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Article Review/Hyperlink
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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)
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