Nephrotoxicity of FK-506 in the rat. Studies on glomerular and tubular function, and on the relationship between efficacy and toxicity
| Autor: | Kemp E, Dieperink H, Finn Thomsen Nielsen, Starklint H, Leyssac Pp |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Graft Rejection
Male medicine.medical_specialty Renal glomerulus Metabolic Clearance Rate Kidney Glomerulus Drinking Renal function Urination Pharmacology Lithium Kidney Tacrolimus Nephrotoxicity Kidney Tubules Proximal Rats Sprague-Dawley Eating Internal medicine Cyclosporin a medicine Animals Transplantation Inulin Clearance Dose-Response Relationship Drug business.industry Body Weight Inulin Skin Transplantation Rats medicine.anatomical_structure Endocrinology Nephrology Rats Inbred Lew Renal physiology Toxicity business Glomerular Filtration Rate |
| Zdroj: | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 10(3) |
| ISSN: | 0931-0509 |
| Popis: | Recent studies in liver and kidney transplant recipients revealed a nephrotoxic adverse effect of the new macrolide immunosuppressant FK-506. Therefore the effect of FK-506 0.1 to 0.8 mg per kg per day was investigated in rats using clearance methods including lithium clearance. In rats given FK-506 or placebo during 1 week the nephrotoxicity of FK-506 was characterized by a slight reduction of inulin clearance. The end proximal delivery as measured by the lithium clearance was decreased by FK-506. In rats treated for 4 weeks with FK-506 0.8 mg/kg/day the glomerular filtration rate (GFR) had decreased to 23% of the GFR found in controls (P < 0.001), while end proximal delivery was only 8% of normal. Renal histopathological investigation showed a slight but statistically significant increase of tubular basophilia and atrophy in FK-506-treated rats. Skin transplantation studies in the same rat strain showed a dose-dependent immunosuppressive effect of FK-506. FK-506 0.8 mg/kg was significantly more immunosuppressive than 0.2 or 0.4 mg/kg, so it was concluded that the lower doses of FK-506 did not fully exploit the drug's immunosuppressive potential. Thus in a dosage inside the therapeutic range defined from skin transplantations, FK-506 generated a number of toxic effects including a considerable nephrotoxic effect. The FK-506 induced changes in glomerular and tubular function was a close match to the changes found in cyclosporin A nephrotoxicity. The present study suggests that FK-506 nephrotoxicity is caused by constriction of preglomerular vessels. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|