Insulin-like Growth Factor (IGF-I) in Hemodialysis Patients

The purpose of this study is to investigate whether the anabolic potentials of insulin may be used to reverse the catabolic effects of hemodialysis in non-diabetic patients with end-stage renal failure.

Nutritional markers such as lean body mass and serum albumin are strong predictors of the mortality and morbidity in patients with end-stage renal failure (ESRF) on maintenance hemodialysis (HD). Maintenance HD is considered to contribute to the malnutrition of patients with ESRF, but the exact mechanism has remained unknown. However, we have recently shown that the bioactivity of insulin-like growth factor-I (IGF-I) is reduced by 50% during HD. Furthermore, we showed that the reduction in the bioactivity of IGF-I is directly linked to an up-regulation of IGF-binding protein-1 (IGFBP-1), the only acutely regulated IGFBP, which increased by 6-fold during HD. IGFBP-1 is produced in the liver, primarily under the control of insulin, which promptly inhibits the hepatic production of IGFBP-1. As plasma insulin remains fairly low during a maintenance HD, the increase in IGFBP-1 may be explained by the absence of insulin. The finding that HD acutely down-regulates the bioactivity of IGF-I by an up-regulation of IGFBP-1 may not only explain the catabolic mechanisms of HD per se, it also opens for a new treatment strategy of ESRF patients undergoing maintenance HD. Thus, on the basis of our previous study we hypothesize that treatment of ERSF patients with high doses of insulin during maintenance HD may counter-act the HD-induced stimulation of IGFBP-1, making it possible to preserve the bioactivity of IGF-I, and thereby abolishing the catabolic impact of HD.

Dialysis, Malnutrition, Insulin-Like Growth Factor I, Insulin-Like Growth Factor Binding Protein 1, Inflammation

All patients are randomly assigned to a hemodialysis session with either i) no infusion, ii) a continuous iv infusion of glucose, and iii) a continuous iv infusion of glucose and shortacting insulin. Each dialysis session will be separated by 2 weeks of wash-out

Relationship between inflammatory markers and plasma concentrations of IGF-I and IGFBP-1 during hemodialysis

Inclusion Criteria: > 18 years stable patients on maintenance hemodialysis for > 3 months well-functioning arteriovenous (AV) shunt with recirculation < 5% informed consent Exclusion Criteria: diabetes mellitus body mass index < 18.5 kg/m2 or > 30 kg/m2 malnutrition (subjective global assessment (SGA) score C) malignancy use of immunosuppressive drugs including glucocorticosteroids severe infectious disease < 4 weeks pregnancy Exclusion Criteria during the study: myocardial infarction or arrythmia with hemodynamic derangements permanent thrombosis in the arteriovenous (AV) shunt severe infectious disease renal transplantation

Reinhard M, Frystyk J, Jespersen B, Bjerre M, Christiansen JS, Flyvbjerg A, Ivarsen P. Effect of hyperinsulinemia during hemodialysis on the insulin-like growth factor system and inflammatory biomarkers: a randomized open-label crossover study. BMC Nephrol. 2013 Apr 4;14:80. doi: 10.1186/1471-2369-14-80.