| Abstract|| |
To evaluate the relationship between hyperleptinemia and anemia in hemodialysis patients, we investigated the reverse epidemiological role of leptin in 36 patients (males: 21, diabetics: 11) under regular chronic hemodialysis. The patients had complete blood counts, iron profile, serum leptin, and adequacy of hemodialysis measured. We found a significant positive correlation of serum leptin with hemoglobin level and body mass index (BMI). A trend between serum leptin and total iron binding capacity was observed, however, no correlation was observed with serum ferritin. No differences in these correlations were observed in any subgroup related to gender or diabetes. Our data support previous findings showing that greater serum leptin levels are associated with greater hemoglobin levels.
Keywords: Leptin, Anemia, Hemodialysis, Hemoglobin.
|How to cite this article:|
Nasri H. Association of Serum Leptin with Anemia in Maintenance Hemodialysis Patients. Saudi J Kidney Dis Transpl 2006;17:521-5
|How to cite this URL:|
Nasri H. Association of Serum Leptin with Anemia in Maintenance Hemodialysis Patients. Saudi J Kidney Dis Transpl [serial online] 2006 [cited 2021 Jul 25];17:521-5. Available from: https://www.sjkdt.org/text.asp?2006/17/4/521/32490
| Introduction|| |
Leptin, an adipose tissue cytokine, is a small peptide hormone that is mainly but not exclusively, produced in adipose tissue.  Leptin exerts several important metabolic effects on peripheral tissue, including the modification of insulin action, induction of angiogenesis, and modulation of the immune system. ,,
Several recent studies have demonstrated that leptin is cleared principally by the kidney. Therefore, serum leptin concentrations are increased in patients with chronic renal failure and those undergoing maintenance dialysis.  It has been speculated that hyperleptinemia may contribute to uremic anorexia and malnutrition. ,
In the general population, leptin is considered an "appetite inhibitor". However, in contrast to preliminary studies, its role in chronic kidney disease (CKD) and hemodialysis (HD) patients is not completely understood. Although serum leptin is generally elevated in CKD and HD patients, some studies were unable to demonstrate that leptin is a cause of uremia-related anorexia.  More recent studies in maintenance dialysis patients suggest a paradoxically inverse association between elevated serum leptin and markers of nutritional status, , a finding that is consistent with the theory of reverse epidemiology. 
Usually CKD patients develop anemia, which predominantly results from insufficient erythropoietin production by the diseased kidneys.  During hematopoiesis, there are many growth factors, which stimulate the proliferation and maturation of the erythroid progenitors. The main one is erythropoietin, which acts in concert with other growth factors. Recently, it was suggested that leptin could be involved in an early stage of erythropoiesis and leptin has been demonstrated to stimulate hematopoietic stem cells in vitro. , Data regarding the association of serum leptin to anemia in regular hemodialysis patients are quiet scarce.
The purpose of the present prospective study was to determine whether hyperleptinemia correlated with anemia markers in diabetic and non-diabetic hemodialysis patients.
| Patients and Methods|| |
This cross-sectional study was conducted on chronic hemodialysis patients. The patients were maintained on acetate based dialysate and polysulfone dialyzers. Most of the patients were on oral active 1-25 vitamin D3, calcium carbonate, sevelamer, intravenous iron sucrose, L-carnitine (500mg daily), oral Vitamin Bcomplex, and recombinant human erythropoietin (rHuEPO) 2000 IU/ HD session. We excluded patients who had active or chronic infection, and those using non-steroidal anti-inflammatory drugs (NSAID) or angiotensin converting enzyme (ACE) inhibitors.
The investigations on the study patients included complete blood counts, serum iron, total iron binding capacity (TIBC), serum ferritin, serum creatinine, pre and post-dialysis blood urea nitrogen (BUN). Blood samples were drawn after an overnight fast. Serum Leptin (normal range of values for males is 3.84 (±1.79) and for females is 7.36 (±3.73) ng/ml) was measured by enzyme-linked immunosorbent assay (ELISA) method using DRG kits- Germany.
To determine the efficacy of hemodialysis, the urea reduction rate (URR) was calculated from pre- and post-blood urea nitrogen (BUN) data.  Body mass index (BMI) was calculated using the standard formula (post dialysis weight in kilograms/height in square meters; kg/m 2 ).  Duration and sessions of hemodialysis treat-ment were obtained from the patients' records. The duration of each hemodialysis session was 4 hours.
| Statistical Analysis|| |
Statistical analysis was performed on total hemodialysis (HD), females, males, diabetic and non-diabetic populations separately. Data were expressed as the mean ± standard deviation (SD). Student's t-test was used to compare the study groups. Partial correlation and Pearson tests were used to evaluate statistical correlations. All statistical analyses were performed using SPSS (version 11.5.00). Statistical significance was determined at a p-value <0.05.
| Results|| |
We studied 36 HD patients (15 females, 21 males) consisting of 25 (11 females, 14 males) non-diabetic patients and 11 (4 females, 7 males) diabetic HD patients.
