Uremic Anorexia Research Articles

Anorexia In Hemodialysis Patients

Anorexia is characterized by a decrease in appetite. One-third of patients on hemodialysis(HD) have anorexia, which is characterized as the lack of the urge to eat. We essentially don't know how the disease started. Leptin, ghrelin, neuropeptides, inflammation, altered amino acid pattern, and uremic toxins as intermediate molecules have all been proposed as potential contributing factors. Malnutrition and cachexia are both facilitated by anorexia, which lowers oral protein and energy intake.
 There is no doubt that it lowers life quality.
 It is debatable if anorexia has any clinical significance as astandal one prognostic factor in HD patients. The therapy approach used to treat this crippling ailment may include regular dialysis sessions and nutritional advice.
 By bringing plasma branched-chain amino acids back to normal with branched-chain amino acid supplementation, anorexia may be reduced and energy and protein intake may be increased... Megestrol acetate's ability to stimulate appetite has to be supported by sufficient randomized studies. Melanocortin-receptor antagonists and subcutaneous ghrelin injection seem like potential treatment approaches.
 The uremic syndrome frequently leads to eating and appetite issues, which worsen malnutrition in dialysis patients. According to the findings, uremic anorexia could without the development of visceral and abdominal fatless food consumption. this type of obesity is characterized by The prevalence of intake and malnutrition) is higher in dialysis patients. than obesity brought on by excessive eating.

Status of water-soluble vitamins and neurological disorders in dialysis patients

The deficit of vitamins in patients receiving the long-term hemodialysis is discussed in the modern literature. Vitamin deficiency in a dialysis patient can be explained by the peculiarity of the diet recommendations, the need to take a number of medications, impaired absorption of vitamins in the digestive tract, poor appetite, uremic anorexia, depression, limited ability to buy and cook food, as well as losses of vitamins during the procedure of program hemodialysis. An analytical review of current (2011 and later) publications containing a comprehensive analysis of data on the status of water-soluble vitamins and its role in the development of neurological disorders in dialysis patients is provided. There is a high risk of deficiency of various water soluble vitamins and neurological disorders, such as vitamin B1 deficiency and thiamine deficiency encephalopathy and polyneuropathy, vitamin B6 deficiency and pyridoxine deficiency polyneuropathy, folic acid metabolism disorders, as well as vitamin B12 and the development of hyperhomocysteinemia, cognitive and depressive disorders, strokes, restless legs syndrome and dialysis polyneuropathy among the patients with end-stage chronic kidney disease and program hemodialysis. Vitamin C deficiency and the development of severe asthenic syndrome with insomnia and depression are described in dialysis patients. It seems necessary to revise the traditional nutritional approaches to the dialysis patients based on the analysis of the literature. Special attention is paid to the possible addition of such water-soluble vitamins as B1, B6, B9, B12 and C. Timely diagnosis of vitamin deficiency conditions and neurological disorders in patients on program hemodialysis, the development of methods for their correction and their introduction into clinical practice would improve the life expectancy and quality of life of dialysis patients.

Changes in gene expressions of hypothalamic neuropeptides controlling feeding behaviors in bilateral nephrectomized rats

Anorexia is one of the most widespread eating disorders that appears to contribute to malnutrition in patients with advanced kidney dysfunction. The changes of neuropeptides controlling feeding behaviors synthesized in the hypothalamus under several physiological condition could induce anorexia. While several mechanisms underlying uremic anorexia have been proposed, the changes of hypothalamic neuropeptides controlling feeding behaviors of uremic patients are poorly understood. The gene expressions of hypothalamic neuropeptides controlling feeding behaviors were evaluated after bilateral nephrectomy, which is a model of acute kidney dysfunction, by in situ hybridization histochemistry. Food consumption decreased markedly in bilateral nephrectomized rats. The mRNA levels of corticotrophin-releasing hormone, proopiomelanocortin, cocaine- and amphetamine-regulated transcript, which suppress feeding behavior, were significantly higher in bilateral nephrectomized rats than in sham-operated rats. On the other hand, the mRNA levels of Agouti-related peptide, neuropeptide Y, melanin-concentrating hormone, and orexin, which promote feeding behavior, were significantly lower in bilateral nephrectomized rats than in sham-operated rats. In addition, the plasma level of leptin, which has an anorexic effect, increased after bilateral nephrectomy. The results suggest that hypothalamic neuropeptides controlling feeding behaviors may be involved in the development of anorexia in bilateral nephrectomized rats. This report is the first step to elucidating the physiological mechanisms of anorexia in patients with kidney dysfunction.

