Atrophy or hypertrophy in chronic renal ischemia: role of the IGF-I system

To examine the role of insulin-like growth factor–1 (IGF-1) in renal atrophy of rats with two-kidney, one-clip (2K1C), in which the clipped kidney atrophies, and in the one-kidney, one-clip (1K1C) model of renovascular hypertension, in which it hypertrophies, we studied levels of IGF-I, mRNA, and protein in 2K1C, 1K1C, and unilateral nephrectomy (NPX) in rats by solution-hybridization RNase protection, and radioimmunoassay, respectively, both cross-reactively and longitudinally at 3, 10, and 30 days after clipping. Three days after clipping, there were no differences in blood pressure or kidney size; however, 10 and 30 days postoperation, the clipped kidney shrank in the 2K1C model. The nonclipped 2K1C and the clipped 1K1C and unilateral nephrectomy kidneys increased in weight (P< .05. At day 3 the IGF-I levels were lower (557 ± 54, 335 ± 61 ng/g in control and clipped 2K1C, P< .05, v 1074 ± 186, 1109 ± 54, and 1154 ± 200 ng/g kidney, nonclipped 2K1C, 1K1C, and NPX, respectively). At 30 days the IGF-I levels were 300 ± 24 ng/g in control (P< .05) v clipped 2K1C, 160 ± 19, 218 ± 20 ng/g in nonclipped 2K1C and 406 ± 33 and 470 ± 34 ng/g in 1K1C and NPX, respectively (P< .05) v control and clipped 2K1C. Kidney mRNA was increased in the clipped 2K1C. In conclusion, the kidney that had higher IGF-I levels early in nonclipped 2K1C, 1K1C, and nephrectomy hypertrophied, and the kidney (clipped 2K1C) that failed to increase IGF-I atrophied. IGF-I levels are dissociated from the local mRNA message.