malnutrition is common in patients with end stage renal disease ( esrd ) on hemodialysis ( hd ) . this may be associated with insufficient dietary intake , medication , inflammation , and/or their uremia status , which contribute to anorexia ( 1 - 4 ) . loss of appetite reduces the intake of dietary energy and other nutrients and leads to weight loss and malnutrition progression ( 4 ) . nevertheless , uremic toxins stimulate disorders of the central nervous system and adipose tissue ( 2 ) , which may affect diminished appetite ( 2 , 5 , 6 ) . leptin ,  a negative acute phase protein ,  is secreted by adipose tissue and acts on the hypothalamus in order to regulate food intake and energy expenditure ( 2 , 3 , 7 ) . it has been postulated that leptin plays an important role in inducing anorexia and malnutrition in uremic patients ( 2 ) , but the mechanisms by which it affects progressive malnutrition in kidney failure and its clinical significance are not clearly understood ( 3 ) . several studies have reported that serum levels of leptin are significantly increased in patients with chronic renal failure ( 3 , 9 ) . in a recent study , leptin level in a hd patient was not significantly different from the control ( 2 ) . some studies demonstrated that the high serum levels of c - reactive protein ( crp ) and cytokines , such as interleukin-1 ( il-1 ) and tumor necrosis factor- ( tnf- ) elevate leptin gene expression ( 3 , 4 , 10 ) , which may , in turn , play a role in inhibiting appetite during acute inflammatory conditions in renal failure patients ( 11 , 12 ) . in other studies , no correlation was identified between leptin level and body weight or nutritional status ( 4 , 13 , 14 ) . since data on the relationship between serum leptin and nutritional status in hemodialysis patients are limited , the present study was performed to investigate the association between serum leptin and crp levels and some nutritional factors in hemodialysis patients . forty - five patients with esrd ( 20 male and 25 female subjects , aged 43.2  13.1 years ) who were referred to the hemodialysis center of the imam ali teaching hospital , which is affiliated to the zahedan university of medical sciences ( zahedan , iran ) , were enrolled in this analytical descriptive study . all of the patients were dialyzed three times a week ( each session lasting 3 - 4 hours ) for at least three months with a minimum kt / v of 1.2 . a group of 40 healthy subjects ( 17 male and 23 female subjects , aged 38  12.6 years ) , who were matched for sex and age , were selected as controls during a medical visit to the internal clinic . the participants were not hospitalized or diagnosed with any infectious and inflammatory diseases , diabetes mellitus , cardiovascular ( cvd ) , liver , thyroid diseases , or cancer , in the past 3 months immediately prior to study enrollment . the nutritional status of the subjects was evaluated using both the food frequency questionnaire ( ffq ) and the calculation of the body mass index ( bmi ) . the ffq s reliability and validity as well the fewest intakes of daily serving of the various food groups represented in the food guide pyramid have been reported previously ( 15 ) . body weight and height were measured in the control group after 12 hours of fasting , and after hemodialysis in hd patients . bmi was categorized in accordance with the recommendations of the world health organization ( 16 ) . a bmi < 18.5 biochemical parameters including serum levels of blood urea nitrogen ( bun ) , uric acid , creatinine , total cholesterol , triglyceride , low density lipoprotein - cholesterol ( ldl - c ) , high density lipoprotein - cholesterol ( hdl - c ) , and albumin were measured with standard techniques by an automatic analyzer . serum leptin levels were assessed using commercial elisa ( enzyme linked immunosorbent assay ) kit ( human leptin elisa kit , ( biovendor [ cat no : rd191001100 ] , usa ) . this study was approved by the ethics committee of zahedan university of medical sciences ( approval date 4 january 2014 , number 6697 ) . the analysis was carried out using the spss statistical software package program ( version 18 for windows , chicago , usa ) . data were expressed as mean  sd and mean  sem with range , as appropriate . correlations among leptin and different parameters were determined using the spearman s correlation coefficient . a p value of < 0.05 was considered significant . the nutritional status of the subjects was evaluated using both the food frequency questionnaire ( ffq ) and the calculation of the body mass index ( bmi ) . the ffq s reliability and validity as well the fewest intakes