulin sensitivity is an additional determinant of circulating leptin concentrations. To examine how body fat distribution contributes to insulin sensitivity and how these variables are related to leptin levels, we studied 174 individuals (73 men, 101 women), a priori classified as lean insulin-sensitive (LIS, n = 56), lean insulin-resistant (LIR, n = 61), and obese insulin-resistant (OIR, n = 57) based on their BMI and insulin sensitivity index (S(I)). Whereas the BMI of the two lean groups did not differ, the S(I) of the LIR subjects was less than half that of the LIS group. The subcutaneous and intra-abdominal fat areas, determined by computed tomography, were 45 and 70% greater in the LIR subjects (P < 0.001) and 2.5- and 3-fold greater in the OIR group, as compared with the LIS group. Fasting plasma leptin levels were moderately increased in LIR subjects (10.8 +/- 7.1 vs. 8.1 +/- 6.4 ng/ml in LIS subjects; P < 0.001) and doubled in OIR subjects (21.9 +/- 15.5 ng/ml; P < 0.001). Because of the confounding effect of body fat, we examined the relationships between adiposity, insulin sensitivity, and leptin concentrations by multiple regression analysis. Intra-abdominal fat was the best variable predicting insulin sensitivity in both genders and explained 54% of the variance in S(I). This inverse relationship was nonlinear (r = -0.688). On the other hand, in both genders, fasting leptin levels were strongly associated with subcutaneous fat area (r = 0.760) but not with intra-abdominal fat. In line with these analyses, when LIS and LIR subjects were matched for subcutaneous fat area, age, and gender, they had similar leptin levels, whereas their intra-abdominal fat and insulin sensitivity remained different. Thus, accumulation of intra-abdominal fat correlates with insulin resistance, whereas subcutaneous fat deposition correlates with circulating leptin levels. We conclude that the concurrent increase in these two metabolically distinct fat compartments is a major explanation for the association between insulin resistance and elevated circulating leptin concentrations in lean and obese subjects.     

Body composition and cardiovascular risk in hemodialysis patients.

Death rate is unacceptably elevated in end-stage renal disease patients treated with hemodialysis. Excessive body fat, or obesity, is the well-known risk factor for cardiovascular disease and other health problems in the general population. However, hemodialysis patients with a higher body mass index (BMI) have a lower risk of death, as shown by many studies. There are several explanations for the paradox of BMI in dialysis patients. First, although body mass is composed of fat mass and fat-free mass (lean mass), it is unknown which is more important, fat mass or lean mass, in predicting outcome of hemodialysis patients. Second, it is also possible that functions of adipose tissue are altered in renal failure so that accumulation of body fat leads to less atherogenicity and beneficial properties become predominant. Third, an increased fat mass may be protective against death after harmful events. In this article, we explore these possibilities using either the data of our own cohort of hemodialysis patients or the existing registry data of Japan. We conclude that in hemodialysis patients, fat mass rather than lean mass plays a protective role against mortality, that the fat mass-adipocytokine relationship is altered, and that a low BMI is associated with increased risk of fatality after cardiovascular events rather than the risk of occurrence of such events.     

Leptin elimination in hyperleptinaemic peritoneal dialysis patients.

BACKGROUND: Elevated plasma concentrations of leptin, a hormone thought to regulate body composition by influencing food intake/metabolic rate, are prevalent in renal failure patients. The mechanism for these increases is not known, but evidence suggests that simple accumulation due to decreased elimination is insufficient explanation. METHODS: We studied the incidence of hyperleptinaemia in 28 end-stage renal disease patients treated with continuous ambulatory peritoneal dialysis (CAPD), compared with body-mass-index-and sex-matched controls. Results were separated by gender because women have higher leptin concentrations than men. Excretion of leptin and other substances in dialysis fluid was also studied. RESULTS: Hyperleptinaemia was prevalent in women CAPD subjects, but not in men. Plasma leptin concentrations correlated strongly with the daily excretion of leptin in dialysis fluid. Clearance of leptin in dialysis fluid was greater in men than women CAPD subjects. Single regression analysis found that fasting insulin, glucose content of dialysis fluid, plasma albumin, C-reactive protein, erythropoietin dose, urinary creatinine clearance and plasma beta2-microglobulin were not determinants of plasma leptin concentrations. Stepwise forward multiple regression, examining the dependence of plasma leptin on body mass index, renal creatinine clearance, plasma albumin, daily dialysis fluid glucose load, daily leptin in dialysis fluid, erythropoietin dose and plasma C-reactive protein found only erythropoietin dose as a consistent negative predictor of plasma leptin concentrations. CONCLUSIONS: The results suggest that hyperleptinaemia of CAPD was due to predisposing loss of renal elimination capacity combined with increased production due to obesity (more prevalent in women subjects of this study) and potentially female gender.     