Global Variation of Nutritional Status in Children Undergoing Chronic Peritoneal Dialysis: A Longitudinal Study of the International Pediatric Peritoneal Dialysis Network

While children approaching end-stage kidney disease (ESKD) are considered at risk of uremic anorexia and underweight they are also exposed to the global obesity epidemic. We sought to investigate the variation of nutritional status in children undergoing chronic peritoneal dialysis (CPD) around the globe. The distribution and course of body mass index (BMI) standard deviation score over time was examined prospectively in 1001 children and adolescents from 35 countries starting CPD who were followed in the International Pediatric PD Network (IPPN) Registry. The overall prevalence of underweight, and overweight/obesity at start of CPD was 8.9% and 19.7%, respectively. Underweight was most prevalent in South and Southeast Asia (20%), Central Europe (16.7%) and Turkey (15.2%), whereas overweight and obesity were most common in the Middle East (40%) and the US (33%). BMI SDS at PD initiation was associated positively with current eGFR and gastrostomy feeding prior to PD start. Over the course of PD BMI SDS tended to increase on CPD in underweight and normal weight children, whereas it decreased in initially overweight patients. In infancy, mortality risk was amplified by obesity, whereas in older children mortality was markedly increased in association with underweight. Both underweight and overweight are prevalent in pediatric ESKD, with the prevalence varying across the globe. Late dialysis start is associated with underweight, while enteral feeding can lead to obesity. Nutritional abnormalities tend to attenuate with time on dialysis. Mortality risk appears increased with obesity in infants and with underweight in older children.

Uremic anorexia and gastrointestinal motility dysfunction correlate with the changes of ghrelin system in hypothalamus

Ghrelin can act as a signal for meal initiation and play a role in the regulation of gastrointestinal (GI) motility via hypothalamic circuit. This study investigated the correlation between changes of hypothalamic ghrelin system and GI motility dysfunction and anorexia in rats with chronic renal failure (CRF). Sprague-Dawley (SD) rats (male/female 1:1, 180 ± 20 g) were randomly classified into a CRF group and control group (n = 8 per group). 5/6 nephrectomy was used to construct the CRF model. When plasma creatinine concentration (PCr) and blood urea nitrogen (BUN) in the CRF group were twice higher than the normal, food intake (g/24 h) and gastrointestinal interdigestive myoelectric complex (IMC) were detected. Then all rats were killed for assessment of the mRNA expression of ghrelin and growth hormone secretagogue receptor (GHS-R) in hypothalamus using reverse transcription-polymerase chain reaction. Analysis of variance, Student-Newman-Keuls-q-test and Correlation Analysis were used to do statistical analysis. P < 0.05 was considered as statistically significant. Compared to the control group, the CRF group was obviously decreased in the food intake (g/24 h), the phase III duration and amplitude and the ghrelin and GHS-R expression in the hypothalamus (P < 0.05). There was a positive correlation between them (P < 0.05). Changes of ghrelin and GHS-R in the hypothalamus correlate with gastrointestinal motility dysfunction and anorexia in rats with CRF.

Uremic anorexia and ghrelin expression in the amygdala

Background/aimsGhrelin can act as a signal for mealtime hunger and meal initiation. Amygdala is indispensable in appetitive behavior motivated by learned emotions. This study was to investigate the alteration of ghrelin in the amygdala of rats with chronic renal failure (CRF) and its relation with uremic anorexia. MethodsSD rats were randomly classified into CRF group and control group (n=16 per group). The CRF model was constructed using 5/6 nephrectomy. When plasma creatinine (PCr) and blood urea nitrogen (BUN) in the CRF group were twice more than the normal level, food intake (g/24h) was measured and then all rats were killed for detection of ghrelin protein expression in the amygdala using immunohistochemical analysis and mRNA expression using RT-PCT. Statistics was conducted with one-way analysis of variance, Student–Newman–Keuls-q test and correlation analysis. ResultsBy the 8th week after the surgery, the BUN and PCr of CRF rats exceeded double the normal level, and their food intake was obviously decreased compared with the controls (P<0.05). The protein and mRNA expression of ghrelin in the amygdala of CRF group were significantly reduced, and there was a positive correlation between this reduction and the decrease in food intake (P<0.05). ConclusionThe reduction of amygdala's ghrelin in CRF rats may be associated with uremic anorexia.

