Leptin, secreted from fat cells, functions as a lipostat mechanism through modulation of satiety signals. Markedly elevated leptin levels have been documented in uremic patients, especially in those who are treated by peritoneal dialysis (PD). However, the role of hyperleptinemia in uremic patients is not clear, and it is not known whether elevated leptin levels contribute to uremic anorexia and changes in body composition. In this prospective study, serum leptin, C-reactive protein (CRP), plasma insulin, and body composition (dual-energy x-ray absorptiometry) were measured in 36 patients (53 +/- 1 yr) close to start and after about 1 yr of PD. In addition, markers of dialysis adequacy and urea kinetics were followed during treatment with PD. During PD, the total body fat mass (20.5 +/- 1.0 to 22.9 +/- 1.3 kg; P < 0.01), truncal fat mass (11.5 +/- 0.7 to 13. 2 +/- 0.9 kg; P < 0.001), and serum leptin levels (20.1 +/- 3.8 to 35.6 +/- 6.8 ng/ml; P < 0.01) increased markedly, especially in patients with diabetes mellitus. Twenty-five PD patients that lost lean body mass during PD had significantly (P < 0.05) elevated initial CRP levels (14 +/- 2 mg/L) compared to 11 patients (<10 mg/L) who gained lean body mass during PD. A significant increase in serum leptin levels (20.9 +/- 4.2 to 42.7 +/- 4.0 ng/ml; P < 0.001) was observed in those patients who lost lean body mass, whereas no such change (18.4 +/- 8.4 to 19.2 +/- 6.4 ng/ml) was observed in the patients that gained lean body mass during PD treatment. The present longitudinal results demonstrate that serum leptin level and body fat content increase markedly during PD, especially in diabetic patients. Patients that lost lean body mass during PD had higher initial CRP levels and increased their serum leptin levels significantly during PD compared to those patients that gained lean body mass. Additional studies are therefore needed to elucidate the role of hyperleptinemia and inflammation in causing anorexia, protein-malnutrition, and changes in body composition during treatment with PD.