Natriuretic Peptides as Predictors of Protein-Energy Wasting in Hemodialysis Population.

OBJECTIVE: Imbalance between anabolism and catabolism is linked to cachexia and protein-energy wasting (PEW), especially in frail populations such as patients with chronic kidney disease. PEW is responsible of poor outcomes with increased morbidity and mortality. Several causes are involved in PEW such as insulin resistance, acidosis, or hyperparathyroidism. Natriuretic peptides (NPs) have recently been described as activators of resting energy expenditure through the induction of browning of white adipose tissue in rodents with chronic kidney disease. The present study was therefore implemented to investigate whether NPs could be associated with PEW criteria and predict clinical outcomes. METHODS: We quantified serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) in a prospective cohort of 231 patients undergoing maintenance hemodialysis and atrial natriuretic peptide in a subgroup of 35 patients. Body composition parameters were measured with bioimpedance spectroscopy. RESULTS: NT-proBNP was inversely associated with serum albumin, prealbumin, and body mass index and, conversely, positively associated with age and C-reactive protein. NT-proBNP as well as atrial natriuretic peptide were significantly higher in patients with PEW criteria. NT-proBNP was negatively associated with body fat mass. In multiple linear regression, NT-proBNP remained associated with body mass index. Kaplan-Meier analysis revealed a significant correlation between serum NT-proBNP concentrations and all-cause mortality and cardiovascular events. This association remained significant after multivariable Cox regression models adjusted for demographic factors and cardiovascular risk factors. CONCLUSION: Accumulation of NPs seems to be associated with poor nutritional status and reduced survival among hemodialysis patients. Further studies are needed to confirm this association using resting energy expenditure measurement and adipose tissue biopsy.

Accumulation of natriuretic peptides is associated with protein energy wasting and activation of browning in white adipose tissue in chronic kidney disease.

Protein energy wasting is a common feature of patients with chronic kidney disease (CKD) and is associated with poor outcomes. Protein energy wasting and cachexia, a severe form of protein energy wasting, are characterized by increased resting energy expenditure but the underlying mechanisms are unclear. Browning corresponds to the activation of inducible brown adipocytes in white adipose tissue and occurs in states of cachexia associated with hypermetabolic disease such as cancer. Here we tested the hypothesis that CKD-associated protein energy wasting could result from browning activation as a direct effect of the uremic environment on adipocytes. In a murine model of CKD (5/6 nephrectomy), there was increased resting energy expenditure, expression of uncoupling protein 1 (a thermogenic protein uncoupling oxidative phosphorylation in mitochondria) and citrate synthase activity (a proxy of mitochondrial density in white adipose tissue). Mice with CKD also exhibited increased levels of atrial natriuretic peptide, a well known activator of browning. The incubation of primary adipose cells with plasma from patients receiving dialysis treatment and having signs of protein energy wasting led to an increased synthesis of uncoupling protein 1. Similarly, primary adipose cells exposed to atrial natriuretic peptide at concentrations relevant of CKD led to a significant increase of uncoupling protein 1 content. Thus, accumulation of cardiac natriuretic peptides during CKD could contribute to the browning of white adipose tissue and protein energy wasting.

Serum levels of the adipokine zinc-alpha2-glycoprotein (ZAG) predict mortality in hemodialysis patients.

Wasting has been associated with increased cardiovascular and all-cause mortality in chronic kidney disease (CKD). We investigated whether serum zinc-alpha2-glycoprotein (ZAG), a potent cachectic and lipid-mobilizing factor that is increased in patients with CKD, predicts clinical outcomes in patients on chronic hemodialysis. We quantified serum ZAG at baseline in a prospective cohort of 252 patients undergoing maintenance hemodialysis. Serum ZAG concentrations were inversely associated with serum albumin, creatinine, and triglycerides and, conversely, positively associated with age. Although ZAG is strongly linked to protein energy wasting (PEW) in patients with cancer, higher ZAG concentrations were not associated with PEW in our cohort. During a mean study follow-up of 954 days, 49 patients died and 62 patients experienced a cardiovascular event. Kaplan-Meier analysis revealed a significant correlation between serum ZAG concentrations and all-cause mortality and cardiovascular events. In separate multivariable Cox regression models, serum ZAG concentrations remained significantly associated with all-cause mortality and cardiovascular events after adjustment for demographic factors (age, sex, and dialysis vintage), metabolic parameters (serum albumin, prealbumin, triglycerides, cholesterol, normalized protein catabolic rate, and body mass index), and cardiovascular risk factors (diabetes, dyslipidemia, history of cardiovascular disease, smoking, and diuretic use as a proxy of residual renal function). Thus, serum ZAG appears to be a strong and independent predictor of mortality and cardiovascular events in patients with end-stage renal disease. Further studies are necessary to confirm this association and to elucidate the underlying mechanisms.

