Orexigenic and anorexigenic mechanisms in the control of nutrition in chronic kidney disease

Robert H. Mak, Wai Cheung, Roger D. Cone, Daniel Marks

Research output: Contribution to journalArticle

66 Citations (Scopus)

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-α 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 α-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.

Original languageEnglish (US)
Pages (from-to)427-431
Number of pages5
JournalPediatric Nephrology
Volume20
Issue number3 SPEC. ISS.
DOIs
StatePublished - Mar 2005

Fingerprint

Chronic Renal Insufficiency
Cachexia
Cytokines
Leptin
Melanocortin Receptors
Hormones
Neuropeptide Y Receptors
Peptide YY
Melanocyte-Stimulating Hormones
Basal Metabolism
Pro-Opiomelanocortin
Arcuate Nucleus of Hypothalamus
Ghrelin
Neuropeptide Y
Anorexia
Appetite
Growth
Acidosis
Neuropeptides
Blood-Brain Barrier

Keywords

  • Cachexia
  • Chronic kidney disease
  • Chronic renal failure
  • Cytokines
  • Growth failure
  • Leptin
  • Melanocortin
  • Neuropeptide Y
  • Neuropeptides
  • Uremia

ASJC Scopus subject areas

  • Nephrology
  • Pediatrics, Perinatology, and Child Health

Cite this

Orexigenic and anorexigenic mechanisms in the control of nutrition in chronic kidney disease. / Mak, Robert H.; Cheung, Wai; Cone, Roger D.; Marks, Daniel.

In: Pediatric Nephrology, Vol. 20, No. 3 SPEC. ISS., 03.2005, p. 427-431.

Research output: Contribution to journalArticle

Mak, Robert H. ; Cheung, Wai ; Cone, Roger D. ; Marks, Daniel. / Orexigenic and anorexigenic mechanisms in the control of nutrition in chronic kidney disease. In: Pediatric Nephrology. 2005 ; Vol. 20, No. 3 SPEC. ISS. pp. 427-431.
@article{79a71406cf7d4107988f79ef4e409f85,
title = "Orexigenic and anorexigenic mechanisms in the control of nutrition in chronic kidney disease",
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-α 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 α-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.",
keywords = "Cachexia, Chronic kidney disease, Chronic renal failure, Cytokines, Growth failure, Leptin, Melanocortin, Neuropeptide Y, Neuropeptides, Uremia",
author = "Mak, {Robert H.} and Wai Cheung and Cone, {Roger D.} and Daniel Marks",
year = "2005",
month = "3",
doi = "10.1007/s00467-004-1789-1",
language = "English (US)",
volume = "20",
pages = "427--431",
journal = "Pediatric Nephrology",
issn = "0931-041X",
publisher = "Springer Verlag",
number = "3 SPEC. ISS.",

}

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

PY - 2005/3

Y1 - 2005/3

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-α 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 α-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.

AB - 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-α 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 α-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.

KW - Cachexia

KW - Chronic kidney disease

KW - Chronic renal failure

KW - Cytokines

KW - Growth failure

KW - Leptin

KW - Melanocortin

KW - Neuropeptide Y

KW - Neuropeptides

KW - Uremia

UR - http://www.scopus.com/inward/record.url?scp=14644411754&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=14644411754&partnerID=8YFLogxK

U2 - 10.1007/s00467-004-1789-1

DO - 10.1007/s00467-004-1789-1

M3 - Article

C2 - 15662537

AN - SCOPUS:14644411754

VL - 20

SP - 427

EP - 431

JO - Pediatric Nephrology

JF - Pediatric Nephrology

SN - 0931-041X

IS - 3 SPEC. ISS.

ER -