Elevated leptin fragments in renal failure correlate with BMI and haematopoiesis and are normalized by haemodialysis.
OBJECTIVE
Leptin is an adipocyte hormone important in appetite, energy homeostasis, neuroendocrine and haematopoietic function. Patients with renal failure often have elevated total and free leptin levels. Biologically active leptin fragments (leptin(22-56) and leptin(57-92)) have been identified, but whether these fragments are affected by renal failure and/or haemodialysis (HD) is not known.


METHODS
Leptin, leptin(22-56) and leptin(57-92) levels were measured in 28 HD patients [14 men, 14 women, age 45.5 +/- 16.4 years, body mass index (BMI) 23.8 +/- 3.6 kg/m2] and 25 healthy controls with similar age and BMI. In 18 HD patients, leptin and fragment levels were measured before and after 2 consecutive dialysis treatments and on the intermediate, dialysis-free day.


RESULTS
Baseline leptin levels were higher in HD patients vs. controls (69.3 +/- 62.2 ng/ml vs. 30.4 +/- 32.7, P < 0.02) as were leptin(22-56) (7.14 +/- 7.04 ng/ml vs. 1.86 +/- 1.84, P < 0.02) and leptin(57-92) (5.94 +/- 6.08 ng/ml vs. 1.58 +/- 1.98, P < 0.02). Baseline leptin and fragment levels correlated significantly and independently with BMI in HD patients (r = 0.70, r = 0.59, r = 0.72, respectively, P < 0.001). After each HD session, leptin levels were reduced to levels not different from controls, but increased on the intermediate, dialysis-free day. Similar to and independently from total leptin, both leptin fragments were reduced after the first HD session to levels not different from controls. The reduction in leptin levels was higher with synthetic vs. cellulosic membrane types (37.7 +/- 23.5%vs. 18.1 +/- 21.8%, P < 0.03). Leptin correlated weakly with the erythropoietin to haematocrit ratio (T = -0.20, P = 0.14), while leptin(22-56) had a significant negative correlation with this index (T = -0.42, P < 0.01), suggesting that this fragment may favour haematopoiesis.


CONCLUSIONS
Leptin fragments are detected in human serum, and both leptin and leptin fragments correlate with BMI, are significantly elevated in HD patients compared to controls, and are significantly decreased by haemodialysis. The elevated leptin fragments may have important physiological significance for the anorexia, hypogonadism, and anaemia commonly seen in HD patients, but this remains to be conclusively shown by interventional trials.
Stamatiadis
Dimitrios N
DN
Division of Nephrology, Department of Internal Medicine, Laiko Hospital, University of Athens School of Medicine, Athens, Greece.
Chan
Jean L
JL
Cogswell
Rebecca
R
Stefanopoulou
Helen C
HC
Bullen
John
J
Katsilambros
Nicholas
N
Stathakis
Charalambos P
CP
Mantzoros
Christos S
CS
D000328:Adult; D000704:Analysis of Variance; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D006410:Hematopoiesis; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011233:Precipitin Tests; D006435:Renal Dialysis
D020738:Leptin; D010446:Peptide Fragments; C487163:leptin 22-56; C487164:leptin 57-92