Bone microarchitecture is more severely affected in patients on hemodialysis than in those receiving peritoneal dialysis.

We used high-resolution quantitative computed tomography to study the microarchitecture of bone in patients with chronic kidney disease on dialysis. We compared bone characteristics in 56 maintenance hemodialysis (21 women, 14 post-menopausal) and 23 peritoneal dialysis patients (9 women, 6 post-menopausal) to 79 healthy men and women from two cohorts matched for age, body mass index, gender, and menopausal status. All underwent dual-energy X-ray absorptiometry of the spine and hip to measure areal bone mineral density, and high-resolution peripheral quantitative computed tomography of the radius and tibia to measure volumetric bone mineral density and microarchitecture. When compared to their matched healthy controls, patients receiving hemodialysis and peritoneal dialysis had a significantly lower areal bone mineral density in the hip. Hemodialysis patients had significantly lower total, cortical, and trabecular volumetric bone mineral density at both sites. Hemodialysis patients had significantly lower trabecular volumetric bone mineral density and microarchitecture at the tibia than the peritoneal dialysis patients. Overall, peritoneal dialysis patients were less affected, their cortical thickness at the distal tibia being the only significant difference versus controls. Thus, we found more severe trabecular damage at the weight-bearing tibia in hemodialysis compared to peritoneal dialysis patients, but this latter finding needs confirmation in larger cohorts.

Influence of inflammation on total energy expenditure in hemodialysis patients.

BACKGROUND AND OBJECTIVES: Studies show that inflammation can contribute to an increase in resting energy expenditure in patients with chronic kidney disease; however, findings about total energy expenditure (TEE) have not been reported. The aim of this study was to evaluate the effects of inflammation on TEE and physical activity energy expenditure in hemodialysis (HD) patients. DESIGN: This was a cross-sectional study. SETTING: This study was conducted from Hôpital Edouard Herriot, Lyon, France. PATIENTS: This study included 24 HD patients and 18 healthy subjects. MAIN OUTCOME MEASURE: TEE and step counts were measured over a 7-day period by the SenseWear Pro2 Armband in 24 HD patients (15 patients with C-reactive protein <5 mg/L, aged 67.0 ± 14.7 years, and 9 with C-reactive protein >5 mg/L, aged 69.0 ± 18.0 years) and compared with 18 healthy subjects (62.3 ± 15.3 years). RESULTS: Mean estimated TEE measured with SenseWear Pro2 Armband was significantly lower (25.5 ± 4.1 kcal/kg/day) in patients with inflammation when compared with those without inflammation (32.0 ± 6.7 kcal/kg/day) and with healthy subjects (31.8 ± 7.0 kcal/kg/day) (P = .012). There was a difference in the physical activity (step counts) between patient groups (P < .05). Healthy subjects and patients without inflammation walked more (8,107 ± 5,419 and 6,016 ± 3,752 steps/day, respectively) as compared with patients with inflammation (2,801 ± 2,754 steps/day, P = .001). CONCLUSION: Our findings suggest that patients with inflammation have a lower TEE when compared with healthy subjects and patients without inflammation. TEE is influenced by physical activity because patients with inflammation appear to be less active.

Preserved residual renal function is associated with lower oxidative stress in peritoneal dialysis patients.

BACKGROUND: Residual renal function (RRF) correlates with survival in peritoneal dialysis (PD). We investigated the association between oxidative stress and RRF in PD. METHODS: Adequacy of dialysis, total and free malondialdehydes (MDA), and lipid hydroperoxides (LHP) were obtained from 23 stable PD patients. RESULTS: Free MDA level decreased with total weekly Kt/V urea (r = -0.51, P = 0.013) and urinary Kt/V (KRU) (r = -0.53, P = 0.009), but not with peritoneal Kt/V. Similar results were found with LHP level. In multivariate analysis, total weekly Kt/V urea and KRU remained associated with free MDA and LHP, independently of gender, nutritional or inflammatory status, and peritoneal permeability. CONCLUSION: A preserved RRF is associated with lower serum levels of lipid peroxidation products among PD patients.

