Hazards of cyclosporine a therapy and recommendations for its use

Abstract Cyclosporine nephrotoxicity represents a new type of drug-toxicity. Morphologic lesions occur in both the tubular and vascular system. Cyclosporine nephrotoxicity is dose-dependent. At therapeutic drug levels only functional changes occur consisting of a reduction of glomerular filtration rate and renal plasma flow. Superimposed on the functional toxicity are morphologic changes which may result in severe cases in acute or chronic renal failure. The threshold for the development of cyclosporine nephrotoxicity depends on drug-blood-levels, individual sensitivity to cyclosporine and the presence of concurrent risk factors. Based on the experience with the drug the following recommendations are made for clinical use especially in patients with autoimmune diseases: the initial dose should not exceed 5 mg/kg body weight; the dose should be reduced if blood cyclosporine levels are over 400 ng/ml; in addition, a dose reduction is recommended if serum creatinine values exceed 30% of pretreatment values or if other signs of cyclosporine toxicity, such as hepatoxicity, hypertension, etc. occur. By strict adherence to these suggestions it should be possible to treat patients for a prolonged period with cyclosporine without irreversible morphologic lesions.