INCREASED PLASMA LEPTIN CONCENTRATION IN END-STAGE RENAL-DISEASE

Leptin is a 16-kDa protein recently identified as the obese gene produ ct involved in body weight regulation. Administration of recombinant l eptin to ob/ob mice, which have a genetic defect in leptin production, reduces food intake and increases energy expenditure. Leptin is synth esized by fat cells, and in normal humans, plasma concentrations are p roportional to adiposity. The physiological actions and the degradatio n pathways of leptin in humans are unknown. We investigated renal elim ination of leptin by comparing plasma leptin concentrations in end-sta ge renal disease (ESRD) patients with normal controls. Our hypothesis was that if renal filtration is a significant route of elimination, th e hormone would accumulate in ESRD patients. Mean plasma levels in 141 ESRD patients (26.8 +/- 5.7 and 38.3 +/- 5.6 mu g/L for males and fem ales, respectively) were significantly higher (P < 0.001) than mean va lues obtained in normal controls (11.9 +/- 3.1 and 21.2 +/- 3.0 mu g/L for males and females, respectively). Leptin concentrations in ESRD p atients correlated directly with body mass index (BMI; r = 0.77 for me n and 0.78 for women). The rate of increase in leptin concentrations w ith BMI was significantly greater in ESRD patients (5.5 and 6.6 mu g/L /U BMI for men and women, respectively) than in normal controls (1.4 a nd 2.6 mu g/L/U for men and women, respectively). Pre- and postdialysi s leptin levels in hemodialysis patients were similar. Western blot of plasma hom ESRD patients with high leptin levels showed bands corresp onding to the intact protein (16 kDa) with no lesser or greater molecu lar mass species observed. Leptin concentrations in patients with ESRD did not correlate with measures of residual renal function (serum cre atinine, beta(2)-microglobulin, PTH, or GH levels). Similarly, we foun d no correlation between leptin levels and the number of years patient s had been on dialysis or with recent weight changes. We conclude that intact leptin is increased in ESRD patients, but does not appear to c ause decreased weight. As leptin levels did not correlate with residua l renal function, increased production may account for the high levels observed.