Chronic cyclosporine nephrotoxicity

Cyclosporine has improved patient and graft survival rates in solid organ transplantation, and has been increasingly applied with considerable clinical benefit in the treatment of autoimmune diseases. However, the therapeutic benefits of immunosuppressive therapy for transplant and autoimmune indications have frequently been limited by the occurrence of chronic nephrotoxicity. Cyclosporine nephrotoxicity therefore remains an important clinical challenge. The clinical aspects and pathophysiology of chronic cyclosporine nephrotoxicity, which is characterized by a decrease in glomerular filtration rate, afferent arteriolopathy, and striped tubulointerstitial fibrosis, are reviewed. Insights gained from experimental models of chronic nephrotoxicity associated with tubulointerstitial fibrosis are presented to elucidate the pathophysiology.