Biphasic expression of IGF-I following subtotal renal ablation

Insulin-like growth factor-I (IGF-I) has been implicated in the pathogenesis of experimental renal growth. This study was designed to investigate the quantitative and qualitative changes in renal IGF-I which occur during the course of progressive renal scarring in rats submitted to extensive renal ablation. Analyses were carried out at 7, 15, 21, 30, 90 and 150 days after subtotal nephrectomy. Compensatory renal growth occurred over the first 30 days, amounting to a 161% increase in the protein content per remnant kidney (272 +/- 22 vs. 104 +/- 3 mg at the outset, p < 0.001, means +/- SD, n = 6) but DNA per remnant kidney continued to rise, reaching a 285% increase by day 90 (5.12 +/- 0.06 vs. 1.33 +/- 0.06 mg at the outset, p < 0.001), probably reflecting the continued recruitment of inflammatory cells. Changes in extractable renal IGF-I (eIGF-I) were measured by radioimmunoassay. Seven days after subtotal nephrectomy eIGF-I had increased by 70% compared with controls (2.37 +/- 0.22 ng/mg protein vs. 1.39 +/- 0.2 ng/mg at the outset, p < 0.001) but had returned to normal by 30 days. This coincided with a transient increase in the immunostainable IGF-I (iIGF-I) within the cortical collecting ducts which, again, had subsided by 30 days. However, at 90 and 150 days, as severe scarring was detected, a different pattern of immunostaining (iIGF-I) was noted. Strong staining was evident in the injured cells of the distal tubules and within the fibrosed interstitium.(ABSTRACT TRUNCATED AT 250 WORDS)