Leptin--a new hormone of definite interest for the nephrologist.

and poor nutrition in patients with renal failure [7]. Introduction Since protein binding may be enhanced by renal failure, it could be argued that the elevated serum leptin The obesity (ob) gene protein, known as leptin (from demonstrated in the present study are due to an excess Greek leptos ‘thin’), was cloned in 1994 by Friedman of bound forms of leptin rather than free bioactive et al. [1] and regulates food intake and energy expenditforms. However, a recent study has shown that elevated ure in animal models. Leptin which is exclusively leptin in patients with CRF are due to an increase in produced in the adipocytes, circulates in the blood the free bioactive form of leptin rather than in bound with ~50% in free form and the remainder attached forms [4]. to binding proteins. Leptin reaches the brain by a saturable transport mechanism via the blood–brain barrier and, via direct effects on the hypothalamus, Causes of hyperleptinaemia in chronic renal failure decreases appetite and increases metabolism. Markedly elevated leptin levels have been reported in patients As the kidneys are important in clearing several other with obesity, who seem to be insensitive to the endogenpolypeptide hormones such as insulin, parathyroid ous leptin production. It has been proposed that in hormone, and glucagon, it seems reasonable to surmise obese patients there is a defective transport of leptin that leptin also accumulates in the case of renal failure across the blood–brain barrier indicating a resistance due to reduced renal clearance. However, elevated to the central actions of leptin. Treatment with recomserum leptin are not a universal finding in advanced binant leptin induces dramatic 40% weight reduction CRF [8], and the exact cause of elevated serum leptin in mice [2], but no results are as yet available regarding in uraemia is not well understood, although there are the weight-reducing effect of recombinant leptin treatdata suggesting that a decrease in glomerular filtration ment on obese humans. rate [4,6,9, P. Stenvinkel, unpublished data], inflammation [3] and hyperinsulinaemia [8,10] may affect serum leptin levels in CRF. Leptin, insulin concentrations, and body weight, are interrelated and there is a Leptin in chronic renal failure direct correlation between insulin and leptin concentrations in non-uraemic [11] as well as uraemic patients Protein–calorie malnutrition is a common problem in [8,10]. It has been shown that long-term (72 h) insulin patients with advanced chronic renal failure (CRF) infusion stimulates leptin secretion in humans [12]. and is associated with increased morbidity and mortalAnother possible reason for elevated leptin levels in ity. Numerous factors contribute to malnutrition, but renal failure is chronic inflammation [3]. It has been reduced food intake due to anorexia is probably the demonstrated that cytokines, such as TNFa and IL-1, most important. The mechanism(s) causing decreased induce both an increase in leptin mRNA concentraappetite in uraemia are not obvious. However, in 1997 tions and anorexia in animals [13], and this suggests a number of studies demonstrated that CRF patients that elevated leptin concentrations may be one of the with [3–6 ] and without [3,6,7] ongoing dialysis treatmechanisms by which anorexia is induced during ment have markedly elevated serum leptin without an inflammatory conditions. increase in body fat mass. Since leptin is thought to be an inhibitor of appetite, by restraining the synthesis and release of neuropeptide Y, it has been speculated Consequences of hyperleptinaemia in chronic renal that elevated serum leptin could contribute to anorexia failure