The in vivo effect of a new, in vitro, extremely potent vitamin D3 analog KH1060 on the suppression of renal allograft rejection in the rat.
KH1060 is a new 20-epi-vitamin D3 analog, which has exerted a considerable immunosuppressive potency in vitro. We have tested in vivo the effect of KH1060 on the suppression of renal allograft rejection in the rat. Allogenic kidney transplantation from DA donor rats to Lewis recipient rats treated intraperitoneally with KH1060 in doses from 0.2 to 6 micrograms/kg/day, or saline (placebo group), or CyA 10 mg/kg/day for 10 days (positive control group), was performed. Median graft survival time in KH1060-treated groups was 7-9 days, in the placebo group 6 days, whereas CyA led to long-term graft survival, 34 days in 50% of rats and > 100 days in 50% of rats. In vivo, KH1060 failed to prolong renal allograft survival considerably, and led to development of hypercalcemia. Our results stress the existence of a large discrepancy between the in vitro and in vivo immunoregulatory effects of this vitamin D analog.
Nephrological Department, Rigshospitalet, University of Copenhagen, Denmark.
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Lewin
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Olgaard
D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D002762:Cholecalciferol / Q000031:analogs & derivatives; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000502:physiology; D016030:Kidney Transplantation / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous; D014508:Urea / Q000097:blood
D007166:Immunosuppressive Agents; C074279:KH 1060; D002762:Cholecalciferol; D016572:Cyclosporine; D014508:Urea; D003404:Creatinine; D002117:Calcitriol; D002118:Calcium