Growth hormone and insulin-like growth factor-I:A suggested role in renal transplantation and graft vessel disease

If GH and IGF-I are involved in early and probably long-term renal changes following kidney ablation, and therefore theoretically also in the series of events after a kidney transplantation, the effect of somatostatin analogue should be investigated further. Pronounced effects have been observed in a small number of reports in unilateral nephrectomy and experimental diabetes models, but until now no trials have been published on kidney transplantation models. In contrast, studies have already been performed on somatostatin analogues' effects on vascular wall changes and SMCs during vascular regeneration and in graft vessel disease. The effect of somatostatin analogues, which are potent inhibitors of GH and IGF-I production, has been investigated in short-term (octreotide and lanreotide) and long-term (octreotide only) models of uninephrectomy and diabetes both comprising early renal and glomerular growth, and subsequently an effect has been demonstrated on urinary albumin/protein excretion, a marker of kidney disease. Only octreotide inhibited the early local IGF-I accumulation and renal growth following unilateral nephrectomy in rats while lanreotide (Gronbaek et al, unpublished results) and octreotide both inhibited the renal hypertrophy after diabetes induction. Long-term octreotide studies demonstrated significant reductions in renal and glomerular growth and urinary albumin excretion in octreotide-treated control and diabetic rats, while no effect was observed in a diabetic uninephrectomized model, although using a much lower octreotide dose. Further, Igarashi et al treated uninephrectomized diabetic rats with octreotide for 3 weeks after an untreated period of 15 weeks and observed diminished kidney hypertrophy and normalization of albuminuria. It can be concluded from these studies that somatostatin analogues have pronounced effects on pathophysiological renal growth and on the development of long-term renal changes in diabetes and following uninephrectomy. As for chronic graft vessel disease and vascular growth and regeneration lanreotide has been shown to inhibit myointimal thickening following aortic or coronary balloon injury in various animal models. This effect may be partly mediated through an inhibition of vascular IGF-I production as demonstrated by Howell et al. A few studies have used a vessel allograft model and lanreotide significantly inhibited myointimal proliferation and, in addition, Hayry et al observed a decrease in IGF-I, epidermal growth factor, and platelet-derived growth factor BB following lanreotide treatment. In a rat kidney transplant model, lanreotide inhibited arterial graft myointimal thickening, however, the authors did not measure IGF-I expression. From these experiments it is hypothesized that beneficial effects of treatment with somatostatin analogues may be achieved following kidney transplantation through reducing adverse effects of GH and IGF-I on long-term changes in the transplanted kidney.