URINARY ENDOTHELIN AND RENAL VASOCONSTRICTION WITH CYCLOSPORINE OR FK506 AFTER LIVER-TRANSPLANTATION

Transplant immunosuppression using either cyclosporine (CsA) or FK506 leads to renal vasoconstriction. To examine the role of endothelin (ET ) in this process, we measured plasma and urinary ET before and at int ervals for two years after liver transplantation. Urinary prostacyclin (as 6-keto-PG-F1 alpha), thromboxane, glomerular filtration rare and renal plasma flow were also measured. Forty-four patients were treated with CsA-based regimens and 31 patients with FK506-based regimens. Pr ednisone doses after one year were lower with FK506 (5.5 +/- 0.5 vs. 1 0.5 +/- 0.5 mg/day) by study design. Circulating plasma ET remained ab ove normal, but not different from pre-transplant levels. Urinary ET w as elevated before transplant (24.6 +/- 3.4 ng/day vs. normal 16 +/- 1 .5 ng/day, P < 0.05) and rose further after transplantation (48.5 +/- 13 ng/day, P < 0.05), remaining elevated for two years. 6-keto-PG-F1 a lpha fell from 2567 +/- 338 ng/day to subnormal levels and remained su ppressed (1158 +/- 128 ng/day, P < 0.01). Over the same period GFR fel l (84 +/- 3 ml/min to 60 +/- 3 ml/min, P < 0.01) and renal vascular re sistance index rose (11,119 +/- 561 to 23,279 +/- 1692 d.s.cm(-5).m(-2 ), P < 0.01). Similar changes were observed both with CsA and FK506-ba sed immunosuppression. No changes in ET were attributable to dihydropy ridine calcium channel blockers. These results demonstrate that urinar y ET changes independently from plasma ET after transplantation. Eleva ted ET and suppression of endothelium-derived prostacyclin persist wit h intense renal vasoconstriction for at least two years after transpla nt.