Systemic and renal hemodynamic differences between FK506 and cyclosporine in liver transplant recipients

Immunosuppression after transplantation is complicated by hypertension and nephrotoxicity, reflecting widespread vasoconstriction associated with CsA. FK506 is a novel alternative immunosuppressive agent, structurally unrelated to CsA. These studies compared systemic and renal vascular changes developing in the initial 4 weeks after liver transplantation in patients treated with FK506 (plus PRED) and CsA (plus PRED and AZA). We studied arterial pressure, cardiac index (pulsed doppler ultrasound), and systemic resistance index (SVRI) before and weekly after liver transplant in 32 patients treated with CsA (2 mg/kg initial dose plus PRED; median dose at week 4, 30 mg/day) and 14 patients treated with FK506 (0.15 mg/kg/day initial dose and PRED; mean week 4 dose, 12.5). Renal plasma flow and glomerular filtration rate (GFR) were measured by clearance of para-amino hippurate and 125-iothalamate. Renin activity, aldosterone, and urinary prostanoids were measured by RIA. Pretransplant pressures and hemodynamics reflected low SVRI and increased cardiac index typical of end-stage liver disease. After transplantation, SVRI and pressures rose in both groups, but after week 2, SVRI was lower in patients treated with FK506. This was associated with less prevalent clinical hypertension during the subsequent 4 months (4/14 FK506 (28%) vs. 25/32 (78%) CsA, P < 0.01). By contrast, renal blood flow and GFR fell in both treatment groups similarly, whereas renal vascular resistance rose. Urinary 6-keto-PG-F1-alpha was suppressed in all transplant recipients, but to a greater degree in FK506-treated patients. This value correlated directly to post-transplant GFR (r = 0.48, P < 0.001). These data indicate that FK506-based immunosuppression differs from CsA by inducing less systemic vasoconstriction and hypertension. Renal vasoconstrictive effects were at least as great as those seen with CsA, however, and indicate that nephrotoxicity will remain a common feature to both regimens.