Forty years of cyclosporine in clinical practice

Abstract

Cyclosporine (CsA) was discovered in the lab of Sandoz in Switzerland in 1972. while searching for an antifungal drug. However, it quickly became an irreplaceable immunosuppressive drug for renal and other solid organ transplantation. It has been found, in the initial experiments, that CsA inhibits both in vitro cell-mediated lysis and lymphocyte sensitization by allogeneic target cells. Clinical trials have demonstrated better one-year graft survival after cadaveric renal transplants when receiving CsA instead of azathioprine. Although improvement has been observed in the rates of one-year renal graft survival and acute rejection, but long-term graft survival rate did not improve. This can be attributed to the nephrotoxic effects of the CsA. This issue is a consequence of hemodynamic effects on renal blood flow and glomerular filtration, effect on renal tubular function and blood vessels. Along with nephrotoxicity, CsA also causes other adverse effects such as hypertension, gingival hyperplasia, hyperkalemia, hypomagnesemia, hyperlipidemia, neurotoxicity, and in some cases thrombotic microangiopathies. However, in recent years CsA nephrotoxicity has been looked at from a different angle, where it has been linked to high CsA doses that used to be administered. Following its use in solid organ transplantation, CsA has been found to have an important role in treating systemic connective tissue diseases, as well as its consequences, primary glomerulonephritis, inflammatory bowel disease, and psoriasis. CsA effectiveness in treating above mentioned diseases is still greater than its side effects, which makes it a base of treatment options for numerous diseases.