New measurements of energy expenditure and physical activity in chronic kidney disease.

The accurate estimation of total daily energy expenditure (TEE) in chronic kidney patients is essential to allow the provision of nutritional requirements; however, it remains a challenge to collect actual physical activity and resting energy expenditure in maintenance dialysis patients. The direct measurement of TEE by direct calorimetry or doubly labeled water cannot be used easily so that, in clinical practice, TEE is usually estimated from resting energy expenditure and physical activity. Prediction equations may also be used to estimate resting energy expenditure; however, their use has been poorly documented in dialysis patients. Recently, a new system called SenseWear Armband (BodyMedia, Pittsburgh, PA) was developed to assess TEE, but so far no data have been published in chronic kidney disease patients. The aim of this review is to describe new measurements of energy expenditure and physical activity in chronic kidney disease patients.

[Body composition in maintenance dialysis patients]. / Mesure de la composition corporelle chez les patients dialysés chroniques.

The analysis of the body composition is of great importance in the follow-up of the dialysed patients, in order to evaluate the evolution of their nutritional state while taking account of their state of hydration. The problems are summarized by modifications of the various compartments in particular of the muscular mass, associated variations of the state of hydration, calling into question the constant ratios usually used, represented by a hydration of the lean body mass with 0,732, and a body hydration with 58%. The association of two independent techniques, or more, allowing measurements and the estimates of the various compartments (the hydration; fatty mass; mineral contents; the lean body mass) is the only way of obtaining results easy to interpret and reliable.

Is 3-Carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) a Clinically Relevant Uremic Toxin in Haemodialysis Patients?

3-Carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) is a metabolite of furan fatty acid and a marker of fish oil intake. CMPF is described as a protein-bound uremic toxin and interacts with free oxygen radicals, which can induce cell damages. However, the clinical consequences of CMPF accumulation in haemodialysis patients remain poorly documented. The aims of this study are to investigate potential association between CMPF levels and (i) biochemical and nutritional parameters; (ii) cardiovascular events and (iii) mortality. Two hundred and fifty-two patients undergoing maintenance haemodialysis were included. Routine clinical biochemistry tests and assay for CMPF by HPLC technique were performed at the inclusion. Body composition parameters were measured using a bioimpedance spectroscopy method. The enrolled patients were prospectively monitored for cardiovascular events and mortality. CMPF level was positively correlated with nutritional parameters and lean mass and is significantly higher in patients without protein-energy wasting. However, the multivariate linear regression analysis indicated that CMPF level was not independently associated with albumin, prealbumin, creatinemia and body mass index. Elevated serum CMPF was not associated with mortality and cardiovascular morbidity. Our results indicate that CMPF is not a relevant uremic toxin in haemodialysis and in contrast could be a marker of healthy diet and omega 3 intakes.

The Relationship Between Body Composition and Bone Quality Measured with HR-pQCT in Peritoneal Dialysis Patients.

BACKGROUND: Bone is known to be impaired in chronic kidney disease and dialysis patients. Recent studies have shown that body composition (fat mass and lean mass) may impact bone health. Some of these effects may be related to mediators that are secreted by adipose tissue. METHODS: The aim of this study was to evaluate the association between body composition (dual x-ray absorptiometry [DEXA]) and adipokines (leptin, adiponectin), with bone density and microarchitecture assessed with high-resolution peripheral quantitative computed tomography (HR-pQCT) in chronic peritoneal dialysis (PD) patients in a single-center prospective study. RESULTS: Twenty-three patients with a median age of 61 years and body mass index (BMI) of 27 kg/m2 were recruited. On univariate analysis, age was negatively associated with total volumetric bone mineral density (vBMD) (r = -0.75, p < 0.01), cortical vBMD (r = -0.85, p < 0.01), and cortical thickness (r = -0.71, p < 0.01). There was a negative association between leptin and cortical thickness (r = -0.48, p = 0.021). Fat mass (FM) was negatively correlated with cortical thickness (r = -0.52, p = 0.012). No association was found between bone parameters and dialysis duration, serum insulin, intact parathyroid hormone, osteocalcin, and adiponectin. The short dialysis vintage could in part explain the lack of correlation with bone parameters. In multivariate analysis, FM was significantly and negatively correlated with total vBMD, cortical and trabecular thickness. CONCLUSIONS: These data suggest that FM is negatively associated with bone quality in PD patients, supporting a relation between body composition and bone that is independent from other dialysis-associated complications. The relative contribution of the different fat deposits (visceral versus subcutaneous) needs to be assessed in future studies.