of daily serving of the various food groups represented in the food guide pyramid have been reported previously ( 15 ) . body weight and height were measured in the control group after 12 hours of fasting , and after hemodialysis in hd patients . bmi was categorized in accordance with the recommendations of the world health organization ( 16 ) . a bmi < 18.5 after fasting overnight , blood samples were collected from all healthy subjects and patients immediately before hd . biochemical parameters including serum levels of blood urea nitrogen ( bun ) , uric acid , creatinine , total cholesterol , triglyceride , low density lipoprotein - cholesterol ( ldl - c ) , high density lipoprotein - cholesterol ( hdl - c ) , and albumin were measured with standard techniques by an automatic analyzer . serum leptin levels were assessed using commercial elisa ( enzyme linked immunosorbent assay ) kit ( human leptin elisa kit , ( biovendor [ cat no : rd191001100 ] , usa ) . this study was approved by the ethics committee of zahedan university of medical sciences ( approval date 4 january 2014 , number 6697 ) . the analysis was carried out using the spss statistical software package program ( version 18 for windows , chicago , usa ) . data were expressed as mean  sd and mean  sem with range , as appropriate . variables with normal distribution were compared using the student s t - test . correlations among leptin and different parameters were determined using the spearman s correlation coefficient . a p value of < 0.05 was considered significant . demographic and biochemical parameters of the hd patients and control group are exhibited in table 1 . serum leptin ( 16.3  2.7 ng / ml vs 23  5.2 ng / ml ; p < 0.05 ) and albumin ( 3.4  0.4 g / dl vs. 4.5  0.76 g / dl ; p < 0.0001 ) levels and bmi ( 22  2.1 kg / m vs. 24.7  4.9 kg / m ; p < 0.001 ) of hd patients were significantly lower , whereas serum crp ( 11.1  2.4 mg / l vs. 2.4  0.17 mg / l ; p < 0.0001 ) , bun ( 60.4  24.5 vs. 12.8  3.3 ; p < 0.0001 ) , creatinine ( 8.7  3.6 vs. 0.78  0.18 ; p < 0.0001 ) , and uric acid ( 6.3  1.7 vs. 5.7  1.5 ; p < 0.01 ) levels were higher than those in the control subjects . no significant differences in the lipid profile and blood pressure ( p > 0.05 ) readings were observed between the patients and controls . the causes of esrd were hypertension ( n = 16 ) , kidney stone ( n = 4 ) , lupus erythematosus ( n = 2 ) , polycystic kidney disease ( n = 4 ) , glomerulonephritis ( n = 8) , and unknown ( n = 11 ) . abbreviations : bmi , body mass index ; bun , blood urea nitrogen ; crp , c - reactive protein ; hdl - c , high - density lipoprotein - cholesterol ; ldl - c , low - density lipoprotein - cholesterol ; ns , not significant . crp and leptin levels were reported as mean  sem and range because the data were not normally distributed . as shown in table 2 , hd patients consumed less daily servings of the food groups compared to controls except for bread and cereals ( p < 0.0001 ) . there was positive correlation between serum levels of leptin and bmi ( r = 0.52 , p < 0.0001 ) ( figure 1 ) and albumin ( r = 0.71 , p < 0.05 ) ( figure 2 ) . serum leptin levels were not significantly correlated with crp level ( r = 0.11 , p = 0.46 ) , age ( r = 0.22 , p = 0.14 ) , duration of dialysis ( r = 0.21 , p = 0.16 ) , systolic blood pressure ( r = 0.02 , p = 0.91 ) , diastolic blood pressure ( r = 0.07 , p = 0.64 ) , and serum levels of bun ( r = 0.11 , p = 0.45 ) , creatinine ( r = -0.095 , p = 0.53 ) , uric acid ( r = 0.24 , p = 0.11 ) , cholesterol ( r = 0.05 , p = 0.72 ) , ldl ( r = 0.09 , p = 0.55 ) , hdl ( r = -0.18 , p = 0.24 ) , and triglycerides ( r = 0.03 , p = 0.86 ) . protein energy malnutrition ( pem ) is common in renal failure patients and progresses during the dialytic stage . mechanisms causing malnutrition in uremia are complex ( 1 , 3 , 17 ) . to date , many studies have demonstrated that insufficient weight gain , hypoalbuminemia , inflammation as well as calorie and protein metabolism disorders and low food intake are important markers , which are strongly associated with mortality risk in hemodialysis patients ( 1 - 4 , 6 , 18 ) . however , there have been few published studies on the relationship between serum leptin and nutritional factors in patients with chronic renal failure . thus , the objective of this study was to assess serum leptin level and its relationship with some nutritional factors in hemodialysis patients . in the present study , body weight and bmi of hd patients were significantly lower than those of controls , similar to previous studies ( 1 , 19 ) . serum albumin is also one of the other nutritional