The multiple functions of insulin-like growth factor 1 in kidney disease

Unilateral nephrectomy (Uni-Nx) produces compensatory hypertrophy of the remnant kidney. In this anabolic process, the upregulation of renal insulin-like growth factor 1 (IGF-1) plays a key role, which has inspired numerous studies considering the potential regenerative actions of the IGF-1 and the subsequent increase in the glomerular filtration rate. Thus, IGF-1 administration has shown to be able to induce renal hypertrophy, increase glomerular size and enhance glomerular filtration rate, without reaching glomerulosclerosis. Moreover, protein uptake also contributes to renal hypertrophy by increasing renal and circulating IGF-1 levels. In this respect, circulating IGF-1 concentration has been used as a marker of the nutritional status in end-stage CKD patients and has been associated with hormones that participate in the regulation of appetite. Moreover, IGF-1 regulate mineral metabolism, participating in phosphate resorption and calcitriol production by increasing 1-α-hydroxylase activity. Furthermore, IGF-1 is key for bone growth in pediatric patients, acting directly in chondrocytes, osteoblasts and, in a lesser manner, in osteoclasts. In addition, IGF-1 is an important inductor of erythroid proliferation, being able to maintain erythrocytic homeostasis in anephric patients. Nevertheless, the actions of the IGF-1 are attenuated in the context of renal disease, which may be promoted by the presence of inhibitory factors, such as the IGF binding proteins, and inability to trigger intracellular downstream signaling despite of normal IGF-1 receptor expression in cell surface. This review highlights the importance of the IGF-1 in the context of CKD and its potential contribution to renal and also systemic disorders.