Association of serum leptin with hypoventilation in human obesity

BACKGROUND: Leptin is a protein hormone produced by fat cells of mammals. It acts within the hypothalamus via a specific receptor to reduce appetite and increase energy expenditure. Plasma leptin levels correlate closely with total body fat mass operating via a central feedback mechanism. In human obesity serum leptin levels are up to four times higher than in lean subjects, indicating a failure of the feedback loop and central leptin resistance. In leptin deficient obese mice (ob/ob mice) leptin infusion reverses hypoventilation. It was hypothesised that a relative deficiency in CNS leptin, indicated by high circulating leptin levels, may be implicated in the pathogenesis of obesity hypoventilation syndrome (OHS). METHODS: Fasting morning leptin levels were measured in obese and non-obese patients with and without daytime hypercapnia (n=56). Sleep studies, anthropometric data, spirometric parameters, and awake arterial blood gas tensions were measured in each patient. RESULTS: In the whole group serum leptin levels correlated closely with % body fat (r=0.77). Obese hypercapnic patients (mean (SD) % body fat 43.8 (6.0)%) had higher fasting serum leptin levels than eucapnic patients (mean % body fat 40.8 (6.2)%), with mean (SD) leptin levels of 39.1 (17.9) and 21.4 (11.4) ng/ml, respectively (p<0.005). Serum leptin (odds ratio (OR) 1.12, 95% CI 1.03 to 1.22) was a better predictor than % body fat (OR 0.92, 95% CI 0.76 to 1.1) for the presence of hypercapnia. CONCLUSIONS: Hyperleptinaemia is associated with hypercapnic respiratory failure in obesity. Treatment with leptin or its analogues may have a role in OHS provided central leptin resistance can be overcome.     

Increases in serum leptin levels during peritoneal dialysis are associated with inflammation and a decrease in lean body mass

Leptin, secreted from fat cells, functions as a lipostat mechanism through modulation of satiety signals. Markedly elevated leptin levels have been documented in uremic patients, especially in those who are treated by peritoneal dialysis (PD). However, the role of hyperleptinemia in uremic patients is not clear, and it is not known whether elevated leptin levels contribute to uremic anorexia and changes in body composition. In this prospective study, serum leptin, C-reactive protein (CRP), plasma insulin, and body composition (dual-energy x-ray absorptiometry) were measured in 36 patients (53 +/- 1 yr) close to start and after about 1 yr of PD. In addition, markers of dialysis adequacy and urea kinetics were followed during treatment with PD. During PD, the total body fat mass (20.5 +/- 1.0 to 22.9 +/- 1.3 kg; P < 0.01), truncal fat mass (11.5 +/- 0.7 to 13. 2 +/- 0.9 kg; P < 0.001), and serum leptin levels (20.1 +/- 3.8 to 35.6 +/- 6.8 ng/ml; P < 0.01) increased markedly, especially in patients with diabetes mellitus. Twenty-five PD patients that lost lean body mass during PD had significantly (P < 0.05) elevated initial CRP levels (14 +/- 2 mg/L) compared to 11 patients (<10 mg/L) who gained lean body mass during PD. A significant increase in serum leptin levels (20.9 +/- 4.2 to 42.7 +/- 4.0 ng/ml; P < 0.001) was observed in those patients who lost lean body mass, whereas no such change (18.4 +/- 8.4 to 19.2 +/- 6.4 ng/ml) was observed in the patients that gained lean body mass during PD treatment. The present longitudinal results demonstrate that serum leptin level and body fat content increase markedly during PD, especially in diabetic patients. Patients that lost lean body mass during PD had higher initial CRP levels and increased their serum leptin levels significantly during PD compared to those patients that gained lean body mass. Additional studies are therefore needed to elucidate the role of hyperleptinemia and inflammation in causing anorexia, protein-malnutrition, and changes in body composition during treatment with PD.     

Hyperleptinemia in uremic patients undergoing conservative management, peritoneal dialysis, and hemodialysis: A comparative analysis.

