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Growth and GH–IGF in Chronic Kidney Disease

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Handbook of Growth and Growth Monitoring in Health and Disease

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Abstract

Growth failure in chronic kidney disease (CKD) is multifactorial and has been correlated with increased hospitalizations, increased mortality rates, and decreased quality of life measures. Perturbations in the growth hormone (GH)–insulin-like growth factor (IGF)-I axis contribute to the poor linear growth in infants, children, and adolescents with CKD but have also been suggested to affect kidney disease progression. In general, GH levels are increased due to loss of nephron mass, reduced renal clearance, and an increase in the half-life. The normal pulsatile secretion of GH is disrupted in CKD and is replaced by a more tonic pattern that is less effective in promoting tissue growth. Thus, renal failure can be characterized as a state of GH resistance and not a state of GH deficiency. GH resistance can be attributed to reduced density of GH receptors on target tissues, impaired post-receptor Janus kinase/signal transducer, and activator of transcription (JAK/STAT) signaling leading to decreased transcription of GH-dependent genes, such as IGF-I. Increased levels of IGF-binding proteins (IGFBPs) along with the reduced IGF-I levels lead to reduced bioavailability of free IGF-I at the target tissue. IGF-I is a key mediator of the somatic effects of GH and the reduced levels correlate with the height deficit observed in children with CKD. Ultimately the goal is for children with CKD to achieve their full genetic height potential. Significant efforts have been taken to improve final adult heights in chronic kidney disease (CKD), end-stage renal disease, and after renal transplantation. These efforts include correcting the metabolic acidosis, improving nutrition, reversing hyperparathyroidism, minimizing corticosteroid use, and administering recombinant human GH (rhGH) therapy. Administration of supraphysiologic doses of rhGH has been shown to overcome the GH resistance and improve growth velocity and in certain circumstances can accelerate growth velocity above the normal rate (catch-up growth) but this effect may not be long lasting. Targeting alternative pathways in the GH–IGF axis may prove efficacious in the long-term treatment of growth failure in children with CKD.

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Abbreviations

ALS:

Acid-labile subunit

CKD:

Chronic kidney disease

ERK:

Extracellular receptor kinase

GH:

Growth hormone

GHBP:

Growth hormone-binding protein

GHR:

Growth hormone receptor

IGF:

Insulin-like growth factor

IGFBP:

Insulin-like growth factor-binding protein

JAK:

Janus kinase

MAPK:

Mitogen-activated protein kinase

PI3K:

Phosphoinositide 3-kinase

rhGH:

Recombinant human growth hormone

SOCS:

Suppressors of cytokine signaling

STAT:

Signal transducer and activator of transcription

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Authors and Affiliations

  1. University of California San Diego Rady Children’s Hospital, San Diego, CA, 92123, USA

    Elizabeth Ingulli

  2. School of Medicine, Stony Brook University Medical Center, 11794, Stony Brook, NY, USA

    Richard Fine

  3. Division of Pediatric Nephrology, University of California, 92093-0634, San Diego, CA, USA

    Robert Mak

Authors
  1. Elizabeth Ingulli
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  2. Richard Fine
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  3. Robert Mak
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Corresponding author

Correspondence to Elizabeth Ingulli .

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Editors and Affiliations

  1. Dept. Nutrition & Dietetics, King's College, Stamford St. 150, London, SE1 9NH, United Kingdom

    Victor R. Preedy

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Ingulli, E., Fine, R., Mak, R. (2012). Growth and GH–IGF in Chronic Kidney Disease. In: Preedy, V. (eds) Handbook of Growth and Growth Monitoring in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1795-9_164

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  • DOI: https://doi.org/10.1007/978-1-4419-1795-9_164

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