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Orexigenic and anorexigenic mechanisms in the control of nutrition in chronic kidney disease.
Pediatr Nephrol. 2005 Mar; 20(3):427-31.PN

Abstract

Malnutrition is defined as abnormalities caused by an inadequate diet, but this term is often used inappropriately to describe the syndrome of loss of body weight with muscle mass being replaced by fatty tissue and declining serum proteins present in adults and children with chronic kidney disease (CKD). This syndrome is more accurately described as cachexia, and manifests as growth failure in children with CKD. Cachexia is common and is an important risk factor for poor quality of life and increased mortality and morbidity in both adults and children with CKD. Anorexia, acidosis and inflammation are important causes of cachexia, but the underlying molecular mechanism is not well understood. Dietary intake is often poor and resting metabolic rate is increased in CKD. The energy cost of growth is increased in experimental CKD. Circulating concentrations of cytokines, such as leptin, tumor necrosis factor-alpha and interleukins 1 and 6 are increased in patients with CKD and correlate with the degree of cachexia in these individuals. We hypothesize that cytokines signal through orexigenic neuropetides such as agouti-related peptide and neuropeptide Y (NPY), and anorexigenic neuropetides such as proopiomelanocortin and alpha-melanocyte-stimulating hormone in the arcuate nucleus in the hypothalamus. This signaling system also involves the NPY receptor and the melanocortin receptors and controls appetite and metabolic rate in health and disease. Furthermore, the first order neurons of this system are located outside the blood-brain barrier and can therefore sense the circulating levels of cytokines, as well as long-term satiety hormones such as leptin and insulin and short-term satiety hormones such as ghrelin and peptide (P) YY. There is experimental evidence that this hypothalamic neuropeptide signaling system may have an important role in the pathogenesis of cachexia in CKD. Understanding the molecular mechanism of cachexia in CKD may lead to novel therapeutic strategies.

Authors+Show Affiliations

Department of Pediatrics, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, NRC5, Portland, OR, 97239, USA. makr@ohsu.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

15662537

Citation

Mak, Robert H., et al. "Orexigenic and Anorexigenic Mechanisms in the Control of Nutrition in Chronic Kidney Disease." Pediatric Nephrology (Berlin, Germany), vol. 20, no. 3, 2005, pp. 427-31.
Mak RH, Cheung W, Cone RD, et al. Orexigenic and anorexigenic mechanisms in the control of nutrition in chronic kidney disease. Pediatr Nephrol. 2005;20(3):427-31.
Mak, R. H., Cheung, W., Cone, R. D., & Marks, D. L. (2005). Orexigenic and anorexigenic mechanisms in the control of nutrition in chronic kidney disease. Pediatric Nephrology (Berlin, Germany), 20(3), 427-31.
Mak RH, et al. Orexigenic and Anorexigenic Mechanisms in the Control of Nutrition in Chronic Kidney Disease. Pediatr Nephrol. 2005;20(3):427-31. PubMed PMID: 15662537.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Orexigenic and anorexigenic mechanisms in the control of nutrition in chronic kidney disease. AU - Mak,Robert H, AU - Cheung,Wai, AU - Cone,Roger D, AU - Marks,Daniel L, Y1 - 2005/01/21/ PY - 2004/04/03/received PY - 2004/11/09/accepted PY - 2004/11/08/revised PY - 2005/1/22/pubmed PY - 2005/10/19/medline PY - 2005/1/22/entrez SP - 427 EP - 31 JF - Pediatric nephrology (Berlin, Germany) JO - Pediatr Nephrol VL - 20 IS - 3 N2 - Malnutrition is defined as abnormalities caused by an inadequate diet, but this term is often used inappropriately to describe the syndrome of loss of body weight with muscle mass being replaced by fatty tissue and declining serum proteins present in adults and children with chronic kidney disease (CKD). This syndrome is more accurately described as cachexia, and manifests as growth failure in children with CKD. Cachexia is common and is an important risk factor for poor quality of life and increased mortality and morbidity in both adults and children with CKD. Anorexia, acidosis and inflammation are important causes of cachexia, but the underlying molecular mechanism is not well understood. Dietary intake is often poor and resting metabolic rate is increased in CKD. The energy cost of growth is increased in experimental CKD. Circulating concentrations of cytokines, such as leptin, tumor necrosis factor-alpha and interleukins 1 and 6 are increased in patients with CKD and correlate with the degree of cachexia in these individuals. We hypothesize that cytokines signal through orexigenic neuropetides such as agouti-related peptide and neuropeptide Y (NPY), and anorexigenic neuropetides such as proopiomelanocortin and alpha-melanocyte-stimulating hormone in the arcuate nucleus in the hypothalamus. This signaling system also involves the NPY receptor and the melanocortin receptors and controls appetite and metabolic rate in health and disease. Furthermore, the first order neurons of this system are located outside the blood-brain barrier and can therefore sense the circulating levels of cytokines, as well as long-term satiety hormones such as leptin and insulin and short-term satiety hormones such as ghrelin and peptide (P) YY. There is experimental evidence that this hypothalamic neuropeptide signaling system may have an important role in the pathogenesis of cachexia in CKD. Understanding the molecular mechanism of cachexia in CKD may lead to novel therapeutic strategies. SN - 0931-041X UR - https://www.unboundmedicine.com/medline/citation/15662537/Orexigenic_and_anorexigenic_mechanisms_in_the_control_of_nutrition_in_chronic_kidney_disease_ DB - PRIME DP - Unbound Medicine ER -