Longitudinal study of leptin levels in chronic hemodialysis patients

BackgroundThe influence of serum leptin levels on nutritional status and survival in chronic hemodialysis patients remained to be elucidated. We conducted a prospective longitudinal study of leptin levels and nutritional parameters to determine whether changes of serum leptin levels modify nutritional status and survival in a cohort of prevalent hemodialysis patients.MethodsLeptin, dietary energy and protein intake, biochemical markers of nutrition and body composition (anthropometry and bioimpedance analysis) were measured at baseline and at 6, 12, 18 and 24 months following enrollment, in 101 prevalent hemodialysis patients (37% women) with a mean age of 64.6 ± 11.5 years. Observation of this cohort was continued over 2 additional years. Changes in repeated measures were evaluated, with adjustment for baseline differences in demographic and clinical parameters.ResultsSignificant reduction of leptin levels with time were observed (linear estimate: -2.5010 ± 0.57 ng/ml/2y; p < 0.001) with a more rapid decline in leptin levels in the highest leptin tertile in both unadjusted (p = 0.007) and fully adjusted (p = 0.047) models. A significant reduction in body composition parameters over time was observed, but was not influenced by leptin (leptin-by-time interactions were not significant). No significant associations were noted between leptin levels and changes in dietary protein or energy intake, or laboratory nutritional markers. Finally, cumulative incidences of survival were unaffected by the baseline serum leptin levels.ConclusionsThus leptin levels reflect fat mass depots, rather than independently contributing to uremic anorexia or modifying nutritional status and/or survival in chronic hemodialysis patients. The importance of such information is high if leptin is contemplated as a potential therapeutic target in hemodialysis patients.

Identification of Patients With Eating Disorders: Clinical and Biochemical Signs of Appetite Loss in Dialysis Patients

Patients with chronic kidney disease (CKD) frequently experience loss of appetite (anorexia), which increases in severity during the disease progression. The optimal medical assessment of an anorectic patient depends on an appropriate knowledge of the associated signs and symptoms. Some of these signs are diagnostic of anorexia in CKD. The aim of the present review is to provide a general understanding of the consequences of anorexia in the CKD patient, while describing simple assessment methods of appetite loss easy to implement in the clinical setting. Early clinical and physical diagnostic signs associated with appetite loss, as well as the expected reflections in several blood biomarkers, are discussed. Finally, the potential role of sex hormones in modulating the severity of these symptoms is introduced as a platform toward the understanding of sex hormone action in regulating/treating uremic anorexia.

Relationship of Impaired Olfactory Function in ESRD to Malnutrition and Retained Uremic Molecules

Olfactory function is impaired in patients with end-stage renal disease (ESRD) and may contribute to uremic anorexia. Only limited correlations of olfactory function and nutritional status were reported. This study examines the relationship of impaired olfactory function to malnutrition and levels of the retained uremic solutes monomethylamine, ethylamine, indoxyl sulfate, and P-cresol sulfate. Cross-sectional observational study. 31 stable maintenance hemodialysis patients from an urban outpatient dialysis unit and 18 people with normal renal function participated. Nutritional status assigned by using Subjective Global Assessment (SGA) score; SGA score of 7 indicates normal nutritional status; SGA score of 5 to 6, mild malnutrition; and SGA score of 3 to 4, moderate malnutrition. The primary outcome is olfactory function, assessed using the University of Pennsylvania Smell Identification Test. Levels of retained uremic solutes were measured from a predialysis serum sample. Demographic data and laboratory values for nutritional status, adequacy of dialysis, and inflammation were collected. Mean smell scores were 34.9 +/- 1.4 for controls, 33.5 +/- 3.3 for patients with SGA score of 7, 28.3 +/- 5.8 for patients with SGA score of 5 to 6, and 27.9 +/- 4.4 for patients with SGA score of 3 to 4 (P < 0.001 comparing healthy patients with all patients with ESRD). There was no difference in mean smell scores for healthy controls and patients with SGA score of 7. However, patients with lower smell scores had significantly lower SGA scores (P = 0.02) and higher C-reactive protein levels (P = 0.02). Neither smell score nor nutritional status was associated with levels of retained uremic solutes. Small sample size, only cross-sectional associations can be described. Our results suggest an association between poor nutritional status and impaired olfactory function in patients with ESRD. Additional research is needed to discover the uremic toxins mediating these processes.

