ROLE OF STEROID DOSE IN HYPERTENSION EARLY AFTER LIVER-TRANSPLANTATION WITH TACROLIMUS (FK506) AND CYCLOSPORINE

Transplant immunosuppression using either cyclosporine (CsA) or tacrol imus (FK506) leads to renal vasoconstriction and nephrotoxicity. Despi te producing similar effects within the kidney and blood vessels, clin ical hypertension occurs less frequently with tacrolimus during the fi rst year after transplantation, compared with CsA. To examine the role of steroid dose in early posttransplant hypertension, we measured blo od pressure and kidney function in liver transplant recipients treated with tacrolimus and either high-dose (TAC-HI-P, n = 19) or low-dose ( TAC-LO-P, n = 20) prednisone, compared with CsA-treated recipients (n = 29) receiving prednisone doses similar to the TAC-HI-P group. At 1 m onth, hypertension occurred more often with CsA (72%) than with TAC-HI -P (42%, P < 0.05) or TAC-LO-P (30%, P < 0.05). By 4 months after tran splantation, hypertension developed in nearly twice as many TAC-HI-P ( 63%) as TAC-LO-P patients (32%, P < 0.05), with no difference between TAC-HI-P and CsA (86%, NS). Daily prednisone dose at 1 month closely p aralleled cumulative steroid dose in the first month in the TAC-HI-P a nd TAC-LO-P groups. Fourteen of 19 TAC-HI-P patients (74%) required bo lus steroids for treatment of rejection within the first month, compar ed with 3/20 (15%) TAC-LO-P and 10/29 (34%) CsA recipients. Glomerular filtration rate fell from pretransplant levels at 1 month and 4 month s to the same degree in CsA, TAC-HI-P, and TAC-LO-P patients. These re sults demonstrate a central role for steroid dose in the rate of onset of hypertension early after liver transplantation using tacrolimus im munosuppression. Both daily dose and cumulative dosage, including bolu s treatment for rejection, may impact on the development of hypertensi on. Since prevalence rates rise to levels comparable to CsA by 24 mont hs regardless of steroid dose, hypertension after liver transplant may be mediated by different mechanisms at different stages of the posttr ansplant course.