Abstract
Chronic kidney disease (CKD) in children is associated with dramatic changes in the growth hormone (GH) and insulin-like growth factor (IGF-1) axis, resulting in growth retardation. Moderate-to-severe growth retardation in CKD is associated with increased morbidity and mortality. Renal failure is a state of GH resistance and not GH deficiency. Some mechanisms of GH resistance are: reduced density of GH receptors in target organs, impaired GH-activated post-receptor Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling, and reduced levels of free IGF-1 due to increased inhibitory IGF-binding proteins (IGFBPs). Treatment with recombinant human growth hormone (rhGH) has been proven to be safe and efficacious in children with CKD. Even though rhGH has been shown to improve catch-up growth and to allow the child to achieve normal adult height, the final adult height is still significantly below the genetic target. Growth retardation may persist after renal transplantation due to multiple factors, such as steroid use, decreased renal function and an abnormal GH–IGF1 axis. Those below age 6 years are the ones to benefit most from transplantation in demonstrating acceleration in linear growth. Newer treatment modalities targeting the GH resistance with recombinant human IGF-1 (rhIGF-1), recombinant human IGFBP3 (rhIGFBP3) and IGFBP displacers are under investigation and may prove to be more effective in treating growth failure in CKD.
Highlights
Growth retardation is a common result of chronic kidney disease (CKD) in childhood
Even though the growth failure was correlated with the degree of renal impairment, those with mild reduction of glomerular filtration rate (GFR) exhibited short stature
Children were short at initiation of dialysis, with younger age associated with more severe growth failure and little improvement in height
Summary
Growth retardation is a common result of chronic kidney disease (CKD) in childhood. Children with CKD fail to achieve the final adult height consistent with their genetic potential [1]. Random fasting serum levels of GH are normal or increased in children and adults with CKD, depending on the extent of renal failure. The other adverse effect of the use of rhIGF-1 observed in GH receptor-deficient patients is hypoglycemia, due to low levels of IGFBP3 and increased level of free IGF-1 available for binding to insulin receptors [32]. Animal studies in hypophysectomized rats and dwarf dw/dw rats treated with IGFBP displacers demonstrated increased kidney size, improved renal function, and the stimulation of weight gain and bone growth. This effect was enhanced when treatment with IGFBP displacers was combined with rhIGF-1 [37]. While whole-body growth in uremic rats was similar with treatment with either agent, an additive effect on longitudinal growth and anabolism was demonstrated when both agents were administered together [35]
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