Role of fat mass and adipokines in chronic kidney disease

As traditional risk factors cannot alone explain the high prevalence and incidence of cardiovascular disease in chronic kidney disease, the complex of insulin resistance, oxidative stress, and endothelial dysfunction has increasingly been studied as an important non-traditional risk factor. Recent studies show that the adipose tissue is a complex organ with pleiotropic functions far beyond the mere storage of energy. Fat tissue secretes a number of adipokines including leptin and adiponectin, as well as cytokines, such as resistin, visfatin, tumor-necrosis factor-alpha and interleukin-6. Adipokine serum levels are markedly elevated in chronic kidney disease, likely due to a decreased renal excretion. Evidence suggests that these pluripotent signaling molecules may have multiple effects modulating insulin signaling, endothelial health and vascular outcome. Fat tissue is a storage depot for energy and a source of circulating signaling molecules. It plays an important role in the catabolic uremic milieu, and has been linked to systemic inflammation and uremic anorexia. Further research is needed to investigate the complex interactions between adipokine signaling networks and its effects on vascular health and outcome in chronic kidney disease.

Appetite Disorders in Uremia

Patients with chronic kidney disease frequently experience loss of appetite (anorexia), which increases in severity during the progression of the disease and may lead to protein-energy wasting, morbidity, and mortality. Anorexia represents a multiple, complex, and multifactorial disorder that may have its origin in renal failure (contemplating not only retention of uremic toxins but also peptides and cytokines) but that later on also involves metabolic abnormalities not yet corrected by dialysis therapy. This paper reviews current knowledge about the clinical signs of uremic anorexia as well as mechanisms involved. Based on megestrol acetate interventions and the recent observation that sex may modulate uremic appetite behavior, the potential role of sex hormones in treating chronic kidney disease anorexia needs to be further explored.

Brain Activation in Uremic Anorexia

This article reviews current knowledge about mechanisms responsible for uremic events, especially those that involve the central nervous system (CNS). Anorexia is a frequent complication of the uremic syndrome that contributes to malnutrition in patients on dialysis. Uremic anorexia has been associated with many factors. Traditionally, anorexia in dialysis patients has been regarded as a sign of uremic toxicity; therefore, 2 hypotheses have been proposed: the "middle molecule" and "peak concentration" hypotheses; both of these remain unproved. Recently, our group has proposed the tryptophan-serotonin hypothesis, which is based on a disorder in the amino acid profile that may be acquired when the patient is in uremic status. It is characterized by low concentrations of large neutral and branched chain amino acids in the cerebrospinal fluid. This situation permits a high level of tryptophan transport across the blood-brain barrier and enhances the synthesis of serotonin (the final target responsible for inhibiting appetite). The role of inflammation in the genesis of anorexia-malnutrition is also emphasized. In summary, in the CNS, factors associated with uremic anorexia include high levels within the cerebrospinal fluid of proinflammatory cytokines, leptin, and free tryptophan and serotonin (hyperserotoninergic-like syndrome), along with deficiency of neural nitric oxide (nNO) and disorders in various receptors such as melanocortin receptor-4 (MC4-R). Uremic anorexia is a complex complication associated with malnutrition and high levels of morbidity and mortality. Several uremia-acquired disorders in the CNS such as high cerebrospinal fluid levels of anorexigen substances and disorders in appetite regulator receptors may explain the lack of appetite.

Eating behavior disorders in uremia: a question of balance in appetite regulation.