[Table - 1] shows the patients' data. The mean patients' age was 47 ± 17 years. The median value of serum leptin in the study patients was 5.75 ng/ml; the median values of serum leptin in the diabetic and non-diabetic groups were 8.3 and 4 ng/ml, respectively.
There was a significant positive correlation of serum leptin with hemoglobin levels (r = 0.36, p =0.033, [Figure - 1]). We also found a significant positive correlation of serum leptin with BMI (r = 0.56, p <0.001, [Figure - 2]). There was no significant correlation between serum leptin and serum ferritin or TIBC in all patients or in the subgroups.
| Discussion|| |
In this study, we found a significant positive correlation between serum leptin and hemoglobin and BMI. Tungtrongchitr et al studied 214 overweight patients without renal failure (BMI ≥25) and found that there were significantly higher serum leptin levels, mean corpuscular hemoglobin concentration and mean corpuscular volume in the overweight relative to the control subjects. Significant associations were observed between weight, height, BMI, hemoglobin, and serum leptin in both males and females.  Moreover, three longitudinal/observational studies in HD patients indicated that individuals with high serum leptin levels were more likely to lose weight. ,, However, recent studies of hemodialysis patients suggest a paradoxically inverse association between higher serum leptin and markers of nutritional status,, a finding that was consistent with the theory of reverse epide-miology. Leptin is similar to serum albumin, which is a negative acute phase reactant in end-stage renal failure patients.
A study conducted by Dedoussis et al. on 40 beta-thalassemia patients found that leptin might play some role in hematopoiesis. Kokot et al assessed the influence of 12 months of rHuEPO therapy on plasma leptin in 15 HD patients and showed significantly lower leptin level after 3, 6, and 12 months of rHuEPO therapy as compared to the beginning of the study. 
Of interest, hemodialysis (HD) patients with a high body mass index (BMI) are less likely to experience severe anemia. , In this regard, Takeda et al evaluated patients who could maintain high hemoglobin levels without the use of rHuEPO and found that in long-term HD patients, serum leptin levels correlated inversely with rHuEPO dose.  Stenvinkel et al. also observed that weekly rHuEPO doses correlated negatively with both body fat mass and serum leptin levels in patients with ESRD not yet receiving dialysis.  Hung et al. hypothesized that increasing caloric intake, body fat mass and leptin levels may enhance erythropoiesis in long-term HD patients; hyperleptinemia may reflect better nutritional status and rHuEPO response in HD patients. Increasing energy intake improves erythropoiesis, which may be partly mediated by an increase in serum leptin levels.  Increased leptin levels could both enhance the erythropoietic response and reduce rHuEPO dose when greater body fat mass is achieved by caloric supplementation. 
Finally, although leptin is considered an "appetite inhibitor" in the general population, its role in ESRD patients is somewhat unconventional. Serum leptin is generally elevated in ESRD patients, but this has not been observed in anorexia. Leptin has been shown to act synergistically with EPO to stimulate end-stage colony-forming-unit erythroid in humans. 
In conclusion, we observed a positive correlation between serum leptin levels and BMI and hemoglobin, which supports the theory of a reverse epidemiological role for leptin in the maintenance of hemodialysis patients.
