HDCN Article Review/Hyperlink

Fervenza FC, Maidment H, Ike J, Hintz R, Liu F, Bloedow DC, Hoffman AR, Gesundheit N

Pharmacokinetics of insulin-like growth factor in advanced chronic renal failure

Kidney Int (Apr) 49:1134-1140 1996

This paper reports the pharmacokinetics of recombinant Insulin-like Growth Factor-1 (IGF-1) in 6 CRF non dialyzed patients, compared to 6 healthy volunteers and extends the previous published study in maintenance dialysis patients by Fouque et al (Kidney Int 1995;47:869-875). One dose of rhIGF-1 (80 g/kg) was administered subcutaneously in the triceps area. The subjects were fed just after the administration of rhIGF-1. Blood samples were taken for 24 hr.

The results show that there is no accumulation of the compound in CRF patients compared to healthy volunteers. Serum IGF-1 peaks at about 4 to 5 hours after SC injection. The volume of distribution is reduced in CRF patients, explaining the higher peak value in CRF patients (720 vs 530 ng/ml, p <0.05). The endogenous production of IGF-1 derived from the pharmacokinetic parameters is also similar to that of normal adults (40 g/kg/d) and in the range reported by Fouque et al.

The IGF binding protein system is fully described, including a protease assay. It is shown that: 1) serum BP3 is elevated compared to normals (a 30% increase) and constant throughout the day after receiving the IGF-1 injection 2) small mol weight BPs (BP4, BP1 and BP2 presumably) are increased in CRF patients (as noticed in J Am Soc Nephrol 1995;6:1427-1433) 3) a binding protein protease fragment is present (28-30 kD) and has affinity for BP3 antibody 4) there is no increase in protease activity, suggesting that the presence of protease fragments is mostly due to a reduced renal clearance. The techniques used in this paper may be considered as the reference methods for the IGF-1/IGF binding proteins in chronic renal failure.

Therefore, recombinant IGF-1 dose not accumulate in CRF in the short-term. The amount used here is in the usual range given during clinical studies, i.e. 40 to 100 g/kg per injection. The usual frequency of administration is every 12 hours. Side-effects are not uncommon and include hypoglycemia, hypokalemia, tachycardia, dizziness, and headache.

Comment: A number of studies are under way in chronic and acute renal failure to delineate the future indications of this strong anabolic factor which also improves recovery in experimental acute renal failure. (Denis Fouque, M.D., University of Lyons, France)