Lack of effect of IGF-I on the glomerular filtration rate in non-diabetic patients with advanced chronic kidney disease.
Growth Horm IGF Res
; 19(3): 219-25, 2009 Jun.
Article
en En
| MEDLINE
| ID: mdl-19046909
ABSTRACT
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 21 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Recombinantes
/
Factor I del Crecimiento Similar a la Insulina
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Tasa de Filtración Glomerular
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Fallo Renal Crónico
Tipo de estudio:
Clinical_trials
Límite:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Growth Horm IGF Res
Asunto de la revista:
ENDOCRINOLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Reino Unido