Design and development of an impedimetric-based system for the remote monitoring of home-based dialysis patients.

A key clinical challenge is to determine the desired 'dry weight' of a patient in order to terminate the dialysis procedure at the optimal moment and thus avoid the effects of over- and under-hydration. It has been found that the effects of haemodialysis on patients can be conveniently monitored using whole-body bioimpedance measurements. The identified need of assessing the hydrational status of patients undergoing haemodialysis at home gave rise to the present Dialydom (DIALYse à DOMicile) project. The aim of the project is to develop a convenient miniaturised impedance monitoring device for localised measurements (on the calf) in order to estimate an impedimetric hydrational index of the home-based patient, and to transmit this and other parameters to a remote clinical site. Many challenges must be overcome to develop a robust and valid home-based device. Some of these are presented in the paper.

[Influence of hemodialysis on total and free malondialdehyde measured by a new HPLC method]. / Influence de l'hémodialyse sur les concentrations de malonedialdéhyde total et libre, mesurées par une nouvelle technique HPLC spécifique.

Accurate evaluation of oxidative stress is needed for patients on chronic hemodialysis (HD), as cardiovascular risk level seems related to it. Oxidative stress is often evaluated by measuring an end product of lipoperoxidation named malondialdehyde (MDA). However, the most common technique for measuring MDA, the Thio Barbituric Acid Reactive Substances method (TBARS), is known to be sensitive but poorly specific. We measured true total and free plasma MDA in fifty-four unselected patients on long-term HD, before and after HD sessions, by a new, highly specific HPLC method. Total and free MDA were higher before than after dialysis. Essentially, free MDA was decreased by HD but its fractional decrease was lower than that of urea or creatinine. This confirms that, in fact, free MDA is more or less bound to low molecular weight compounds and/or suggests that MDA may be produced mainly during HD sessions. We propose this new tool to further explore the relationship between oxidative stress, HD and true MDA.

[Results of therapeutics strategy of protein-energy wasting in chronic hemodialysis: a prospective study during 12 months]. / Résultats des stratégies thérapeutiques au cours de la dénutrition en hémodialyse chronique: étude prospective sur 12 mois.

INTRODUCTION: Undernutrition (UN) in chronic hemodialysis (CHD) is a recurrent complication and constitutes a major public health problem. This work aims to evaluate the effects of our nutritional strategy (NS) developed among malnourished patients (pts) in CHD. This is a prospective observational study conducted for 12 months (M) in a cohort of 132 pts in CHD including 49 women, mean age 66 ± 16 years and the dialysis vintage 72 ± 74 months. This NS is based on the action of a multidisciplinary team; it provides for moderate UN pts one first phase of an optimization of protein and energy intake in the daily meals; then depending on the clinical course a second phase of oral supplementation at home. For severe UN pts, the optimization of daily meals and the oral supplements at home are reinforced with perdialytic oral supplementation. This modality was also prescribed for moderate UN pts with poor compliance at home. In case of loss of appetite, anorexia, gastrointestinal intolerance or inadequate oral intakes the relay is made by the intradialytic parenteral nutrition (IPN). Methods consist in the evaluation of the serum albumin (ALB), CRP, normalized PCR (nPCR), and Kt/V ratio of urea at baseline (day (D) 0) and at endpoint (M12). The ALB was measured by immunoturbidimetry. Three nutritional profiles were defined, severe UN if ALB ≤ 35 g/L, moderate UN if 35

Six years' experience with short daily hemodialysis: do the early improvements persist in the mid and long term?

Observational studies from several groups have shown consistent beneficial effects in patients treated with short daily hemodialysis (SDHD). The cardiovascular and nutritional changes appear during the first few months after the initiation of SDHD. An extensive review of 17 patients from a group of 36 ESRD patients treated for up to 6 years with SDHD was undertaken to compare the clinicobiologic results during the initial period of standard hemodialysis (3 x 4 hr/week) and the short daily hemodialysis period at 1 year (SDHD(1)) and subsequent years (SDHD(2)). The statistical analysis of the clinicobiologic data clearly shows that the initial favorable results obtained during the first year of SDHD do persist in the mid and long term, which shows the more physiologic nature of this dialytic approach. The amelioration of left ventricular hypertrophy is of particular interest, showing a regression of ventricular dilation during the first year followed by a reduction of interventricular septum and posterior wall thickness during the subsequent years.