| References|| |
|1.||Zoccali C, Panuccio V, Tripepi G, Cutrupi S, Pizzini P, Mallamaci F. Leptin and biochemical markers of bone turnover in dialysis patients. J Nephrol 2004;17:253-60. [PUBMED] [FULLTEXT]|
|2.||Wolf G, Chen S, Han DC, Ziyadeh FN.Leptin and renal disease. Am J Kidney Dis 2002;39(1):1-11. |
|3.||Stamatiadis DN, Chan JL, Cogswell R, et al.Elevated leptin fragments in renal failure correlate with BMI and haematopoiesis and are normalized by haemodialysis. Clin Endocrinol (Oxf) 2004;60(4):434-41. |
|4.||Stenvinkel P. Leptin and Its Clinical Implications in Chronic Renal Failure. Miner Electrolyte Metab 1999;25:298-302. [PUBMED] |
|5.||Nakazono H, NagakeY, Ichikawa H, et al. Serum Leptin Concentrations in Patients on Hemodialysis. Nephron 1998;80:35-40. |
|6.||Pecoits-Filho R, Lindholm B, Stenvinkel P. End-stage renal disease: a state of chronic inflammation and hyperleptinemia. Eur J Clin Invest 2003;33:527-8. [PUBMED] [FULLTEXT]|
|7.||Don BR, Rosales LM, Levine NW, Mitch W, Kaysen GA. Leptin is a negative acute phase protein in chronic hemodialysis patients. Kidney Int 2001;59:1114-20. [PUBMED] [FULLTEXT]|
|8.||Kalantar-Zadeh K, Block G, Humphreys MH, Kopple JD. Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients. Kidney Int 2003;63:793808. [PUBMED] [FULLTEXT]|
|9.||Fisher JW. Mechanism of the anemia of chronic renal failure. Nephron 1980;25:106111. [PUBMED] |
|10.||Majdan M, Kotarski J, Ksiazek A.Evaluation of the relationship between possible control of anemia in hemodialysis patients and the concentration of leptin. Pol Arch Med Wewn 1999;101(4):295-300. |
|11.||Markova M, Haluzik M, Svobodova J, Rosicka M, Nedvidkova J, Haas T. Serum leptin levels in patients with sideropenic and pernicious anemia: the influence of anemia treatment. Physiol Res 2000;49(6): 679-84. |
|12.||Boag JT. Basic truths in optimal hemodialysis. Dial Transplant 1994;23:636. |
|14.||Tungtrongchitr R, Pongpaew P, Phonrat B, et al. Leptin concentration in relation to body mass index (BMI) and hematological measurements in Thai obese and overweight subjects. Southeast Asian J Trop Med Public Health 2000;31(4):787-94. |
|15.||Stenvinkel P, Lindholm B, Lonnqvist F, Katzarski K, Heimburger O. Increases in serum leptin levels during peritoneal dialysis are associated with inflammation and a decrease in lean body mass. J Am Soc Nephrol 2000;11:1303-9. [PUBMED] [FULLTEXT]|
|16.||Odamaki M, Furuya R, Yoneyama T, et al. Association of the serum leptin concentration with weight loss in chronic hemodialysis patients. Am J Kidney Dis 1999;33:361-8. [PUBMED] |
|17.||Heimburger O, Lonnqvist F, Danielsson A, Nordenstrom J, Stenvinkel P. Serum immunoreactive leptin concentration and its relation to the body fat content in chronic renal failure. J Am Soc Nephrol 1997;8: 1423-30. [PUBMED] |
|18.||Dedoussis GV, Kyrtsonis MC, Andrikopoulos NE, Voskaridou E, Loutradis A.Inverse correlation of plasma leptin and soluble transferrin receptor levels in beta-thalassemia patients. Ann Hematol 2002;81(9):543-7. |
|19.||Kokot F, Wiecek A, Mesjasz J, Adamczak M, Spiechowicz U.Influence of long-term recombinant human erythropoietin (rHuEpo) therapy on plasma leptin and neuropeptide Y concentration in haemodialysed uraemic patients. Nephrol Dial Transplant 1998; 13(5):1200-5. |
|20.||Locatelli F, Aljama P, Barany P. Revised European Best Practice Guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant 2004;19:S29-S30. (suppl 2). |
|21.||Kalantar-Zadeh K, McAllister CJ, Lehn RS, Lee GH, Nissenson AR, Kopple JD. Effect of malnutrition-inflammation complex syndrome on EPO hyporesponsiveness in maintenance hemodialysis patients. Am J Kidney Dis 2003;42:761-73. [PUBMED] [FULLTEXT]|
|22.||Takeda A, Toda T, Shinohara S, Mogi Y, Matsui N. Factors contributing to higher hematocrit levels in hemodialysis patients not receiving recombinant human erythropoietin. Am J Kidney Dis 2002;40:104-9. [PUBMED] [FULLTEXT]|
|23.||Stenvinkel P, Heimburger O, Lonnqvist F, Barany P. Does the ob gene product leptin stimulate erythropoiesis in patients with chronic renal failure? Kidney Int 1998; 53:1430-1. [PUBMED] [FULLTEXT]|
|24.||Hung SC, Tung TY, Yang CS, Tarng DC. High-calorie supplementation increases serum leptin levels and improves response to rHuEPO in long-term hemodialysis patients. Am J Kidney Dis 2005;45:1073-83. [PUBMED] [FULLTEXT]|
|25.||Mikhail AA, Beck EX, Shafer A. Leptin stimulates fetal and adult erythroid and myeloid development. Blood 1997;89:1507-12. |
Internist, Nephrologist, Associate Professor, Department of internal medicine, Shahrekord University of Medical Sciences, Shahrekord
[Figure - 1], [Figure - 2]
[Table - 1]