Nephrotoxicity of Cyclosporin a in Liver and Kidney Transplant Patients

Abstract

SummaryIn six of twelve orthotopic liver recipients nephrotoxicity was noted after 13-22 days of treatment with 16.3±2.9 (SEM) mg/kg per day of cyclosporin A (CyA). With a decrease in the daily CyA dose to 9.2±2.3 (SEM) mg/kg kidney function returned to normal. No hepatic rejections occurred on this lowered CyA dose. In 4 out of 66 kidney recipients a switch from a CyA dose of 5.2-10.7 mg/kg daily to azathioprine was done 4-8 months after transplant because of unsatisfactory kidney function, suspected to be due to nephrotoxicity. In three patients, this resulted in an improved graft function. A fourth transplant was lost to an irreversible rejection 13 days later. Thus CyA is nephrotoxic but this toxicity is easily reversed, even after many months of treatment, and the ease with which this complication can be managed suggests that nephrotoxicity should not diminish the high expectations that transplant surgeons have for CyA.

Pharmacogenomics and personalized medicine: a review focused on their application in the Chinese population

“…However, its use is limited by significant adverse side effects, in particular, acute and chronic calcineurin inhibitor nephrotoxicity [38,39] and high variety in bioavailability, which can range from 5% to 89% [40] . Because cyclosporine A has a narrow therapeutic index and marked interindividual pharmacokinetic variation, its usage requires monitoring the drug concentration to ensure that it is within the recommended therapeutic range.…”

Open Trial of Cyclosporine in Patients with Severe Active Crohn's Disease Refractory to Conventional Therapy

“…Cyd osporine was administered for 16 weeks at the end of which it was tlisco ntinucd witho ut tapering. The 16 week period was chosen following the design and results of previous C rohn's d isease studies ( 1,23) and because o f the known reversihiliry of renal sitle effects after sho rt term use of cyclosporinc (24,25). Patients were seen regularl y during and after cyclosporinc therapy and their C ro hn's disease course to relapse d ocumented.…”

Immunosuppression and Other Nonsurgical Factors in the Improved Results of Liver Transplantation

“…In retrospect, part of the problem was failure to distinguish rejection from drug toxicity. 29 Nevertheless, many subsequent reports, including our own, 29,35,36 have shown that nephrotoxicity is the most limiting side effect of cyclosporine.…”

“…In retrospect, part of the problem was failure to distinguish rejection from drug toxicity. 29 Nevertheless, many subsequent reports, including our own, 29,35,36 have shown that nephrotoxicity is the most limiting side effect of cyclosporine.The full exploitation of the drug was not possible without combining it with other agents, of which prednisone was the most important. 29,36 By this polypharmacy approach, it was possible to control rejection better even though smaller and less nephrotoxic doses of cyclosporine were used.…”