Cyclosporin and organ specific toxicity: clinical aspects, pharmacogenetics and perspectives

Cyclosporine (CsA) has considerably modified the graft survival in solid organ and bone marrow transplantations. It is also the treatment of choice in chronic diseases such as steroid resistance and/or dependence nephrotic syndrome and autoimmune-diseases, especially in those cases that require long term treatments. Renal toxicity is the major adverse effect of chronic CsA administration. Deterioration of renal function and renal histopathology are the basic elements of the diagnosis. Overall, available studies suggest a good degree of safety related to appropriate drug dosages even if they require an adequate degree of surveillance in case of rapid changes of renal functions and long term evaluation of renal pathology. CsA neurotoxicity is the second major problem that seems underestimated especially in case of subtle manifestations in children. The full blown picture of the acute form is characterized by convulsion and sudden alteration of mental function that are reversible upon drug withdrawal. The diagnosis is based on typical CT and MRI aspects of extensive bilateral white-matter abnormalities in the occipital region of the brain that mimics the posterior encephalopathy syndrome. Prospective evaluations of drug tolerance include renal histology in case of chronic renal toxicity and neuro-imaging to identify and block acute neurotoxicity.