| Lack of effect of IGF-I on the glomerular filtration rate in non-diabetic patients with advanced chronic kidney disease. | |
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MedLine Citation:
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PMID: 19046909 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recombinant human insulin-like growth factor I (rhIGF-I) acutely increases the glomerular filtration rate (GFR) in human volunteers and patients with advanced chronic kidney disease (CKD). However, on chronic administration, rhIGF-I induces tolerance to its renal effects attributed to a fall in serum IGF-binding protein 3 (IGFBP-3) enhancing its systemic clearance. Tolerance may be avoided by the use of an intermittent dosage regimen of rhIGF-I. A randomised, double-blind, placebo-controlled study was undertaken in non-diabetic patients with advanced CKD to establish whether intermittent subcutaneous injections of rhIGF-I (50 microg/kg, four days/week) could increase GFR over a 24 week period and thereby have the potential to delay the onset of renal replacement therapy. Twenty-seven patients were randomised into rhIGF-I/placebo groups using a 2:1 treatment ratio. GFR was determined by inulin clearance. RhIGF-I therapy produced a sustained increase serum total and free IGF-I elevating IGFBP-1 without decreasing IGFBP-3. Inulin clearance however, was not increased after either four weeks or over the 24 week observation period. Only 4/18 rhIGF-I treated patients compared to 6/9 placebo patients completed the study, the major reason being the requirement for dialysis. Compared with healthy volunteers, advanced CKD patients had elevated serum levels of IGFBP-1, IGFBP-2, tumour necrosis factor-alpha and asymmetric dimethylarginine, all factors proposed to mediate IGF-I resistance. In conclusion, although intermittent rhIGF-I therapy elevated serum total IGF-I and prevented any fall in serum IGFBP-3, it failed to increase GFR in non-diabetic patients with advanced CKD. The lack of efficacy was attributed to the presence of renal IGF-I resistance in CKD. |
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Authors:
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Ying Kuan; Joanne Surman; Jan Frystyk; A Meguid El Nahas; Allan Flyvbjerg; John L Haylor |
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Publication Detail:
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Type: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't Date: 2008-11-28 |
Journal Detail:
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Title: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society Volume: 19 ISSN: 1532-2238 ISO Abbreviation: Growth Horm. IGF Res. Publication Date: 2009 Jun |
Date Detail:
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Created Date: 2009-06-02 Completed Date: 2009-08-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9814320 Medline TA: Growth Horm IGF Res Country: Scotland |
Other Details:
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Languages: eng Pagination: 219-25 Citation Subset: IM |
Affiliation:
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Sheffield Kidney Institute, School of Medicine and Biomedical Sciences, University of Sheffield, Medical School, Sheffield, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Double-Blind Method Female Fluorescent Antibody Technique Glomerular Filtration Rate / drug effects* Humans Injections, Subcutaneous Insulin-Like Growth Factor I / pharmacology* Kidney Failure, Acute / drug therapy Kidney Failure, Chronic / drug therapy* Male Middle Aged Placebos Recombinant Proteins / pharmacology* Treatment Failure |
| Chemical | |
Reg. No./Substance:
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0/Placebos; 0/Recombinant Proteins; 67763-96-6/Insulin-Like Growth Factor I |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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