Anorexia and protein malnutrition, occasionally associated with obesity, are frequently observed in peritoneal dialysis (PD) patients. Both are recognized risk factors for cardiovascular (CV) morbidity and mortality. Leptin is produced by adipocytes and regulates body-fat mass through a satiety central effect. Leptin accumulates in the uremic state. We analyzed the relationship between plasma leptin levels, nutritional status, obesity, CV risk factors, and atherosclerosis in PD patients. Leptin was determined using a polyclonal antibody [radioimmunoassay: Linco Research, St. Louis, MO, U.S.A.]. The normal range was 1-7.8 ng/mL. We studied 38 PD patients. Mean leptin levels were 59.1 +/- 57.5 ng/mL (elevated in 32 patients). Women (n = 21) showed higher leptin levels than did men (80.4 +/- 60 ng/mL vs. 32.3 +/- 43.3 ng/mL, p < 0.01), in spite of both groups having a similar body mass index (BMI). A statistically significant direct correlation was found between leptin and BMI (r = 0.7, p < 0.01) and triceps skin-fold measurement (r = 0.77, p < 0.01). Leptin levels and renal creatinine clearance (CCr) showed no significant correlation. Independent of BMI, higher leptin levels were associated with parameters considered to be CV risk factors (Framingham study), such as serum triglycerides < 150 mg/dL (n = 29) as compared with > 150 mg/dL (44.2 +/- 53.2 ng/mL vs. 80 +/- 58.4 ng/mL, p < 0.05), cholesterol < 250 mg/dL (n = 28) as compared with > 250 mg/dL, (50 +/- 55.6 mg/dL vs. 84.7 +/- 57.7 mg/dL, p < 0.05), uric acid < 7 mg/dL (n = 28) as compared with > 7 mg/dL (47 +/- 53.7 mg/dL vs. 93.1 +/- 56.6 mg/dL, p < 0.05), and the presence or lack of presence of left ventricular hypertrophy [68.8 +/- 60 (n = 30) vs. 29.5 +/- 23.7 (n = 5), p < 0.05]. The patients were classified into two groups according to a clinical atherosclerosis score (CAS). Nineteen patients had low CAS scores, and they showed higher plasma leptin values than did the other patients (82.4 +/- 65.7 ng/mL vs 35.8 +/- 36.6 ng/mL, p < 0.05). Twelve patients with anorexia had lower leptin values than did patients with normal appetite (19.2 +/- 15.8 ng/mL vs. 91.3 +/- 58.8 ng/mL, p < 0.001). In non obese patients (BMI < 25 and CCr < 3 mL/min, n = 14), leptin had a statistically significant direct linear correlation with markers of nutrition, including albumin (r = 0.63, p < 0.05), transferrin (r = 0.4, p < 0.05), cholesterol (r = 0.65, p < 0.05), and triglycerides (r = 0.6, p < 0.05). Finally, plasma leptin levels were notably increased in the PD population, indicating increased production (possibly by chronic hyperinsulinism), or uremic retention, or both. By multivariate analysis, we confirmed the association between leptin levels and sex, leptin and BMI, and leptin levels > 40 ng/mL and sex and LVH. All of those features suggest that plasma leptin levels could be considered a marker of CV risk and food intake in non obese PD patients without inflammation.