RENAL GROWTH HORMONE-INSULIN-LIKE GROWTH-FACTOR-I SYSTEM IN ACUTE-RENAL-FAILURE

The renal growth hormone-insulin-like growth factor-I system in acute ischemic renal failure. Recovery from acute tubular necrosis (ATN) is accelerated by IGF-I therapy. Furthermore, the local renal growth horm one-IGF-I system may participate in the natural repair. We examined th e IGF-I system in rat kidneys subjected to 60 minute ischemia compared to sham operated controls. Two days after injury, growth hormone rece ptor mRNA and IGF-I mRNA levels fell similar to 9 to 33% of control va lues. This was associated with a reduction in kidney immunoreactive IG F-I levels. In contrast, IGF-I receptor mRNA abundance was unchanged. However, plasma membrane IGF-I receptor binding on day 2 and day 7 was near double the control values (P < 0.01). Scatchard analysis reveale d a near twofold increase in receptor number. Since receptor mRNA leve ls were unchanged, this implies receptor protein up-regulation. In con trast to unchanged IGF-I receptor mRNA levels, the abundance of mRNA l evels of insulin-like growth factor binding proteins (IGFBP) -2, -3, - 4 and -5 fell similar to 14 to 62% of control levels day 2 after injur y (P < 0.05), suggesting reduced IGFBP production. Thus, the renal res ponse to ischemic ATN, namely, low IGFBP mRNA levels and high IGF-I re ceptor number, may function to increase IGF-I bioavailability and ther eby enhance the reparative actions of local and circulating IGF-I in i schemic ATN.