Eating and appetite disorders are frequent complications of the uremic syndrome which contribute to malnutrition in dialysis patients. The data suggest that uremic anorexia may occur with or without abdominal and visceral fat accumulation despite a lower food intake. This form of obesity (i.e., with low food intake and malnutrition) is more common in dialysis patients than obesity with high food intake. This article reviews the current knowledge regarding mechanisms responsible for appetite regulation in normal conditions and in uremic patients. Anorexia in dialysis patients has been historically considered as a sign of uremic toxicity due to "inadequate" dialysis as judged by uncertain means ("middle molecule" accumulation, Kt/V, "peak-concentration hypothesis," and others). We propose the tryptophan-serotonin hypothesis, based on a uremia-induced disorder in patients' amino acid profile--low concentrations of large neutral and branched-chain amino acids with high tryptophan levels. A high rate of tryptophan transport across the blood-brain barrier increases the synthesis of serotonin, a major appetite inhibitor. Inflammation may also play a role in the genesis of anorexia and malnutrition. For example, silent infection with Helicobacter pylori may be a source of cytokines with cachectic action; its eradication improves appetite and nutrition. The evaluation of appetite should take into account cultural and social aspects. Uremic patients showed a universal trend to carbohydrate preference and red meat refusal compared to healthy people. In contrast, white meat was less problematic. Uremic patients also have a remarkable attraction for citrics and strong flavors in general. Eating preferences or refusals have been related to the predominance of some appetite peptide modulators. High levels of cholecystokinin (CCK) (a powerful anorexigen) are associated with early satiety for carbohydrates and neuropeptide Y (NPY) (an orexigen) with repeated food intake. Obesity and elevated body mass index often falsely suggest a good nutritional status. In uremic patients (a hyperinsulinemia state), disorders in the regulation of fat distribution (insulin, leptin, insulin-like growth factor [IGF]-1, fatty acids, and disorders in receptors for insulin, lipoprotein lipase, mitochondrial uncoupling protein-2, and beta 3 adrenoreceptors) may cause abdominal fat accumulation without an increase in appetite. Finally, appetite regulation in uremia is highly complex. Disorders in adipose tissue, gastrointestinal and neuropeptides, retained or hyperproduced inflammatory end products, and central nervous system changes may all play a role. Uremic anorexia may be explained by a hypothalamic hyperserotoninergic state derived from a high concentration of tryptophan and low branched-chain amino acids.

Serum Amino Acids in Dialysis Patients: The Tryptophan/Serotonin Disorder Hypothesis and Implications for Uremic Anorexia

Serum Amino Acids in Dialysis Patients: The Tryptophan/Serotonin Disorder Hypothesis and Implications for Uremic Anorexia

Uremic Anorexia: A Consequence of Persistently High Brain Serotonin Levels? The Tryptophan/Serotonin Disorder Hypothesis

Anorexia is a frequent part of uremic syndrome, contributing to malnutrition in dialysis patients. Many factors have been suggested as responsible for uremic anorexia. In this paper we formulate a new hypothesis to explain the appetite disorders in dialysis patients: "the tryptophan/serotonin disorder hypothesis." We review current knowledge of normal hunger-satiety cycle control and the disorders described in uremic patients. There are four phases in food intake regulation: (1) the gastric phase, during which food induces satiety through gastric distention and satiety peptide release; (2) the post absorptive phase, during which circulating compounds, including glucose and amino acids, cause satiety by hepatic receptors via the vagus nerve; (3) the hepatic phase, during which adenosine triphosphate (ATP) concentration is the main stimulus inducing hunger or satiety, with cytokines inhibiting ATP production; and (4) the central phase, during which appetite is regulated through peripheral (circulating plasma substances and neurotransmitters) and brain stimuli. Brain serotonin is the final target for peripheral mechanisms controlling appetite. High brain serotonin levels and a lower serotonin/dopamine ratio cause anorexia. Plasma and brain amino acid concentrations are recognized factors involved in neurotransmitter synthesis and appetite control. Tryptophan is the substrate of serotonin synthesis. High plasma levels of anorectics such as tryptophan (plasma and brain), cholecystokinin, tumor necrosis factor alpha, interleukin-1, and leptin, and deficiencies of nitric oxide and neuropeptide Y have been described in uremia; all increase intracerebral serotonin. We suggest that brain serotonin hyperproduction due to a uremic-dependent excess of tryptophan may be the final common pathway involved in the genesis of uremic anorexia. Various methods of ameliorating anorexia by decreasing the central effects of serotonin are proposed.

