Peritoneal clearance of leptin in CAPD patients: impact of local insulin administration

The ob gene product leptin is secreted by fat cells and the serum leptin levels reflects the body fat content. Markedly elevated serum leptin levels have been reported in patients with chronic renal failure. The aim of the present study was to assess if the dialysate leptin levels in peritoneal dialysate are similar to what can be expected from passive diffusion or if intraperitoneal synthesis of leptin may occur.

We studied 39 patients (20 males), mean age 54+/-12 years, who had been treated with peritoneal dialysis for 17+/-12 months. Ten of the patients were diabetics of which seven used intraperitoneal insulin. A 24-h collection of dialysate was performed and dialysate and fasting blood samples were analysed for leptin, albumin and beta2-microglobulin, and the peritoneal clearances (PCl) were calculated for these solutes.

Serum leptin (mean 47+/-76, range 3-350 ng/ml) was related to body mass index (r=0.35, P<0.05). In multiple regression analysis, serum leptin also correlated to serum TNF-alpha. Although dialysate leptin levels correlated to serum leptin, they were higher than expected from the molecular weight of 16 kD. PCl of leptin was 1.3 ml/min (range 0.2-5.9 ml/min), which was 1.6 times higher than expected from the molecular weight of leptin and PCl for albumin and beta2-microglobulin, not taking the protein binding of leptin into account. A strong correlation was found between PCI for albumin and beta2-microglobulin (r = 0.68, P < 0.0001) but neither PCl albumin, nor PCl beta2-microglobulin correlated to PCI leptin. The PCl of leptin was markedly higher in diabetics using intraperitoneal insulin (n = 7) compared to the other 32 patients (2.6+/-2.0 vs 1.1+/-0.7 ml/min, P<0.05).

Serum leptin is locally produced in the peritoneal cavity, and intraperitoneal insulin enhances local production of leptin.