Influence of cyclosporin, tacrolimus and rapamycin on renal function and arterial hypertension after renal transplantation

Cyclosporin and tacrolimus have improved survival figures in organ transpla ntation. However, both drugs are potentially nephrotoxic. The immunosuppres sive and nephrotoxic effects of both drugs appear to depend on the inhibiti on of calcineurin. Cyclosporin and tacrolimus cause acute (functional chang es) and chronic nephrotoxicity (structural lesions in the kidney). These la st important lesions include arteriolar hyalinosis, stripped interstitial f ibrosis and tubular atrophy. It is possible that repeated episodes of renal ischaemia contribute to the development of chronic nephrotoxicity and then chronic allograft nephropathy. Cyclosporin and tacrolimus also induce arte rial hypertension. Therefore, the beneficial effects of immunosuppression h ave been limited due to nephrotoxicity and arterial hypertension. Rapamycin , a novel immunosuppressive agent, that does not inhibit calcineurin, provi des immunosuppression without nephrotoxicity. In fact, in the trials perfor med in Europe, sirolimus-treated immunosuppression patients exhibited a muc h better renal function than cyclosporin-treated patients. However, siroiim us can potentiate the nephrotoxic effect of cyclosporin. Therefore, when cy closporin and sirolimus are used in combination, a reduction of the cyclosp orin dose is desirable.