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Recombinant insulin-like growth factor-1 as a therapy for IGF-1 deficiency in renal failure

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Abstract

Renal disease in children disrupts the growth hormone (GH) and insulin-like growth factor (IGF) axis and causes growth failure. Although GH therapy stimulates growth in these children, their short stature is likely due to a form of IGF-1 deficiency (IGFD) rather than GH deficiency. Recent experimental data have caused us to reconsider the importance of IGF-1 and IGFD to human growth. Pharmacology studies in rodents, as well as studies in patients with no functional GH receptors and primary IGFD, have shown that IGF-1 is an effective growth-promoting therapy. Gene knockout studies in mice have shown that IGF-1, rather than GH, is the major hormone controlling growth. In addition, both pharmacological and genetic studies have shown that there are effects of GH and IGF-1 that require their combined presence. In children with primary IGFD, where there is no GH signaling, recombinant human (rh)IGF-1 produces a large growth response, while in children who are GH and IGF-1 deficient, treatment with rhGH is the most-appropriate therapy. Children with short stature due to renal failure are GH sufficient and have some GH receptor signaling capacity, so that rhIGF-1, or rhIGF-1 plus rhGH, are logical therapeutic options and merit clinical testing.

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  1. Tercica, 651 Gateway Boulevard, Suite 950, South San Francisco, CA 94080, USA

    Ross G. Clark

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  1. Ross G. Clark
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Correspondence to Ross G. Clark.

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This work was presented in part at the IPNA Seventh Symposium on Growth and Development in Children with Chronic Kidney Disease: The Molecular Basis of Skeletal Growth, 1–3 April 2004, Heidelberg, Germany

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Clark, R.G. Recombinant insulin-like growth factor-1 as a therapy for IGF-1 deficiency in renal failure. Pediatr Nephrol 20, 290–294 (2005). https://doi.org/10.1007/s00467-004-1714-7

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  • DOI: https://doi.org/10.1007/s00467-004-1714-7

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