Role of the kidney in removing circulating leptin in humans

ABSTRACT

To assess the role of the kidney in removing circulating leptin in humans by studying the leptin metabolism across the renal bed of normal human kidney and also studying the circulating leptin levels in end stage renal disease [ESRD] patients maintained on hemodialysis [HD]. The study included 14 human subjects with intact renal functions and who were scheduled for elective cardiac catheterization. Aortic, renal vein, peripherial arterial and urine samples were withdrawn from each subject. A separate cohort of 32 patients with ESRD maintained on HD were also included in the study. A blood sample was taken from the arterial limb of the vascular access of each patient before and after the HD session. For all samples, leptin levels were determined by radioimmunoassay [RIA]. In subjects with intact renal functions, plasma leptin concentrations were significantly increased in the aorta than in the renal vein [11.3 +/- 3.1 vs. 10.1 +/- 2.9 ng/ml] indicating net renal leptin uptake [RU]. The calculated RU was 849 +/- 184 ng/min which accounted for 65% of all leptin removed from the circulation. The calculated renal leptin fractional extraction [Fx] was 15.6 +/- 2%. Lineweaver-Burk analysis indicated that RU followed saturation kinetics with an apparent Michaelis-Menten constant of 10.7ng/ml and maximal velocity of 1700 ng/min. Leptin was generally undetectable in urine. In ESRD patients on HD, the peripheral arterial leptin levels standardized for body mass index were increased by fourfold as compared to control subjects with intact renal function. In addition, plasma leptin is not cleared by hemodialysis with a modified cellulose membrane. Human kidney plays a substantial role in leptin removal from the circulation by taking up and degrading the peptide. ESRD patients have higher levels of circulating leptin which are not cleared by hemodialysis using modified cellulose membrane