Toward green dialysis: focus on water savings.

Hemodialysis is one of the most water and energy-hungry medical procedures, and thus represents a clear opportunity where improvements should be made concerning the consumption and wastage of water. Three levels were investigated on which there are potential savings: the precise adjustment of water production according to specific needs, the reuse of reverse osmosis rejected water, and finally the huge volumes of post-patient dialysate effluent. The "AURAL" (Association pour l'Utilisation du Rein Artificiel à Lyon), main unit in Lyon, was the site of investigation for this study, which cares for 173 chronic hemodialysis patients. Evaluation of the 3 levels described earlier was undertaken on this particular building, and on the water treatment currently used. Volumes of produced water can be improved by different hydraulic systems or by adjusting the pure water conductivity used for dialysis. Concerning the reject water, reuse for building sanitation became the focus of further attention. The technical feasibility, volume of saved water, and applicable work costs were considered. The results suggest that out of a possible 2834 m(3)/year of reject water, 1200 m(3)/year may be reused and return on investment recovered within 5.8 years. Finally, the reprocessing and feasibility of reuse of dialysate effluent were investigated. Initial calculations show that although technical solutions are available, such processing of the wastewater production is not profitable in the short term. Regarding the significant prior authorization and risk management analysis necessary for such a project, this avenue was pursued no further. From the perspective of a "green dialysis," the reuse of reject water into sanitation is both viable and profitable in our unit, and must be the next step of our project. More widely, improvements can be made by defining a more precise range of pure water conductivity for dialysis and by applying reuse water project to new or to be renovated units.

[Fluid overload and arterial hypertension in hemodialysis patients]. / Évaluation et traitement de la surcharge hydrosodée et de l'hypertension artérielle en hémodialyse.

The water sodium overload is a factor of morbi-mortality and its treatment is one of the markers of adequacy of the hemodialysis treatment. Its first clinical assessment was improved by tools such as echocardiography and ultrasonography of the inferior vena cava, the per-dialytic curve of plasma volume, measuring BNP or proBNP and by impedancemetry. The combination of the evaluation of these parameters and of the clinical situation allows one to assess the extracellular overload, the state of the blood volume and the potential of plasma refilling. The latter is a key factor of the per-dialytic hemodynamic tolerance. It is itself a determining factor in weight can be achieved at the end of the session. Getting the "dry" weight can require modifications of the prescriptions of the hemodialysis sessions, a filling by albumin even a drugs support. Finally, the overload treatment is the central part of the treatment of arterial hypertension, which has to benefit however often from antihypertensive treatment the profit of which is demonstrated.

[Home hemodialysis: the technical overview. A 2010 survey]. / Hémodialyse à domicile : le point de vue technique. Enquête 2010.

Compared to the daily work in dialysis units, home haemodialysis represents a particular task for the technical services of healthcare facilities. This survey concerns this modality of treatment of end-stage chronic renal failure, and was led to three objectives: to make a snapshot of the practices done by the technical staff, to point out significant differences, and to identify common issues. This is also an opportunity to discuss about the future of this treatment. Numbers of registries show a continuous decline of home haemodialysis during past decades. This could be explained by many factors, but on the other hand several points tend to forecast a renewed interest for this method of treatment. A questionnaire was sent to every technical service of health organizations dispensing dialysis in France. Seventeen health facilities providing home haemodialysis have sent back their information, representing 238 patients, that to say almost the totality of the patients of the country. These data were analysed, relevant indicators were sorted out, so that initial objectives could be completed. The results are explained as follows: site activities, procedures before and during patient installation, equipment, preventive visits, and corrective maintenance. In lack of a precise regulation on the technical support of these patients, significant differences of operations were noted and are detailed, as well as several common difficulties. All these elements can be used as a basis for the development of a practical guide intended to technical services. This work is voluntarily centered on the technical aspects, but other levers exist to revitalize this method.

[Secondary hyperparathyroidism and anemia. Effects of a calcimimetic on the control of anemia in chronic hemodialysed patients. Pilot Study]. / Hyperparathyroïdie secondaire et anémie. Effets d'un calcimimétique sur le contrôle de l'anémie des hémodialysés chroniques. Étude pilote.

