Insulin-like growth factor-I ameliorates delayed kidney graft function and the acute nephrotoxic effects of cyclosporine.

Abstract

BACKGROUND:

Delayed graft function (DGF) is a relatively common complication after cadaveric renal transplantation. The adverse effect of DGF on long-term graft survival has lead to intensive efforts to reduce ischemic graft injury. In this study we examined the effects of a new protective treatment based on insulin growth factor (IGF)-I. We evaluated the impact of the treatment on renal recovery and on the nephrotoxicity that is a common side effect of mainstream immunosuppressants. Because therapy with IGF-I or the analog des(1-3)IGF-I is effective in treating experimental ischemic renal failure, these peptides may be useful as perspective clinical treatments.

METHODS:

We have addressed three areas relating to the potential use of IGF-I and its analog des(1-3)IGF-I. First, because of the immunogenic properties of IGF-I, we assessed the effect of des(1-3)IGF-I on the rejection of skin allografts in Lewis rats. Next we determined whether treatment with des(1-3)IGF-I influences the early function of transplanted kidneys in a model of DGF induced by a combination of warm and cold ischemia. Finally we tested whether IGF-I protects against acute cyclosporine nephrotoxicity.

RESULTS:

Des(1-3)IGF-I did not accelerate the rejection of the skin grafts (P=0.57). The administration of this peptide in a model of syngenic renal transplant improved the early function of the graft. Postoperative values of creatinine and blood urea nitrogen were significantly better (P<0.05) in treated animals. IGF-I also ameliorated the nephrotoxicity of cyclosporine, with better values of creatinine and blood urea nitrogen (P<0.05).

CONCLUSIONS:

In evaluating this study it should be recognized that the animal models studied, although widely used, differ from the human condition. However, IGF-I and des(1-3)IGF-I exhibit properties that strongly suggest their value in preventing clinical DGF, and they deserve further studies.

• Authors: M Maestri, D C Dafoe, G A Adams, A Gaspari, F Luzzana, F Innocente, J Rademacher, P Dionigi, A Barbieri, F Zonta, A Zonta, R Rabkin
• Journal: Transplantation (Transplantation) Vol. 64 Issue 2 Pg. 185-90 (Jul 27 1997) ISSN: 0041-1337 [Print] United States
• PMID: 9256171 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Peptide Fragments
• insulin-like growth factor 1, des-(1-3)-
• Insulin-Like Growth Factor I
• Cyclosporine

Topics

• Animals
• Cyclosporine (toxicity)
• Drug Synergism
• Graft Rejection (prevention & control)
• Insulin-Like Growth Factor I (pharmacology, therapeutic use)
• Kidney Diseases (chemically induced)
• Kidney Transplantation (immunology, physiology)
• Peptide Fragments (pharmacology)
• Rats
• Rats, Inbred Lew
• Rats, Inbred WF
• Transplantation, Homologous (immunology)