We performed a cross-sectional study in a wide sample of patients with chronic renal failure undergoing conservative therapy (CTh) (n = 79), peritoneal dialysis (PD) (n = 75), and hemodialysis (HD) (n = 51), with the aim of analyzing the impact of the different modes of therapy on serum leptin levels. We used a multivariate approach, taking into consideration the potential effects of other epidemiological, dialysis-related, nutritional, and hormonal factors on serum leptin. Leptin levels were higher in patients treated with PD (median, 36 ng/mL) than in those undergoing CTh (10.8 ng/mL) or HD (5.4 ng/mL) (P < 0.0005). This difference persisted after controlling for gender, body mass index, and fasting insulin levels, suggesting that imbalances in these factors may only partially explain the differences found between the three modes of therapy. Leptin levels showed a significant negative correlation with peritoneal protein losses in PD patients but were poorly associated with factors such as proteinuria, daily peritoneal glucose absorption (PD), renal function, or adequacy of dialysis. Leptin and insulin-like growth factor-I (IGF-I) were significantly correlated in PD patients, but the study design did not allow for establishing a meaning for this correlation. In conclusion, serum leptin levels are increased in PD patients when compared with CTh or HD patients. Differences in gender distribution, fat mass, and insulin levels may partially explain these findings, but other undefined factors also may have a role in producing these results.     

Associations between plasma ghrelin levels and body composition in end-stage renal disease: a longitudinal study.

BACKGROUND: Ghrelin is a newly detected orexigenic gastric hormone that stimulates food intake. Increased levels of ghrelin are often found in disease states associated with wasting. Wasting is a common phenomenon in end-stage renal disease (ESRD) patients in whom elevated ghrelin levels have been reported. However, no data are available on the relationship between body composition and plasma ghrelin levels in this patient group. METHODS: The study population consisted of 108 (71 males) ESRD patients aged 53+/-12 years. Body composition, nutritional status (subjective global assessment), estimated protein intake (nPNA), plasma ghrelin, plasma insulin and serum leptin were evaluated close to the start of dialysis treatment. Twelve healthy subjects (nine males, 44+/-6 years) served as the control group. A longitudinal evaluation of changes in plasma ghrelin and body composition was performed in 52 of the patients after 12 months of dialysis treatment. RESULTS: Markedly elevated plasma ghrelin levels (843+/-485 vs 443+/-302 pg/ml; P<0.01) were observed in ESRD patients compared with controls. Basal plasma ghrelin levels correlated significantly with plasma insulin (R = -0.32; P<0.05), body mass index (R = -0.24; P<0.05), log serum leptin levels (R = -0.23; P<0.05) and truncal fat mass (R = -0.25; P<0.05). The longitudinal analysis of body composition demonstrated that whereas fat mass increased (23.7+/-8.6 to 25.3+/-9.9 kg; P<0.05) and plasma ghrelin levels decreased (855+/-429 to 693+/-408 pg/ml; P<0.05) significantly in peritoneal dialysis patients, no significant changes in either body composition or plasma ghrelin levels were found in patients treated by haemodialysis. CONCLUSION: Markedly elevated plasma ghrelin levels are found in advanced renal failure and correlate with fat mass, plasma insulin and serum leptin levels. Changes in plasma ghrelin during 12 months of peritoneal dialysis treatment are associated with changes in body composition.     

Role of leptin in reverse epidemiology in chronic kidney disease

Leptin is mainly produced by adipocytes and metabolized in the kidney. Leptin is taken up into the central nervous system by a saturable transport system, and controls appetite in rodents and in healthy subjects. Leptin acts on peripheral tissue and increases the inflammatory response by stimulating the production of tumor necrosis factor alpha, interleukin-6 and interleukin-12. In healthy humans, serum leptin concentration is related to the size of adipose tissue mass in the body. The majority of obese subjects have inappropriately high levels of circulating plasma leptin concentrations, indicating leptin resistance. In healthy subjects increased leptin concentration constitutes a biomarker for increased cardiovascular risk. On the other hand, a recent prospective long-term study in patients with chronic kidney disease stage 5 on hemodialysis therapy showed that reduced serum leptin concentration is an independent risk factor for mortality in these patients.     

Correlations between leptin, body composition, bone mineral density, and bone metabolism in kidney transplant recipients

INTRODUCTION: In kidney transplant recipients leptin levels are often elevated and bone mineral density (BMD) decreased. However, to date there are no about correlations between leptin and BMD in this population. It has been suggested that leptin is a predictor of BMD in postmenopausal women. Moreover, leptin acts as a marker of fat stores. We examined the relationships between leptinemia, some markers of nutritional status, BMD, and bone metabolism in kidney transplant recipients. We also assessed whether leptin was a significant and independent predictor of BMD in this population. METHODS: BMD and fat content (global, percentage, trunk) were measured using dual-energy X-ray absorptiometry in 27 kidney allograft recipients. Markers of bone turnover and leptin were studied using commercially available kits. RESULTS: Leptin correlated with the percentage of body fat, trunk fat, lean body mass, serum creatinine, and urea. Insulin growth factor binding protein 1 was negatively related to waist-hip ratio and global and trunk fat, whereas BMD of the lumbar spine was correlated with the daily dose of prednisone, azathioprine, cyclosporine trough levels, serum calcium, as well as osteoprotegerin level. CONCLUSIONS: Leptin levels are associated with graft function and body fat in kidney allograft recipients. Leptin is not related to nutritional status, BMD, or bone metabolism in kidney allograft recipients, but is associated with the current dosage of immunosuppressants and the serum calcium.     