UNLABELLED: The main cause of resistance to erythropoiesis-stimulating agents (ESA) used for treatment of anemia in chronic hemodialysed patients (CHP) is the iron deficiency, absolute or functional. Secondary hyperparathyroidism (SHPT) is a secondary factor of resistance. Indeed, it has been reported in the literature an improvement of anemia parameters after surgical parathyroidectomy (PTX). The objective of this study is to assess in CHP, the impact of the correction of SHPT by a calcimimetic, cinacalcet (CI), (which is considered as a pharmacological PTX) on the response to ESA, measured by the erythropoietin resistance index (ERI). Twenty-two CHP with severe SHPT documented by an intact parathyroid hormone (iPTH) above 800pg/mL were included in this prospective pilot study. Mineral bone metabolism, anemia and nutritional parameters were measured baseline and after 6 months of treatment by CI. The effect on anemia was assessed at the end of study by the ERI, the change in Hb concentration, and the proportion of patients with Hb levels above 11g/dL. RESULTS: At the end of study there was a significant decrease (M6 vs M0) in iPTH (1302 vs 674pg/mL or -48%, p=0.006), serum calcium (2.39 vs 2.15mmol/L or -10%), serum phosphate (2 vs 1.7mmol/L or -15%), serum calcium-phosphorus product (CaxP) (4.8 vs 3.8mmol(2)/L(2) or - 20% (p<0.05), and the number of patients with CaxP>4.4mmol(2)/L(2) (64 vs 32%, p<0.05). The level of bone alkaline phosphatase remained stable during the study (28 vs 27 IU/L). The Hb levels increased from 11 to 11.4g/dL, as did the proportion of patients whose Hb concentration reached 11g/dL or higher (50 vs 70%, p<0.05) without important change of the median weekly ESA dosis in the majority of patients, 18 cases (81%) vs four (19%). Two subgroups were identified from the median decreases in iPTH (delta iPTH) between M0 and M6, Group 1 (delta iPTH≥400pg/mL, n=10) and group 2 (delta iPTH<400pg/mL, n=12): in group 1, we found a correlation between the decrease in iPTH by CI and the stability or decrease in ERI (group 1), at comparable dose of dialysis, nutritional and iron intakes and inflammatory profiles; in group 2 without a significant effect of CI on PTH reduction the levels of ERI and ESA dosis were more elevated. CONCLUSION: A treatment by calcimimetic improves the control of anemia by ESA in CHP and interferes positively on a cause of secondary resistance to ESA represented by SHPT. The mechanism of these effects could be linked to the decreased of bone marrow fibrosis and inflammation and to the triptych formed by the reduction in iPTH, CaxP and phosphate.

Obestatin and ghrelin interplay in hemodialysis patients.

OBJECTIVE: Compounds involved in the regulation of appetite and body composition appear to be of interest in chronic kidney disease. The purpose of this study was to analyze plasma obestatin and acyl and des-acyl ghrelin in patients on hemodialysis (HD). METHODS: Fifty patients on HD (56.0% women, mean age 62.2 ± 15.2 y) were studied. Blood samples were collected during fasting, before a regular HD session. Serum acyl and des-acyl ghrelin levels, leptin, and obestatin were measured using enzyme immunometric assay methods. Anthropometric parameters, appetite score, and food intake were recorded. RESULTS: Patients showed elevated serum leptin (34.1 ± 30 ng/mL), normal acyl ghrelin (137 ± 116.5 pg/mL), high des-acyl ghrelin (670 ± 479 pg/mL), and low obestatin (2.0 ± 1.4 ng/mL) levels compared with healthy volunteers. According to body mass index (BMI), patients with a BMI >23 kg/m(2) had significantly lower plasma obestatin. In contrast, leptin levels were increased and acyl ghrelin tended to be higher in these patients. There was a strong positive correlation between obestatin and des-acyl ghrelin (r = 0.56, P = 0.0001) and inverse correlations between obestatin and BMI (r = -0.40, P = 0.007), waist circumference (r = -0.38, P = 0.024), and C-reactive protein (r = -0.29, P = 0.048). By multivariate analysis, obestatin was independently and positively correlated with des-acyl ghrelin (P = 0.01), but not with C-reactive protein, BMI, or waist circumference. CONCLUSION: In summary, patients on HD exhibited increased plasma levels of des-acyl ghrelin, normal acyl ghrelin levels, and low obestatin levels. In lean patients, the obestatin and des-acyl ghrelin levels were increased, suggesting that these hormones may influence appetite and body composition in patients on HD.