title: Long-term maintenance of therapeutic cyclosporine levels leads to optimal graft survival without evidence of chronic nephrotoxicity.
abstract: Since the introduction of cyclosporine into clinical use, a major area of concern within the transplant community has been the fear of chronic nephrotoxicity. Although progressive renal damage does appear to occur in native kidneys of heart and liver transplant patients receiving cyclosporine, it has been our contention that its use is not a major cause of deterioration in renal allografts. We therefore undertook a study of 91 consecutive renal transplants performed over a three-year period with a minimum graft survival of 1 year and a follow-up of 7-9 years. Serial serum creatinine values, iothalamate clearances and cyclosporine levels were obtained at 3 months after transplantation and yearly thereafter. Biopsies were performed on all grafts that had failed as well as on the majority of patients with deteriorating renal function, and were interpreted by two nephropathologists. As measured by iothalamate clearances, 65% of the patients in this series exhibited absolutely stable renal function despite the maintenance of cyclosporine levels of more than 200 ng/ml for 7-9 years. Since these stable patients did not reveal any decline in renal function, it therefore follows that they did not experience chronic cyclosporine nephrotoxicity. Furthermore, none of the patients with declining renal function or with failed grafts showed any evidence of nephrotoxicity on biopsy. Chronic cyclosporine nephrotoxicity may be a cause of declining function or graft loss with renal transplant recipients, but if so, it is exceedingly rare.
authors.affiliation: Department of Surgery, Baystate Medical Center, Tufts University School of Medicine, Springfield, MA 01199, USA.
authors.forename: G S
authors.initials: GS
authors.lastname: Lipkowitz
authors.forename: R L
authors.initials: RL
authors.lastname: Madden
authors.forename: J
authors.initials: J
authors.lastname: Mulhern
authors.forename: G
authors.initials: G
authors.lastname: Braden
authors.forename: M
authors.initials: M
authors.lastname: O'Shea
authors.forename: J
authors.initials: J
authors.lastname: O'Shaughnessy
authors.forename: S
authors.initials: S
authors.lastname: Nash
authors.forename: A
authors.initials: A
authors.lastname: Kurbanov
authors.forename: J
authors.initials: J
authors.lastname: Freeman
authors.forename: H
authors.initials: H
authors.lastname: Rennke
authors.forename: M
authors.initials: M
authors.lastname: Germain
mesh_terms: D003401:Creatine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007483:Iothalamic Acid / Q000493:pharmacokinetics; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D016030:Kidney Transplantation; D008297:Male; D008657:Metabolic Clearance Rate; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D007483:Iothalamic Acid; D016572:Cyclosporine; D003401:Creatine