factors , which is sensitive to changes in nutritional intake ( 16 ) . in our study , albumin level was markedly lower than controls . some studies in hd patients have demonstrated a potential relationship between malnutrition and hypoalbuminemia , which depends on both nutrition and inflammation ( 1 , 3 , 17 , 20 , 21 ) . the excretion of albumin into the urine due to impaired renal function ( 16 ) and its leakage via the dialysis membrane are also independent factors that affect serum albumin level ( 1 ) . some studies have suggested that leptin may be associated with anorexia and protein energy loss that are frequently observed in patients with end - stage renal disease ( 3 , 17 ) . in this study , the mean serum leptin level was significantly decreased in hd patients , particularly in subjects with bmi < 18.5 kg / m and serum albumin level < 3.5 g / dl . additionally , serum leptin levels were found to positively correlate with bmi and serum albumin levels . similar data were previously obtained in other studies ( 2 , 3 , 22 ) , while several studies showed varying results . in some studies , no correlation was found between serum leptin levels and changes in body weight ( 12 - 14 , 19 , 23 ) and serum albumin ( 4 ) in patients with renal failure . in several reports , a positive correlation between the body fat value , especially abdominal fat accumulation  as a source of pro - inflammatory adipokine ,  and serum leptin has been demonstrated in hd patients ( 24 , 25 ) . inadequate food intake is also recognized as one of the important causes of malnutrition in hemodialysis patients ( 20 , 26 ) . earlier studies have reported that a majority of uremic patients undergoing hemodialysis suffer from nutritional disorders ( 1 , 2 , 4 , 20 ) . similarly , in the present study , patients consumed lower daily servings of milk and dairy products , fruit and vegetable compared to the control group , which might be associated with restriction of potassium and phosphorous intake in hd patients ( 27 ) . however , our previous findings also indicated that the intake of energy and protein was significantly decreased in hd patients compared to that in the control group ( 28 ) . leptin is one of the pituitary appetite regulating peptides , and its levels generally change in renal failure patients ( 3 , 11 , 12 ) . it has been suggested that the low levels of serum leptin may lead to a reduced appetite during hemodialysis treatment ( 2 ) . however , the role of leptin in regulating nutritional intake and energy expenditure has not been fully characterized . in our study , no correlation was found between leptin level and nutrient intake in hd patients , in agreement with earlier studies ( 4 , 13 , 14 ) . c - reactive protein ( crp ) is a positive acute phase protein and can be increased with any kind of infection / inflammation ( 1 , 3 ) . since increased serum crp inhibits the serum albumin generation in hemodialysis patients ( 1 ) , it may be a powerful determinant for anorexia , hypoalbuminemia , and the diagnosis of malnutrition in renal failure patients ( 1 , 3 , 21 ) . ( 3 ) reported that the mean crp levels in hd patients was higher than the upper limit of normal , while some patients with high leptin levels had low crp . although inflammatory marker levels are clearly increased in hd patients , this may be related to the exposure of blood to bioincompatible dialysis membranes ( 17 ) . other causes , including dietary and behavioral factors , cardiovascular diseases ( 29 ) , and high serum leptin levels ( 10 , 12 ) are also associated with an increase in crp levels . in recent years , the association between inflammation and serum leptin levels in dialysis patients has been established . some studies have reported that inflammatory process may contribute to the stimulation of leptin mrna , which leads to an increase in the circulating leptin levels ( 10 , 12 ) . the findings of the present study demonstrated that although the patients with elevated crp levels had markedly increased leptin concentration compared to patients with normal crp , this was similar to control subjects ( data not shown ) . however , no correlation was found between serum levels of crp with leptin and other nutritional factors , suggesting that crp is a poor predictor of malnutrition in dialysis patients . the limitations of our study included the small sample size and lack of longitudinal data . the findings suggest that low levels of leptin may contribute to malnutrition in hd patients . further studies are required in order to ascertain the significance of leptin in relation to nutritional factors in hemodialysis patients .