THE PATHOPHYSIOLOGY OF SANDIMMUNE (CYCLOSPORINE) IN MAN AND ANIMALS

Part I: The side-effects of Sandimmune that have been of most significance clinically are renal dysfunction, renal vascular damage and arterial hypertension. To examine the nature and the origin of such effects, the actions of Sandimmune on the renal tubule, the renal vessels and systemic vessels have been analyzed. To evaluate whether common vasoconstrictory systems may be involved, changes in the renin-angiotensin-aldosterone system and prostaglandin-thromboxane system have been assessed. Comparison between animal and human data obtained in vivo and in vitro shows the actions of Sandimmune on the renal tubule to be modest and involve only a few specific effects. The major action of Sandimmune is on the vessels, vasoconstriction being the major cause of renal dysfunction and also the cause of arterial hypertension. Neither the circulating renin-angiotension-aldosterone system nor the prostaglandin-thromboxane system is clearly responsible for vasoconstriction. Although not itself a vasoconstrictor, Sandimmune seems to modulate the constrictory and dilatory response to other agents in several vascular beds.