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 fa ctor-I (IGF-I) and circulating IGF-I and IGF binding proteins (IGFBPs) in early posttransplantation renal hypertrophy and overall body growt h during high-dose immunosuppression. Seven days of prednisolone and c yclosporin A (CsA) immunosuppression was administered to rats followin g unilateral nephrectomy compared with sham-operated controls. Immunos uppression of nephrectomized and control rats was followed by a reduct ion 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 kidne y 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 we re unchanged. In a supplementary study separating the effects of the t wo 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 wit h prednisolone and CsA was followed by less kidney IGF-I accumulation and compensatory renal growth compared with placebo treatment. In addi tion, a sustained increase in circulating levels of IGFBP-3 and 30-kd IGFBPs was observed, which may be involved in the growth impairment ob served following immunosuppressive treatment. Copyright (C) 1998 by W. B. Saunders Company.