BIPHASIC EXPRESSION OF IGF-I FOLLOWING SUBTOTAL RENAL ABLATION

Insulin-like growth factor-I (IGF-I) has been implicated in the pathog enesis of experimental renal growth. This study was designed to invest igate the quantitative and qualitative changes in renal IGF-I which oc cur during the course of progressive renal scarring in rats submitted to extensive renal ablation. Analyses were carried out at 7, 15, 21, 3 0, 90 and 150 days after subtotal nephrectomy. Compensatory renal grow th occurred over the first 30 days, amounting to a 161% increase in th e protein content per remnant kidney(272 +/- 22 vs. 104 +/- 3 mg at th e outset, p < 0.001, means +/- SD, n = 6) but DNA per remnant kidney c ontinued 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 re nal IGF-I (eIGF-I) were measured by radioimmunoassay. Seven days after subtotal nephrectomy eIGF-I had increased by 70% compared with contro ls (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. Howev er, at 90 and 150 days, as severe scarring was detected, a different p attern of immunostaining (iIGF-I) was noted. Strong staining was evide nt in the injured cells of the distal tubules and within the fibrosed interstitium. This study suggests that IGF-I may be involved both in t he early trophic response and in the later process of renal scarring t hat follows extensive renal ablation in rats.