Role of the kidney in human leptin metabolism.

To assess the role of the human kidney in leptin metabolism, we measured renal leptin net balance and urinary leptin excretion in 16 normal postabsorptive volunteers with varying degrees of obesity. Arterial leptin concentrations (11.6 +/- 2.7 ng/ml) significantly exceeded renal vein concentrations (10.3 +/- 2.5 ng/ml, P < 0.001). Renal leptin fractional extraction averaged 13.1 +/- 1.1%, and renal leptin net balance (uptake) averaged 1,070 +/- 253 ng/min. Lineweaver-Burk analysis indicated that renal leptin uptake followed saturation kinetics with an apparent Michaelis-Menten constant of 10.9 ng/ml and maximal velocity of 1,730 ng/min. Leptin was generally undetectable in urine. Using literature values for systemic leptin clearance, we calculated that renal leptin uptake could account for approximately 80% of all leptin removal from plasma. These data indicate that the human kidney plays a substantial role in leptin removal from plasma by taking up and degrading the peptide.