Leptin and end-stage renal disease
- Lynda Szczech, MD, MSCE
Lynda Szczech, MD, MSCE
- Durham Nephrology Associates, Durham, NC
- Jula K Inrig, MD, MHSc
Jula K Inrig, MD, MHSc
- Adjunct Associate in Medicine, Duke University
- Associate Clinical Professor, University of California Irvine
Leptin is the 16,000 dalton protein product of the obesity gene (ob), which is mainly produced by adipocytes . In animal models, it is a potent anorectic and regulates energy expenditure [2-4] and may be similarly involved in body weight maintenance in humans.
Leptin is released into the bloodstream, where it binds to leptin-binding proteins and is transported into the cerebrospinal fluid by receptors in the choroid plexus via a saturable transport mechanism . It exerts its major effect on the hypothalamus, where a Janus kinase signal transducer and activator of transcription (Jak/STAT) signal cascade is activated. This decreases production of neuropeptide Y (NPY), an extremely potent appetite stimulant, thereby resulting in suppressed appetite, increased energy expenditure, and weight loss . In addition, leptin suppresses alpha-melanocyte-stimulating hormone, a compound that also blocks feelings of hunger.
Investigators have therefore postulated that leptin may be related to the anorexia and protein energy wasting frequently observed in patients with end-stage renal disease (ESRD). A review of leptin in patients with chronic kidney disease (CKD) is presented here. Detailed discussions relating to the physiology of leptin and the pathogenesis of obesity are presented separately. (See "Physiology of leptin" and "Genetic contribution and pathophysiology of obesity".)
Obesity gene (Ob)/ob mice have genetic traits that result in marked obesity, hyperphagia, glucose intolerance, insulin resistance, low energy expenditure, and sterility. When these mice are exposed to circulating factors from normal mice, they reduce food intake and experience weight loss. Via a positional cloning approach, this factor was isolated and subsequently named leptin, from the Greek word leptos, meaning "thin" . When recombinant leptin is exogenously administered to ob/ob mice, food intake is reduced and physical activity is enhanced, leading to weight loss [2-4].
A distinct obese strain of mice that is phenotypically identical to the ob/ob mouse is the db/db mouse. These mice have a mutation in the leptin receptor, with hyperleptinemia due to receptor resistance.
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- PHYSIOLOGIC EFFECTS
- LEPTIN REMOVAL BY THE KIDNEY
- HYPERLEPTINEMIA IN CHRONIC KIDNEY DISEASE
- Loss of renal function
- Hemodialysis membranes and dialysis modality
- Low erythropoietin levels
- Chronic inflammation
- Hyperinsulinemia and insulin resistance
- HYPERLEPTINEMIA IN RENAL TRANSPLANT
- CLINICAL SIGNIFICANCE OF HYPERLEPTINEMIA IN END-STAGE RENAL DISEASE
- SUMMARY AND RECOMMENDATIONS