Document Detail


Lack of effect of IGF-I on the glomerular filtration rate in non-diabetic patients with advanced chronic kidney disease.
MedLine Citation:
PMID:  19046909     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ying Kuan; Joanne Surman; Jan Frystyk; A Meguid El Nahas; Allan Flyvbjerg; John L Haylor
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2008-11-28
Journal Detail:
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:
Created Date:  2009-06-02     Completed Date:  2009-08-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9814320     Medline TA:  Growth Horm IGF Res     Country:  Scotland    
Other Details:
Languages:  eng     Pagination:  219-25     Citation Subset:  IM    
Affiliation:
Sheffield Kidney Institute, School of Medicine and Biomedical Sciences, University of Sheffield, Medical School, Sheffield, UK.
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MeSH Terms
Descriptor/Qualifier:
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:
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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