Effect of immunosuppression on kidney and serum insulin-like growth factor-I (IGF-I), IGF binding proteins, and renal growth following unilateral nephrectomy in rats.
A rat model was used to study the role of renal insulin-like growth factor-I (IGF-I) and circulating IGF-I and IGF binding proteins (IGFBPs) in early posttransplantation renal hypertrophy and overall body growth during high-dose immunosuppression. Seven days of prednisolone and cyclosporin A (CsA) immunosuppression was administered to rats following unilateral nephrectomy compared with sham-operated controls. Immunosuppression of nephrectomized and control rats was followed by a reduction in body weight (BW) compared with placebo treatment. In addition, immunosuppression inhibited kidney IGF-I accumulation and compensatory renal growth in uninephrectomized rats, but caused no change in kidney weight or IGF-I levels in control rats. Immunosuppression induced a sustained significant increase in circulating IGFBP-3 and 30-kd IGFBPs in uninephrectomized and controls rats, whereas serum IGF-I levels were unchanged. In a supplementary study separating the effects of the two immunosuppressants, the kidney IGF-I changes and renal growth were primarily affected by CsA, while the changes in IGFBPs appeared to be caused by prednisolone treatment. In conclusion, immunosuppression with prednisolone and CsA was followed by less kidney IGF-I accumulation and compensatory renal growth compared with placebo treatment. In addition, a sustained increase in circulating levels of IGFBP-3 and 30-kd IGFBPs was observed, which may be involved in the growth impairment observed following immunosuppressive treatment.
Institute of Experimental Clinical Research, Aarhus University Hospital, Denmark.
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Grønbaek
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Skjaerbaek
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Orskov
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Flyvbjerg
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D004435:Eating / Q000187:drug effects / Q000276:immunology; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000254:growth & development* / Q000276:immunology*; D008297:Male; D009392:Nephrectomy; D009929:Organ Size / Q000187:drug effects / Q000276:immunology; D011239:Prednisolone / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar
D007166:Immunosuppressive Agents; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D016572:Cyclosporine; D011239:Prednisolone