Disturbed energy metabolism after lung and heart transplantation

Overweight, in combination with other cardiovascular risk factors, reduces survival after transplantation. The aim of this prospective study was to observe leptin, adiponectin, and energy intake as predictors of body mass index (BMI) and body composition and as risk factors associated with metabolic syndrome after lung and heart transplantation. After pre-operative baseline investigations, 35 lung and 59 heart recipients were followed and re-investigated two, six, and 12 months after transplantation. Linear regressions were performed to predict BMI and body composition. The lung recipients had a substantial weight gain after transplantation. Leptin increased, especially in the lung recipients and positively predicted BMI. Energy intake predicted BMI before and at two months after transplantation, but not after 12 months. Percentage trunk fat increased and lean mass decreased. Before transplantation, the dominant determinant of lean mass was adiponectin (positively associated), while after it was leptin (negatively associated), controlled for possible confounding variables (including prednisolone). Metabolic syndrome 12 months after transplantation was associated with higher leptin, greater weight gain without increased energy intake. After transplantation, a disturbed energy metabolism is indicated, where adiponectin and especially leptin are involved and a disadvantageous body composition is favored with increased body fat and decreased lean mass.     

Plasma leptin and insulin levels in weight-reduced obese women with normal body mass index: relationships with body composition and insulin.

Obesity is a complex disease with multiple features that has confounded efforts to unravel its pathophysiology. As a means of distinguishing primary from secondary characteristics, we compared levels of fasting plasma leptin and insulin in a cohort of weight-reduced obese women who have attained and maintained a normal BMI for more than 1 year with the levels in cohorts of never-obese and currently obese women. Weight-reduced obese women showed decreased plasma concentrations of leptin and insulin compared with obese women, but these levels remained significantly higher than those of never-obese women. Plasma leptin levels were highly correlated with plasma insulin levels (r = 0.60, P < 0.001). To further explore relationships with body composition, total body fat was determined by dual-energy X-ray absorptiometry and body fat distribution by computed tomography in subsets of these groups. Weight-reduced obese women had a significantly greater percent body fat and subcutaneous abdominal fat mass than did the never-obese women, and these were highly correlated with plasma leptin (r = 0.90, P < 0.001, and r = 0.52, P < 0.001, respectively). In these weight-reduced obese women, visceral fat mass was similar to that of the never-obese. The insulin sensitivity index and first-phase insulin response were also comparable. These results demonstrate that higher leptin levels in weight-reduced obese women are related to the higher total fat and particularly the subcutaneous fat masses. Normalization of visceral fat mass in the weight-reduced obese was accompanied by normalization of insulin sensitivity index and first-phase insulin response. This study suggests that increases in plasma leptin and insulin in obesity are secondary features of the obese state.     

Hyperleptinaemia of end-stage renal disease is corrected by renal transplantation

Background: Previous studies have reported that patients with end-stage renal disease (ESRD) have elevated plasma leptin concentrations, but the cause and significance of the elevations are unknown. We studied leptin concentrations in 29 adults undergoing renal transplantation, to determine if restoration of renal function reduced leptin concentrations in ESRD. Methods: Leptin concentrations were measured by radioimmunoassay in plasma specimens collected within 1 week before transplant, 6 days post-transplant, and 60 days post-transplant. Results: Plasma letpin concentrations were higher in both male and female ESRD patients compared with a control population of similar age and body mass index (BMI), but most of the disparity was due to a minority of patients with grossly elevated concentrations; the majority of ESRD patients had normal or near-normal leptin concentrations afer accounting for their adiposity with BMI. Six days after successful renal transplantation, average plasma leptin concentrations decreased to control levels. The grossly elevated pretransplant concentrations in a minority of patients were greatly reduced in relation to BMI, and the reduction persisted to 60 days post-transplant. The decrease in creatinine with transplant did not correlate with the decrease in leptin. Conclusions: These results demonstrate that restoration of renal function in ESRD patients reduces hyperleptinaemia, which provides further evidence of a cause/effect relationship between impaired renal function and abnormal leptin metabolism.