MECHANISM OF LEPTIN REMOVAL FROM THE CIRCULATION BY THE KIDNEY

This study was performed to test the hypothesis that the kidneys play a primary role in the clearance of endogenous leptin from the circulat ion. Lean male Sprague-Dawley rats were anesthetized and subjected to various surgical manipulations of the kidneys. Sixty minutes after sur gery arterial blood samples were taken at 1-h intervals for up to 8 h. Plasma leptin levels were determined by radioimmunoassay. Bilateral n ephrectomy induced a rapid increase in plasma leptin concentrations ab ove control values, indicating that the kidneys are important for the elimination of leptin from the circulation. Leptin was not metabolized across the renal circulation and was extracted intact by the kidney. Simultaneous measurement of renal plasma flow established renal leptin extraction at approximately 6.5 ng/min for both kidneys. Compared wit h the quantities extracted from the plasma, leptin was only present in the urine in small quantities, indicating extensive metabolic degrada tion in the renal tubules. High plasma leptin levels were not maintain ed after binephrectomy indicating that pathways other than the kidneys are also responsible for leptin clearance. Seven hours after bilatera l ureteral ligation, procedure which lowers glomerular filtration, pla sma leptin levels were slightly elevated. The renal extraction of lept in did not change over a wide range of plasma leptin concentrations su ggesting that renal leptin extraction is a high capacity, non-saturabl e process most probably glomerular filtration. Endogenous leptin is ra pidly cleared from the circulation by glomerular filtration followed b y metabolic degradation in the renal tubules.