Individualization of Immunosuppressive Therapy. II. Sirolimus as a Less Nephrotoxic Alternative to Calcineurin Inhibitors

The nephrotoxic effects of chronic administration of calcineurin inhibitors have created a demand for a potent immunosuppressive drug free of this side effect. Sirolimus (SRL) clearly displays fewer and a lesser degree of adverse effects on renal function by itself. However, in combination with calcineurin antagonists, it tends to augment the nephrotoxicity due, at least in part, to a pharmacokinetic interaction. The use of SRL for de novo immunosuppression (even with adjunctive mycophenolate mofetil) is probably not sufficient to avert alloimmune reactions. A useful combination with SRL can be achieved by reducing calcineurin inhibitor exposure by 80% for immediately functioning kidneys or by delaying its inception until renal graft recovery. SRL proffers additional benefits as an inhibitor of endothelial and smooth muscle cell proliferation, serving as the foundation of chronic immunosuppressive therapy.