Inappropriate elevation of serum leptin levels in children with chronic renal failure

Decreased spontaneous nutrient intake is a frequent clinical problem in patients with chronic renal failure (CRF). Leptin, the recently characterized gene product of the obese gene, is produced by adipocytes and is thought to act as an afferent satiety signal on the appetite and satiety centers of the brain. Serum leptin levels were investigated in 134 pediatric patients in different stages of CRF to evaluate a possible relationship between leptin, GFR, and spontaneous energy intake. Serum leptin levels, measured by a specific RIA, were elevated above the 50th percentile of the normal range in 78% of CRF patients and above the 95th percentile in 45% of patients. Gel chromatography of CRF sera yielded only one single immunoreactive peak at 16 kD, indicating that the increase of immunoreactive leptin levels in CRF serum was not due to accumulation of leptin degradation products. Multiple stepwise regression analysis revealed the percentage of body fat as assessed from skinfold measurements (r = 0.79, P < 0.0001) and GFR (r = -0.17, P < 0.005) as independent predictors of serum leptin levels, accounting for 66% of total statistical variability. There was an inverse linear correlation between standardized leptin levels (leptin z-score) and the spontaneous energy intake quantified from written dietary diaries (r = -0.36, P < 0.001). These data suggest that the percentage of body fat remains the main determinant of serum leptin in CRF patients, but their levels increase with declining GFR, presumably by reduced renal clearance. Leptin levels in CRF serum that are inappropriately elevated in relation to the percentage of body fat might lead to a dysregulation of the normal peripheral-central leptin feedback loop, thereby contributing to decreased nutrient intake in uremia.