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.

Mechanisms of uremic suppression of appetite

Food intake is regulated by short-term satiety factors (gastric distension, amino acids, peptide hormones), as well as factors involved in long-term appetite regulation (leptin, insulin). Integration of the various signals takes place in the central nervous system (CNS). Appetite suppression in uremia is multifactorial and may include effects of uremia per se and of various comorbidity and psychosocial factors. Uremic anorexia is associated with elevated levels in plasma and CNS of short-term satiety factors (cholecystokinine, glucagon, serotonin, middle molecules) and factors that influence long-range regulation of appetite (leptin, insulin), but it is still unsettled to what extent these factors cause or contribute to appetite loss in uremic patients. Proinflammatory cytokines most probably also have a role in appetite suppression and malnutrition in patients with chronic renal failure.

Serum immunoreactive leptin concentration and its relation to the body fat content in chronic renal failure.

Leptin, secreted from fat cells, functions as a lipostat mechanism through modulation of satiety signals. The role of leptin in humans has been only partly revealed. However, obese patients have markedly elevated levels of this hormone, and in both normal-weight and obese subjects there is a direct correlation between serum leptin levels and the percentage of body fat. The aim of the present study was to investigate the role of leptin and its relation to body fat content in chronic renal failure (CRF), a disorder associated with decreased appetite. Serum leptin levels and body composition (dual-energy x-ray absorptiometry) were measured in a cohort of 59 patients with terminal CRF (creatinine clearance rate, 8 +/- 1 ml/min). Sixteen of the patients were re-evaluated after 12 mo of peritoneal dialysis treatment, and eight patients were re-evaluated after 12 mo of hemodialysis treatment. The mean serum leptin concentrations were markedly higher (mean +/- SEM) in patients with CRF than in healthy control subjects matched for gender and body mass index (25.7 +/- 5.2 ng/ml versus 8.4 +/- 0.9 ng/ml; P < 0.001). Patients with ongoing signs of inflammation (C-reactive protein > 10 mg/L) demonstrated higher serum leptin levels (41.9 +/- 13.7 ng/ml versus 18.6 +/- 4.2 ng/ml; P < 0.05) than patients with normal C-reactive protein. A strong positive correlation (rho = 0.83; P < 0.0001) was found between serum leptin concentrations and the percentage of body fat. After 12 mo of peritoneal dialysis, the amount of body fat increased markedly (19.0 +/- 1.5 to 25.1 +/- 2.2 kg; P < 0.001), and the changes in serum leptin concentrations correlated significantly (rho = 0.69; P < 0.01) to the changes in the body fat content. In contrast, no significant changes in either body fat content or serum leptin levels were recorded in the eight patients that were re-evaluated after 12 mo of hemodialysis. Serum leptin concentrations are approximately three times higher in patients with CRF compared with healthy control subjects with a similar body mass index. In this study, it is also demonstrated that serum leptin is a good marker for the body fat content in CRF patients and correlates strongly to changes in body fat during 12 mo of peritoneal dialysis. These findings suggest that serum leptin could serve as a valuable clinical marker for the body fat content in patients with CRF. Further studies are needed to verify the hypothesis that increased serum leptin concentrations may contribute to uremic anorexia.

Carbohydrate metabolism in the chronically uremic rat: II. In vivo glucose utilization

The sub-totally nephrectomized chronically uremic rat has been found to have significantly increased hepatic glucose-6-phosphate dehydrogenase activity and increased lipogenesis and glycoportein synthesis. Increased conversion of 14-C-D-glucose to 14-CO2, and increased plasma free fatty acid levels were also observed. The metabolic significance of these findings has been discussed, particularly with respect to the importance of the pentose shunt in this model. The influence of reduced diet intake, resulting from uremic anorexia, has been considered in light of changes observed. It is concluded that decreased food intake alone is unlikely to be responsible for the altered glucose utilization evident in this model.